Analysis of cumulative live birth rate outcomes of three controlled ovarian hyperstimulation protocols in patients with diminished ovarian reserve following laparoscopic cystectomy of ovarial endometrioma: A retrospective cohort study

Analysis of cumulative live birth rate outcomes of three controlled ovarian hyperstimulation protocols in patients with diminished ovarian reserve following laparoscopic cystectomy of ovarial endometrioma: A retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Analysis of cumulative live birth rate outcomes of three controlled ovarian hyperstimulation protocols in patients with diminished ovarian reserve following laparoscopic cystectomy of ovarial endometrioma: A retrospective cohort study Jiaheng Li, Yijiang Li, Mengnuo Li, Xianling Zhao, Wei Zheng, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3124568/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Aug, 2023 Read the published version in Reproductive Health → Version 1 posted 7 You are reading this latest preprint version Abstract Background: To compare the assisted reproductive outcomes of gonadotropin (Gn)-releasing hormone (GnRH) antagonist, microstimulation, and progestin-primed ovarian stimulation (PPOS) protocols in patients with diminished ovarian reserve (DOR) following laparoscopic cystectomy of ovarial endometrioma. Methods: In this retrospective cohort study, 89 patients with DOR who had undergone in vitro fertilisation/intracytoplasmic sperm injection at the Department of Reproductive Medicine at the Third Affiliated Hospital of Zhengzhou University from 1 January 2018 to 31 December 2020 were included. According to the controlled ovarian hyperstimulation protocols employed, the patients were divided into GnRH antagonist (38 patients), PPOS (27 patients), and microstimulation (24 patients) groups. The basic data and clinical outcomes of the three groups were compared. The main outcome measure was the cumulative live birth rate. Results: No significant differences in the age of the female patients and their spouses and female patients’ body mass index and basal endocrine levels (follicle-stimulating hormone and oestradiol) were noted among the three groups (P > 0.05). The GnRH antagonist group had higher antral follicle counts, greater endometrial thickness on the human chorionic Gn injection day, greater number of oocytes retrieved, and higher two pronuclear embryo counts than did the other two groups. However, the starting dosage of Gn was lower in the GnRH antagonist group than in the other two groups. The microstimulation group had a significantly higher oocyte output rate and high-quality embryo rate than did the other two groups (P < 0.05). No significant differences in the total dosage of Gn, cumulative pregnancy rate, cumulative live birth rate, viable embryo rate, and blastocyst formation rate were observed among the three groups (P > 0.05). Conclusion: For patients aged under 40 years who experienced DOR following laparoscopic cystectomy of ovarial endometrioma, the clinical outcomes of the three controlled ovarian hyperstimulation protocols were similar. However, the cumulative live birth rate was higher in the GnRH antagonist and PPOS groups than in the microstimulation group. diminished ovarian reserve ovarial endometrioma cumulative live birth rate Background Endometriosis is a common oestrogen-dependent gynaecological disease. The incidence of endometriosis in infertile women was reported to be approximately 20–50%( 1 ). Ovarian endometriotic cysts, the most common manifestation of endometriosis, are caused by the recurrent bleeding of the ectopic endometrial tissue in the ovaries during menstruation. This phenomenon results in the formation of ectopic cysts that are filled with accumulated old blood and are also known as chocolate cysts. Laparoscopic cystectomy of ovarial endometrioma is currently the first-line treatment for infertility caused by these cysts( 2 ). This surgical procedure can not only eliminate ectopic lesions but also restore the normal pelvic anatomy, thus alleviating symptoms and improving women’s quality of life. However, this treatment can damage the normal ovarian tissue, resulting in diminished ovarian reserve (DOR)( 3 ). Studies have reported that after laparoscopic cystectomy of ovarial endometrioma, the ovarian response to gonadotropin (Gn) significantly decreased( 4 ), with the incidence of ovarian failure ranging from 2.4–13%( 5 ). Therefore, determining the most appropriate ovulation induction plan for patients experiencing DOR after laparoscopic cystectomy of ovarial endometrioma should be a critical consideration for physicians. This study retrospectively analysed the assisted reproductive outcomes of three ovulation induction regimens to determine a more suitable ovulation induction regimen for patients experiencing DOR following laparoscopic enucleation of ovarian cysts. The findings of this study provide valuable guidance for the clinical treatment of such patients. Materials and methods Patients In this retrospective study, we included patients who had received in vitro fertilisation (IVF) treatment or intracytoplasmic sperm injection (ICSI) at the Department of Reproductive Medicine at the Third Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 and had undergone a single laparoscopic cystectomy of ovarial endometrioma. Because the goal was to compare the effectiveness of different controlled ovarian hyperstimulation protocols, patients were divided into three groups: a Gn-releasing hormone (GnRH) antagonist group, a microstimulation group, and a progestin-primed ovarian stimulation (PPOS) group. Inclusion criteria The inclusion criteria were as follows: 1) age ≤ 40 years; 2) DOR( 6 ), evidenced by the presence of either a) an anti-Mullerian hormone (AMH) level of < 1.1 ng/mL, b) an antral follicle count (AFC) of < 5–7 in both the ovaries, or c) a basal follicle-stimulating hormone (FSH) level of ≥ 10 IU/L in two consecutive menstrual cycles; 3) a history of a single laparoscopic cystectomy of ovarial endometrioma; and 4) first IVF/ICSI-assisted pregnancy cycle. Exclusion criteria The exclusion criteria were as follows: 1) endocrine-related diseases, such as polycystic ovary syndrome and hyperprolactinaemia; 2) any chromosomal abnormality in either spouse; 3) uterine malformations; 4) a history of recurrent miscarriage; 5) diagnosis of adenomyosis through surgery, ultrasound, or magnetic resonance imaging; 6) cycles with incomplete data; and 7) cycles involving the preimplantation genetic diagnosis and preimplantation genetic screening. Controlled ovarian hyperstimulatio protocols 1)GnRH antagonist protocol: Based on the patient’s age, body mass index (BMI), and ovarian reserve, ovulation induction was initiated between the second and fourth day of menstruation by administering Gn. The primary agents used were urinary Gn (Zhuhai Lizhu Group, Lizhu Pharmaceutical Factory) and recombinant FSH (Konafen, Merck, Germany), Procon (MSD, USA), or Lishenbao (Zhuhai Lizhu Group, Lizhu Pharmaceutical Factory). Upon reaching an average follicular diameter of 11 to 12 mm and a serum oestradiol level of > 500 ng/L, the patients were administered GnRH antagonists (Citrek, Merck Serrano, Switzerland) at a dose of 0.25 mg/d. 2)Microstimulation protocol: Between the second and fourth day of menstruation, patients were orally administered 2.5 mg/d of letrozole (Jiangsu Hengrui Pharmaceutical Co., Ltd.) or 50 mg/d of clomiphene citrate (Shanghai Hengshan Pharmaceutical Co., Ltd.). Simultaneously, they were administered an intramuscular injection of human menopausal Gn (urotropin for injection, Zhuhai Lizhu Group, Lizhu Pharmaceutical Factory) at an initial dose of 150 IU/d, which was continued until the human chorionic Gn (hCG) injection day. 3)PPOS: From the second to fourth day of menstruation, patients were orally administered 6–10 mg/d of medroxyprogesterone acetate (Zhejiang Xianju Pharmaceutical Co., Ltd.) and injected 150–225 U/d of Gn until the hCG injection day. The Gn dosage was maintained or adjusted during treatment based on follicle growth and serum hormone levels. When at least one dominant follicle reached a diameter of ≥ 20 mm or three follicles reached a diameter of ≥ 18 mm, hCG (Zhuhai Lizhu Group, Lizhu Pharmaceutical Factory), recombinant hCG (Aize, Merck Serrano, Switzerland), or Dafirin (Iproxen, France) were administered to trigger ovulation. Egg retrieval was performed after 36 h under vaginal ultrasound guidance. Embryo transfer In the GnRH antagonist protocol, given the absence of any contraindications, a fresh cycle transfer was performed first depending on the endometrial thickness and serum hormone levels. Two fresh cleavage-stage embryos or one blastocyst was transferred on day 3 or 5 after oocyte retrieval. If pregnancy was not achieved, frozen–thawed embryo transfer (FET) was performed in subsequent cycles. In the microstimulation and PPOS protocols, vitrification freezing technology was employed for total embryo freezing. Different FET plans were developed based on the specific situation of each patient. Endometrial development or follicle growth and serum hormone levels were continuously monitored, and endometrial preparation was timed accurately. Two frozen–thawed cleavage-stage embryos were transferred 3 days after endometrial preparation or one frozen–thawed blastocyst was transferred 5 days after endometrial preparation. Pregnancy diagnosis Blood hCG levels were measured 14 days after transplantation. Clinical pregnancy was considered if an ultrasound examination performed 30 days after transplantation revealed a gestational sac. Observation indicators The primary outcome was the cumulative live birth rate. In an IVF/ICSI cycle (which includes one oocyte retrieval cycle, fresh embryo transfer, and subsequent FETs), the number of cycles resulting in the first live birth (defined as ≥ 28 weeks of gestation) was used as the numerator and the number of oocyte retrieval cycles was used as the denominator. The observation was continued until one live birth was observed or all embryos were utilised( 7 , 8 ). The secondary outcomes were patient general characteristics, the number of oocytes retrieved, the oocyte output rate, the number of two pronuclear (2PN) embryos, the viable embryo rate, the high-quality embryo rate, the blastocyst formation rate, and the cumulative pregnancy rate. Statistical analysis All statistical analyses were performed using SPSS(Statistical Package for the Social Sciences)version 26.0. Normally distributed quantitative data are presented as the mean ± standard deviation and were compared between groups using an analysis of variance. Quantitative data that were not normally distributed are expressed as the median (interquartile interval) and were compared between groups using a nonparametric rank sum test. Qualitative data are presented as the percentage and were compared between groups using a chi-square test or a corrected chi-square test. For the primary outcome measures, binary meta-logistic regression was performed after adjustment for confounding factors. A P value of < 0.05 was considered statistically significant. Results Eighty-nine patients who had undergone their first postoperative IVF/ICSI-assisted pregnancy cycle were included in this retrospective analysis. Of the 89 patients, 38, 27, and 24 were included in the PPOS, GnRH antagonist, and microstimulation groups, respectively. No significant differences were noted in the age of the female patients and their spouses and in the BMI and basal endocrine levels (FSH and oestradiol) of the female patients among the three groups (P > 0.05). The GnRH antagonist group had a significantly higher AFC than did the other two groups (P < 0.05; Table 1 ). Table 1 The general data of patients in four groups Item progestin-primed ovarian stimulation group GnRH-antagonist group Microstimulati-on group Z/x2 value P value No. of cases 38 27 24 Female age(year) 33.34 ± 4.14 32.30 ± 3.83 34.13 ± 4.50 1.331 0.270 Male age(year) 35.21 ± 7.88 33.11 ± 3.11 34.67 ± 4.92 0.990 0.376 Female body mass index(kg/m2) 22.93 ± 2.81 23.76 ± 3.11 23.81 ± 2.92 0.920 0.402 Duration of infertility(year) 4.01 ± 3.58 4.41 ± 3.15 2.99 ± 2.87 1.226 0.299 Antral follicle count 6.16 ± 2.46 11.30 ± 6.72 bc 6.50 ± 3.43 12.008 P<0.001 Basal follicle stimulating hormone(IU/L) 9.69 ± 5.02 8.20 ± 3.02 10.23 ± 4.35 1.565 0.215 Basal luteillizing homon(IU/L) 12.91 ± 42.90 4.73 ± 2.09 4.55 ± 2.28 0.936 0.396 Main etiology of infertility(%) Tubal factor 52.6(20/38) 44.4(12/27) 70.8(17/24) 4.623 0.099 Diminished ovarian reserve 73.7(28/38) 66.7(18/27) 54.1(13/24) 1.913 0.384 Male factor 26.3(10/38) 22.2(6/27) 16.1(4/24) 0.655 0.721 Other factors 57.8(22/38) 62.9(17/27) 70.8(17/24) 1.596 0.450 Starting dosage of Gn 286.32 ± 72.12 a 230.56 ± 65.63 265.63 ± 49.35 4.088 0.020 Dosage of Gn used 2806.58 ± 747.25 2467.11 ± 755.83 2818.75 ± 742.44 2.013 0.140 Endometrial thickness on HCG injection day 8.03 ± 1.74 10.50 ± 2.29 bc 6.93 ± 1.83 23.053 P<0.001 a: Comparison with GnRH-antagonist group; b: Comparison with microstimulation group; c: Comparison with PPOS group The starting dosage of Gn significantly differed among the three groups (P < 0.05). The GnRH antagonist group was administered a significantly lower starting dosage of Gn than the PPOS group. However, the total dosage of Gn did not significantly differ among the three groups. The endometrial thickness on the hCG injection day in the GnRH antagonist group was significantly higher than that in the other two groups (Table 1 ). The cumulative pregnancy rate, cumulative live birth rate, viable embryo rate, and blastocyst formation rate did not significantly differ among the three groups (P > 0.05). The numbers of oocytes retrieved and 2PN embryos in the GnRH antagonist group were superior to those in the other two groups. However, the oocyte output rate was significantly higher in the microstimulation group than in the other two groups. The rate of high-quality embryos significantly differed among the three groups, with the PPOS group exhibiting the highest rate, followed by the GnRH antagonist and microstimulation groups (54.9% [67/122] vs 46.6% [62/133] vs 29.7% [19/64], x2 = 10.749, P < 0.005; Table 2 ). Table 2 Comparison of clinical outcomes of patients among three protocols Item progestin-primed ovarian stimulation group GnRH-antagonist group microstimulation group Z/x2 value P value No. of oocytes retrieved 4.31 ± 2.01 7.42 ± 5.17 bc 3.88 ± 2.31 8.512 P<0.001 Oocytes output rate(%) 63.2(96/152) 57.9(136/235) 91.2(52/57) ac 22.208 P<0.001 No.2PN 3.39 ± 1.69 5.11 ± 4.09 bc 2.67 ± 2.06 5.595 0.005 Available embryo rate(%) 83.6(102/122) 90.2(120/133) 90.9(50/64) 3.216 0.200 High-quality embryo rate(%) 54.9(67/122) 46.6(62/133) bc 29.7(19/64) c 10.749 0.005 Blastocyst formation rate(%) 65.2(30/46) 57.8(48/83) 50.0(11/22) 1.518 0.468 Clinical pregnancy rate (%) 44.7(17/38) 55.6(15/27) 29.2(7/24) 3.617 0.164 Cumulative live birth rate(%) 34.2(13/38) 48.1(13/27) 20.8(4/24) 4.188 0.123 a: Comparison with GnRH-antagonist group; b: Comparison with microstimulation group; c: Comparison with PPOS group Binary logistic regression analysis of the cumulative live birth rate was performed using the cumulative live birth rate as the observation index. This analysis controlled for confounding factors, namely the female patient’s age (continuous variable), the female patient’s BMI (continuous variable), infertility type (primary/secondary), AFC (continuous variable), and ovulation stimulation protocol (GnRH antagonist, PPOS, and microstimulation protocols). The cumulative live birth rate in the microstimulation group was lower than that in the GnRH antagonist group (adjusted odds ratio [aOR] = 0.153, 95% confidence interval [CI] = 0.036–0.654, P = 0.011). However, the cumulative live birth rate did not significantly differ between the PPOS and GnRH antagonist groups (aOR = 0.332, 95% CI = 0.093–1.18, P = 0.088; Table 3 ). Table 3 Binary logistic regression analysis of factors affecting cumulative live birth rate Factors Wald aOR 95%CI P值 Maternal age 0.250 1.037 0.891–1.198 0.617 Female body mass index 1.176 0.908 0.763–1.081 0.278 Type of infertility(primary/ secondary) 0.166 1.265 0.409–3.908 0.683 Antral follicle count 0.573 0.958 0.858–1.070 0.449 COH protocols GnRH-antagonist group 1 progestin-primed ovarian stimulation group 2.906 0.332 0.093–1.180 0.088 microstimulation group 6.428 0.153 0.036–0.654 0.011 Discussion Endometriosis is a common gynaecological condition in women of childbearing age. This condition can distort the anatomical structures of the fallopian tubes and ovaries( 9 ), leading to inflammation( 10 , 11 ), oxidative damage( 12 ), and harm to oocytes( 13 ), and harm to oocytes( 14 ). Currently, laparoscopic enucleation is the preferred treatment modality for ovarian cysts measuring ≥ 3 cm in diameter( 3 ). However, studies have indicated that women who undergo this surgery may respond poorly to Gn stimulation, produce fewer oocytes, and experience DOR, resulting in higher cycle cancellation rates of IVF and embryo transfer cycles as well as lower embryo implantation and clinical pregnancy rates( 15 ). Controlled ovulation induction is a crucial step in assisted reproductive technology (ART), and a personalised approach can substantially improve the clinical outcomes of ART. A previous study reported that growth hormone or percutaneous androgen supplementation during ovulation induction therapy significantly improved the cumulative pregnancy rate and live birth rate in patients with a poor ovarian response( 16 ). Currently, ovulation induction protocols commonly used in clinical practice for patients with DOR include GnRH antagonist, microstimulation, and PPOS protocols. For patients experiencing DOR following laparoscopic cystectomy of ovarial endometrioma, determining how to obtain high-quality oocytes and embryos through appropriate ovulation induction protocols to reduce stress among patients is an urgent problem in clinical practice. Most studies have indicated that patients with endometriosis should undergo an ultra-long treatment regimen, mainly due to the inhibitory effect of the GnRH agonist on the ectopic endometrial tissue( 17 ). However, a review published in 2021 suggested that the GnRH antagonist or PPOS protocol may be more suitable than ultra-long treatment regimens for patients with endometriosis( 18 ). GnRH antagonists can competitively bind to pituitary GnRH receptors, reducing the secretion of pituitary Gn. Because of their direct antagonist action( 19 ), GnRH antagonists maintain pituitary responsiveness and can thus maximise the ovarian response to Gn. A retrospective study conducted in China in 2019( 20 ) compared the assisted reproductive outcomes of patients with endometriosis using GnRH antagonists, long agonist protocol and prolonged agonist protocol. The results revealed no significant differences in hCG positivity, clinical pregnancy, and total embryo implantation rates among the three groups. However, among patients with DOR, the GnRH antagonist group had a higher viable embryo rate than did the rectangular regimen group, and both the total numbers of Gn administration and medication days were lower in the GnRH antagonist group than in the other two groups. The use of GnRH antagonists in patients with endometriosis and infertility resulted in similar pregnancy outcomes as the rectangular and ultra-long regimens. However, GnRH antagonists reduced treatment costs and time and resulted in a higher viable embryo rate. A meta-analysis( 21 ) published in 2022 included 13,050 cycles, with 5,984 patients using a GnRH antagonist and 7,066 patients not using an antagonist. The results demonstrated that the use of a GnRH antagonist was associated with higher live birth rates. Moreover, a significant improvement in live birth rates was noted in women with an AMH level of < 1 ng/mL and women aged ≥ 35 years. The findings indicate that the use of GnRH antagonists significantly reduces the cycle cancellation rate and increases the number of frozen embryos, possibly due to improvements in embryo quality and endometrial receptivity. This finding is consistent with the results of the present study, which demonstrated that the GnRH antagonist group had a higher rate of high-quality embryos than did the microstimulation group. In 2015, Yanping Kuang( 22 ) first proposed the PPOS protocol, which involves adding exogenous progesterone during the follicular phase. A meta-analysis published in 2021( 23 ) reported that in the DOR population, the PPOS protocol resulted in a lower incidence of early-onset luteinising hormone (LH) peaks and ovarian hyperstimulation syndrome than did the GnRH antagonist regimen, GnRH agonist regimen, and natural cycle. The results of this study revealed no significant difference in the cumulative pregnancy rate among the three groups. However, the cumulative live birth rate was higher in the GnRH antagonist and PPOS groups than in the microstimulation group. This finding is similar to that of a retrospective study( 24 ) conducted in China in 2020, which included 285 patients according to the Poseidon standard. The results showed that the cumulative clinical pregnancy rate was higher in the GnRH antagonist group than in the microstimulation and PPOS groups. Moreover, in the present study, the numbers of retrieved eggs and 2PN embryos in the GnRH antagonist group were higher than those in the other two groups. This finding may be associated with the larger dosage and longer duration of Gn treatment in the GnRH antagonist protocol, which provides more opportunities for follicular recruitment and growth. Thus, for patients with DOR following laparoscopic cystectomy of ovarial endometrioma, the GnRH antagonist protocol is a more suitable ovulation induction regimen than the microstimulation protocol. In 2019, a domestic meta-analysis( 25 ) included 2,270 cycles in the PPOS group and 2,463 cycles in the microstimulation group. The results revealed that for patients with DOR, the PPOS protocol resulted in a higher rate of high-quality embryos and a lower rate of cycle cancellation than did the microstimulation protocol. This finding is consistent with the results of the present study. The microstimulation protocol, which does not involve downregulation, is prone to premature LH peaks and follicular ovulation, resulting in a higher rate of cycle cancellation. However, the results of this study indicate that compared with the microstimulation protocol, the PPOS protocol led to a higher cumulative activity rate. Therefore, the PPOS protocol resulted in better clinical outcomes in the patients included in the current study. The results of this study are inconsistent with those of a retrospective study( 26 ) published in 2018, which included 186 POR patient cycles from 2014 to 2016. The results showed that the PPOS protocol resulted in a higher clinical pregnancy rate and live birth rate than did the GnRH antagonist protocol. The inconsistency in findings may be attributable to differences in the included population and sample size between the previous and current study. Few studies have evaluated the effectiveness of ovulation induction protocols after laparoscopic cystectomy of ovarial endometrioma. This study included patients experiencing DOR after laparoscopic cystectomy of ovarial endometrioma and investigated the effectiveness of PPOS, microstimulation, and GnRH antagonist protocols by determining the cumulative live birth rate. A limitation of this study is the small sample size, which may have led to the lack of significant differences between the main observation indicators of this study. As of the data collection period, there were still many embryos that were frozen and had not been transferred or had not yet resulted in a live birth following successful pregnancy. Furthermore, some patients were still pregnant. Further follow-up is essential to obtain more informative results. In addition, ovarian cysts are highly complex in nature. More research is needed to determine the optimal ovulation induction plan for patients following ovarian cyst surgery. Conclusion For patients aged under 40 years who experienced DOR after laparoscopic cystectomy of ovarial endometrioma, the clinical outcomes of the three ovarian induction protocols were similar. However, the cumulative live birth rate was higher in the GnRH antagonist and PPOS groups than in the microstimulation group. Abbreviations Gn gonadotropin GnRH gonadotropin releasing hormone PPOS progestin-primed ovarian stimulation DOR diminished ovarian reserve IVF in vitro fertilization ICSI intracytoplasmic sperm injection AMH anti-Mullerian hormone AFC antral follicle count FSH follicle-stimulating hormone BMI body mass index hCG human chorionic gonadotropin FET frozen–thawed embryo transfer 2PN two pronuclear LH luteinising hormone Declarations Acknowledgments The authors are grateful to physicians and coordinators who enrolled patients and collected data from all women who participated in this study. Author’ contributions YJL,JL, JHL,YCG contributed to the conception and design of the study. MNL,XLZ,WZ was involved in the acquisition of data collection .YJL, JWZ,YCZ analyzed data and drafted the manuscript. All authors revised the article and gave their final approval of the submitted version. Funding This research was funded by National Key R&D Program "Fertility Health and Health Security for Women and Children": Clinical Cohort and Intervention Study on Genetic Problems in Assisted Reproduction Offspring (No:2021YFC2700602), the Medical Science and Technology Research Project of Henan Province (Joint Construction) (No:LHGJ20190365). Availability of data and materials The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The study was approved by the ethics committee of the Third Affiliated Hospital of Zhengzhou University and performed in accordance with the principles of the Declaration of Helsinki. Consent for publication Not applicable. Conflict of interest The authors have nothing to disclose. References Professional Committee on Reproductive Medicine CMDA. Guideline for the diagnosis and treatment of endometriosis (Third edition). Chinese Journal of Obstetrics and Gynecology. 2021;56(12):812-24. Recommendations for the Surgical Treatment of Endometriosis. Part 1: Ovarian Endometrioma. Human Reproduction Open. 2017. Dunselman G, Vermeulen N, Becker C, Calhaz-Jorge C, Nelen W. ESHRE guideline: Management of women with endometriosis. Human Reproduction. 2014;29(3). Ruiz-Flores FJ, Garcia-Velasco JA. Is there a benefit for surgery in endometrioma-associated infertility? Current Opinion in Obstetrics & Gynecology. 2012;24(3):136-40. Benaglia L, Somigliana E, Vighi V, Ragni G, Vercellini P, Fedele L. Rate of severe ovarian damage following surgery for endometriomas. Human Reproduction. 2010;25(3):678-82. Reserve； EGoCoCDMoDO, Association REFPSoCSoFPuCPM. Consensus on clinical diagnosis and management of diminished ovarian reserve. Journal of Reproductive Medicine. 2022;31(4):10. C NPP, A B, Panagiotis Drakopoulos BDE, F JP, Antonio Pellicer G, Samuel Santos-Ribeiro BDH, Herman Tournaye BD, et al. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for invitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including 15,000 women. Fertility and Sterility. 2018;110(4):661-70. Professional Committee on Reproductive Medicine CMDA. Cumulative delivery/live birth rate of complete ovarian stimulation cycle consensus. Chinese Journal of Reproduction and Contraception. 2018;38(12):6. Young, Vicky, J., Brown, Jeremy, K., et al. The role of the peritoneum in the pathogenesis of endometriosis. Human Reproduction Update. 2013. Gazvani R, Templeton A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction. 2002;123(2):217. Harada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertility and Sterility. 2001;76(1):1-10. A SM, B BS. Oxidative stress status in normal ovarian cortex surrounding ovarian endometriosis. Fertility and Sterility. 2010;93(7):2431-2. Gupta S. Impact of ovarian endometrioma on assisted reproduction outcomes. Reproductive Biomedicine Online. 2006;13. Busacca M, Vignali M. Ovarian endometriosis: from pathogenesis to surgical treatment. Current Opinion in Obstetrics & Gynecology. 2003;15(4):321. Urman B, Alper E, Yakin K, Oktem O, Aksoy S, Alatas C, et al. Removal of unilateral endometriomas is associated with immediate and sustained reduction in ovarian reserve. Reproductive Biomedicine Online. 2013;27(2):212-6. Jeve YB, Bhandari HM. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis. J Hum Reprod Sci. 2016;9(2):70-81. Live birth rate comparison of three controlled ovarian stimulation protocols for in vitro fertilization-embryo transfer in patients with diminished ovarian reserve after endometrioma cystectomy: a retrospective study. Journal of Ovarian Research. 2020;13(1):1-8. Ata B, Telek SB. Assisted reproductive technology for women with endometriosis, a clinically oriented review. Curr Opin Obstet Gynecol. 2021;33(3):225-31. C. B, Lambalk, F. R, Banga, J. A, Huirne, et al. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Human Reproduction Update. 2017. Ya Y, Kai W, Qiuping Y, Shen T, Kun L, Liming Z, et al. Controlled ovarian stimulation protocols in endometriosis patients: with antagonist or agonist? Journal of Zhejiang University (Medical Sciences). 2019;48(2):165-73. Hurley EG, Sun F, Zhang H, Polotsky AJ, Rios JS. MINIMAL STIMULATION USING GONADOTROPIN-RELEASING HORMONE ANTAGONIST IS ASSOCIATED WITH HIGHER LIVE BIRTH RATES: A NATIONAL STUDY OF 13,050 CYCLES. Fertility and Sterility. 2020;114(3):e286-. Yanping, Kuang, Qiuju, Chen, Yonglun, Fu, et al. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertility & Sterility. 2015. Guan S, Feng Y, Huang Y, Huang J. Progestin-Primed Ovarian Stimulation Protocol for Patients in Assisted Reproductive Technology: A Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2021;12:702558. Juan Z, Liming Z, Yiting S, Aili X, Mai L, Kun L. Comparison of the clinical outcomes of three ovulation induction protocols in elderly patients with decline in ovarian reserve. Chinese Journal of Reproduction and Contraception. 2020;40(3):194-200. Xin-yue H, Yi-hua Y, Yu F, Ai-ping QN. Application effect of progestin-primed ovarian stimulation and micro-stimulation protocol for patients with poor ovarian response in IVF-ET treatment:a Meta analysis. Journal of Reproductive Medicine. 2019;28(10):1212-8. Huang P, Tang M, Qin A. Progestin-primed ovarian stimulation is a feasible method for poor ovarian responders undergoing in IVF/ICSI compared to a GnRH antagonist protocol: A retrospective study. Journal of Gynecology Obstetrics & Human Reproduction. 2018. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Aug, 2023 Read the published version in Reproductive Health → Version 1 posted Editorial decision: Major revision 25 Jul, 2023 Reviews received at journal 21 Jul, 2023 Reviewers agreed at journal 14 Jul, 2023 Reviewers invited by journal 14 Jul, 2023 Submission checks completed at journal 30 Jun, 2023 Editor assigned by journal 30 Jun, 2023 First submitted to journal 29 Jun, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3124568","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":214537708,"identity":"5db39056-4a74-45c2-8c72-301b774b727d","order_by":0,"name":"Jiaheng Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYBACPoYzbAwfKv7JsbG3HyBOCxtQC+OMMweM+XjOJBCrhYeNmbftQOI8CQcDIrUwnj32gIftTnqbBEMCw4+KbcTYci7dQILnWW6bdOMBxp4zt4nRcsZMwkCCObdN5kACM2MbsVoSDJjT2UAk8VoOJBxOIE2LZMOBNMM2YCAfJMov/BJnzKT//rORl29vP/jgRwURWhgkDiDYB3ApQrOmgTh1o2AUjIJRMIIBAHf3OzWF70GvAAAAAElFTkSuQmCC","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":true,"prefix":"","firstName":"Jiaheng","middleName":"","lastName":"Li","suffix":""},{"id":214537712,"identity":"8d2eec54-bb08-4cec-a36b-88c53402cddc","order_by":1,"name":"Yijiang Li","email":"","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":false,"prefix":"","firstName":"Yijiang","middleName":"","lastName":"Li","suffix":""},{"id":214537717,"identity":"1a3fb30f-90ef-4bdc-ae87-c1349c174e52","order_by":2,"name":"Mengnuo Li","email":"","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":false,"prefix":"","firstName":"Mengnuo","middleName":"","lastName":"Li","suffix":""},{"id":214537718,"identity":"b5ef9816-e02e-46da-a143-3eb1b6723df4","order_by":3,"name":"Xianling Zhao","email":"","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":false,"prefix":"","firstName":"Xianling","middleName":"","lastName":"Zhao","suffix":""},{"id":214537722,"identity":"f3e7492d-0a70-48d3-865c-402778311ead","order_by":4,"name":"Wei Zheng","email":"","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Zheng","suffix":""},{"id":214537723,"identity":"a5d314e8-a004-43dd-b9f0-8612ab0dae4e","order_by":5,"name":"Junwei Zhang","email":"","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":false,"prefix":"","firstName":"Junwei","middleName":"","lastName":"Zhang","suffix":""},{"id":214537725,"identity":"0186b649-ee14-4280-815b-e8e7c68b79e2","order_by":6,"name":"Yuchao Zhang","email":"","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":false,"prefix":"","firstName":"Yuchao","middleName":"","lastName":"Zhang","suffix":""},{"id":214537727,"identity":"828606ad-9d09-4dc3-a708-c8a2ded0b3bf","order_by":7,"name":"Jing Li","email":"","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Li","suffix":""},{"id":214537728,"identity":"b3f345c4-76c4-42af-8e8b-d67d8c70c98c","order_by":8,"name":"Yichun Guan","email":"","orcid":"","institution":"The Third Affiliated Hospital of ZhengZhou University","correspondingAuthor":false,"prefix":"","firstName":"Yichun","middleName":"","lastName":"Guan","suffix":""}],"badges":[],"createdAt":"2023-06-29 11:59:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3124568/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3124568/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12978-023-01671-3","type":"published","date":"2023-08-29T15:08:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":42781873,"identity":"aeb10df7-d3e1-4002-8d3b-a17bf509ebac","added_by":"auto","created_at":"2023-09-07 15:13:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":323202,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3124568/v1/ce8010d5-32e5-4e43-9ef7-585311d05cce.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of cumulative live birth rate outcomes of three controlled ovarian hyperstimulation protocols in patients with diminished ovarian reserve following laparoscopic cystectomy of ovarial endometrioma: A retrospective cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eEndometriosis is a common oestrogen-dependent gynaecological disease. The incidence of endometriosis in infertile women was reported to be approximately 20\u0026ndash;50%(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Ovarian endometriotic cysts, the most common manifestation of endometriosis, are caused by the recurrent bleeding of the ectopic endometrial tissue in the ovaries during menstruation. This phenomenon results in the formation of ectopic cysts that are filled with accumulated old blood and are also known as chocolate cysts. Laparoscopic cystectomy of ovarial endometrioma is currently the first-line treatment for infertility caused by these cysts(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This surgical procedure can not only eliminate ectopic lesions but also restore the normal pelvic anatomy, thus alleviating symptoms and improving women\u0026rsquo;s quality of life. However, this treatment can damage the normal ovarian tissue, resulting in diminished ovarian reserve (DOR)(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Studies have reported that after laparoscopic cystectomy of ovarial endometrioma, the ovarian response to gonadotropin (Gn) significantly decreased(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), with the incidence of ovarian failure ranging from 2.4\u0026ndash;13%(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Therefore, determining the most appropriate ovulation induction plan for patients experiencing DOR after laparoscopic cystectomy of ovarial endometrioma should be a critical consideration for physicians. This study retrospectively analysed the assisted reproductive outcomes of three ovulation induction regimens to determine a more suitable ovulation induction regimen for patients experiencing DOR following laparoscopic enucleation of ovarian cysts. The findings of this study provide valuable guidance for the clinical treatment of such patients.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003ePatients\u003c/p\u003e \u003cp\u003eIn this retrospective study, we included patients who had received in vitro fertilisation (IVF) treatment or intracytoplasmic sperm injection (ICSI) at the Department of Reproductive Medicine at the Third Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 and had undergone a single laparoscopic cystectomy of ovarial endometrioma. Because the goal was to compare the effectiveness of different controlled ovarian hyperstimulation protocols, patients were divided into three groups: a Gn-releasing hormone (GnRH) antagonist group, a microstimulation group, and a progestin-primed ovarian stimulation (PPOS) group.\u003c/p\u003e \u003cp\u003eInclusion criteria\u003c/p\u003e \u003cp\u003eThe inclusion criteria were as follows: 1) age\u0026thinsp;\u0026le;\u0026thinsp;40 years; 2) DOR(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), evidenced by the presence of either a) an anti-Mullerian hormone (AMH) level of \u0026lt;\u0026thinsp;1.1 ng/mL, b) an antral follicle count (AFC) of \u0026lt;\u0026thinsp;5\u0026ndash;7 in both the ovaries, or c) a basal follicle-stimulating hormone (FSH) level of \u0026ge;\u0026thinsp;10 IU/L in two consecutive menstrual cycles; 3) a history of a single laparoscopic cystectomy of ovarial endometrioma; and 4) first IVF/ICSI-assisted pregnancy cycle.\u003c/p\u003e \u003cp\u003eExclusion criteria\u003c/p\u003e \u003cp\u003eThe exclusion criteria were as follows: 1) endocrine-related diseases, such as polycystic ovary syndrome and hyperprolactinaemia; 2) any chromosomal abnormality in either spouse; 3) uterine malformations; 4) a history of recurrent miscarriage; 5) diagnosis of adenomyosis through surgery, ultrasound, or magnetic resonance imaging; 6) cycles with incomplete data; and 7) cycles involving the preimplantation genetic diagnosis and preimplantation genetic screening.\u003c/p\u003e \u003cp\u003eControlled ovarian hyperstimulatio protocols\u003c/p\u003e \u003cp\u003e1)GnRH antagonist protocol: Based on the patient\u0026rsquo;s age, body mass index (BMI), and ovarian reserve, ovulation induction was initiated between the second and fourth day of menstruation by administering Gn. The primary agents used were urinary Gn (Zhuhai Lizhu Group, Lizhu Pharmaceutical Factory) and recombinant FSH (Konafen, Merck, Germany), Procon (MSD, USA), or Lishenbao (Zhuhai Lizhu Group, Lizhu Pharmaceutical Factory). Upon reaching an average follicular diameter of 11 to 12 mm and a serum oestradiol level of \u0026gt;\u0026thinsp;500 ng/L, the patients were administered GnRH antagonists (Citrek, Merck Serrano, Switzerland) at a dose of 0.25 mg/d.\u003c/p\u003e \u003cp\u003e2)Microstimulation protocol: Between the second and fourth day of menstruation, patients were orally administered 2.5 mg/d of letrozole (Jiangsu Hengrui Pharmaceutical Co., Ltd.) or 50 mg/d of clomiphene citrate (Shanghai Hengshan Pharmaceutical Co., Ltd.). Simultaneously, they were administered an intramuscular injection of human menopausal Gn (urotropin for injection, Zhuhai Lizhu Group, Lizhu Pharmaceutical Factory) at an initial dose of 150 IU/d, which was continued until the human chorionic Gn (hCG) injection day.\u003c/p\u003e \u003cp\u003e3)PPOS: From the second to fourth day of menstruation, patients were orally administered 6\u0026ndash;10 mg/d of medroxyprogesterone acetate (Zhejiang Xianju Pharmaceutical Co., Ltd.) and injected 150\u0026ndash;225 U/d of Gn until the hCG injection day.\u003c/p\u003e \u003cp\u003eThe Gn dosage was maintained or adjusted during treatment based on follicle growth and serum hormone levels. When at least one dominant follicle reached a diameter of \u0026ge;\u0026thinsp;20 mm or three follicles reached a diameter of \u0026ge;\u0026thinsp;18 mm, hCG (Zhuhai Lizhu Group, Lizhu Pharmaceutical Factory), recombinant hCG (Aize, Merck Serrano, Switzerland), or Dafirin (Iproxen, France) were administered to trigger ovulation. Egg retrieval was performed after 36 h under vaginal ultrasound guidance.\u003c/p\u003e \u003cp\u003eEmbryo transfer\u003c/p\u003e \u003cp\u003eIn the GnRH antagonist protocol, given the absence of any contraindications, a fresh cycle transfer was performed first depending on the endometrial thickness and serum hormone levels. Two fresh cleavage-stage embryos or one blastocyst was transferred on day 3 or 5 after oocyte retrieval. If pregnancy was not achieved, frozen\u0026ndash;thawed embryo transfer (FET) was performed in subsequent cycles. In the microstimulation and PPOS protocols, vitrification freezing technology was employed for total embryo freezing. Different FET plans were developed based on the specific situation of each patient. Endometrial development or follicle growth and serum hormone levels were continuously monitored, and endometrial preparation was timed accurately. Two frozen\u0026ndash;thawed cleavage-stage embryos were transferred 3 days after endometrial preparation or one frozen\u0026ndash;thawed blastocyst was transferred 5 days after endometrial preparation.\u003c/p\u003e \u003cp\u003ePregnancy diagnosis\u003c/p\u003e \u003cp\u003eBlood hCG levels were measured 14 days after transplantation. Clinical pregnancy was considered if an ultrasound examination performed 30 days after transplantation revealed a gestational sac.\u003c/p\u003e \u003cp\u003eObservation indicators\u003c/p\u003e \u003cp\u003eThe primary outcome was the cumulative live birth rate. In an IVF/ICSI cycle (which includes one oocyte retrieval cycle, fresh embryo transfer, and subsequent FETs), the number of cycles resulting in the first live birth (defined as \u0026ge;\u0026thinsp;28 weeks of gestation) was used as the numerator and the number of oocyte retrieval cycles was used as the denominator. The observation was continued until one live birth was observed or all embryos were utilised(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe secondary outcomes were patient general characteristics, the number of oocytes retrieved, the oocyte output rate, the number of two pronuclear (2PN) embryos, the viable embryo rate, the high-quality embryo rate, the blastocyst formation rate, and the cumulative pregnancy rate.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using SPSS(Statistical Package for the Social Sciences)version 26.0. Normally distributed quantitative data are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and were compared between groups using an analysis of variance. Quantitative data that were not normally distributed are expressed as the median (interquartile interval) and were compared between groups using a nonparametric rank sum test. Qualitative data are presented as the percentage and were compared between groups using a chi-square test or a corrected chi-square test. For the primary outcome measures, binary meta-logistic regression was performed after adjustment for confounding factors. A P value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eEighty-nine patients who had undergone their first postoperative IVF/ICSI-assisted pregnancy cycle were included in this retrospective analysis. Of the 89 patients, 38, 27, and 24 were included in the PPOS, GnRH antagonist, and microstimulation groups, respectively. No significant differences were noted in the age of the female patients and their spouses and in the BMI and basal endocrine levels (FSH and oestradiol) of the female patients among the three groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The GnRH antagonist group had a significantly higher AFC than did the other two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe general data of patients in four groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eItem\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eprogestin-primed ovarian stimulation group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGnRH-antagonist group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMicrostimulati-on group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eZ/x2 value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale age(year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.34\u0026thinsp;\u0026plusmn;\u0026thinsp;4.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.30\u0026thinsp;\u0026plusmn;\u0026thinsp;3.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.13\u0026thinsp;\u0026plusmn;\u0026thinsp;4.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.331\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.270\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale age(year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.21\u0026thinsp;\u0026plusmn;\u0026thinsp;7.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.11\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.67\u0026thinsp;\u0026plusmn;\u0026thinsp;4.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale body mass index(kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.93\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.76\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.81\u0026thinsp;\u0026plusmn;\u0026thinsp;2.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.920\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.402\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of infertility(year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.01\u0026thinsp;\u0026plusmn;\u0026thinsp;3.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.41\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.99\u0026thinsp;\u0026plusmn;\u0026thinsp;2.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntral follicle count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.30\u0026thinsp;\u0026plusmn;\u0026thinsp;6.72\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u003c0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasal follicle stimulating hormone(IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.69\u0026thinsp;\u0026plusmn;\u0026thinsp;5.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.20\u0026thinsp;\u0026plusmn;\u0026thinsp;3.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.23\u0026thinsp;\u0026plusmn;\u0026thinsp;4.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.565\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasal luteillizing homon(IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.91\u0026thinsp;\u0026plusmn;\u0026thinsp;42.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.73\u0026thinsp;\u0026plusmn;\u0026thinsp;2.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.936\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.396\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eMain etiology of infertility(%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTubal factor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.6(20/38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.4(12/27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70.8(17/24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.623\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiminished ovarian\u003c/p\u003e \u003cp\u003ereserve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.7(28/38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.7(18/27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54.1(13/24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.913\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale factor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.3(10/38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.2(6/27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.1(4/24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.721\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther factors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.8(22/38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.9(17/27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70.8(17/24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.450\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStarting dosage of Gn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e286.32\u0026thinsp;\u0026plusmn;\u0026thinsp;72.12\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e230.56\u0026thinsp;\u0026plusmn;\u0026thinsp;65.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e265.63\u0026thinsp;\u0026plusmn;\u0026thinsp;49.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.088\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDosage of Gn used\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2806.58\u0026thinsp;\u0026plusmn;\u0026thinsp;747.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2467.11\u0026thinsp;\u0026plusmn;\u0026thinsp;755.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2818.75\u0026thinsp;\u0026plusmn;\u0026thinsp;742.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometrial thickness on HCG injection day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.03\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.50\u0026thinsp;\u0026plusmn;\u0026thinsp;2.29\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.93\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u003c0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003ea: Comparison with GnRH-antagonist group;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eb: Comparison with microstimulation group;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003ec: Comparison with PPOS group\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe starting dosage of Gn significantly differed among the three groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The GnRH antagonist group was administered a significantly lower starting dosage of Gn than the PPOS group. However, the total dosage of Gn did not significantly differ among the three groups. The endometrial thickness on the hCG injection day in the GnRH antagonist group was significantly higher than that in the other two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe cumulative pregnancy rate, cumulative live birth rate, viable embryo rate, and blastocyst formation rate did not significantly differ among the three groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The numbers of oocytes retrieved and 2PN embryos in the GnRH antagonist group were superior to those in the other two groups. However, the oocyte output rate was significantly higher in the microstimulation group than in the other two groups. The rate of high-quality embryos significantly differed among the three groups, with the PPOS group exhibiting the highest rate, followed by the GnRH antagonist and microstimulation groups (54.9% [67/122] vs 46.6% [62/133] vs 29.7% [19/64], x2\u0026thinsp;=\u0026thinsp;10.749, P\u0026thinsp;\u0026lt;\u0026thinsp;0.005; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical outcomes of patients among three protocols\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eItem\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eprogestin-primed ovarian stimulation group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGnRH-antagonist group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003emicrostimulation group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eZ/x2 value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of oocytes retrieved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.42\u0026thinsp;\u0026plusmn;\u0026thinsp;5.17\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.512\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u003c0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOocytes output rate(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.2(96/152)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.9(136/235)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91.2(52/57)\u003csup\u003eac\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22.208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u003c0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.2PN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.11\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.595\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAvailable embryo rate(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83.6(102/122)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90.2(120/133)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90.9(50/64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-quality embryo rate(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.9(67/122)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.6(62/133)\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.7(19/64)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.749\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlastocyst formation rate(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.2(30/46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.8(48/83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.0(11/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.518\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.468\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical pregnancy rate\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.7(17/38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.6(15/27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.2(7/24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.164\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCumulative live birth rate(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.2(13/38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.1(13/27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.8(4/24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003ea: Comparison with GnRH-antagonist group;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eb: Comparison with microstimulation group;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003ec: Comparison with PPOS group\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBinary logistic regression analysis of the cumulative live birth rate was performed using the cumulative live birth rate as the observation index. This analysis controlled for confounding factors, namely the female patient\u0026rsquo;s age (continuous variable), the female patient\u0026rsquo;s BMI (continuous variable), infertility type (primary/secondary), AFC (continuous variable), and ovulation stimulation protocol (GnRH antagonist, PPOS, and microstimulation protocols). The cumulative live birth rate in the microstimulation group was lower than that in the GnRH antagonist group (adjusted odds ratio [aOR]\u0026thinsp;=\u0026thinsp;0.153, 95% confidence interval [CI]\u0026thinsp;=\u0026thinsp;0.036\u0026ndash;0.654, P\u0026thinsp;=\u0026thinsp;0.011). However, the cumulative live birth rate did not significantly differ between the PPOS and GnRH antagonist groups (aOR\u0026thinsp;=\u0026thinsp;0.332, 95% CI\u0026thinsp;=\u0026thinsp;0.093\u0026ndash;1.18, P\u0026thinsp;=\u0026thinsp;0.088; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBinary logistic regression analysis of factors affecting cumulative live birth rate\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWald\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eaOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP值\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.891\u0026ndash;1.198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.617\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale body mass index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.908\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.763\u0026ndash;1.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.278\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of infertility(primary/ secondary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.409\u0026ndash;3.908\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.683\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntral follicle count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.958\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.858\u0026ndash;1.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.449\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOH protocols\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGnRH-antagonist group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eprogestin-primed ovarian stimulation group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.093\u0026ndash;1.180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emicrostimulation group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.036\u0026ndash;0.654\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEndometriosis is a common gynaecological condition in women of childbearing age. This condition can distort the anatomical structures of the fallopian tubes and ovaries(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), leading to inflammation(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), oxidative damage(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), and harm to oocytes(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), and harm to oocytes(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Currently, laparoscopic enucleation is the preferred treatment modality for ovarian cysts measuring\u0026thinsp;\u0026ge;\u0026thinsp;3 cm in diameter(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, studies have indicated that women who undergo this surgery may respond poorly to Gn stimulation, produce fewer oocytes, and experience DOR, resulting in higher cycle cancellation rates of IVF and embryo transfer cycles as well as lower embryo implantation and clinical pregnancy rates(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Controlled ovulation induction is a crucial step in assisted reproductive technology (ART), and a personalised approach can substantially improve the clinical outcomes of ART. A previous study reported that growth hormone or percutaneous androgen supplementation during ovulation induction therapy significantly improved the cumulative pregnancy rate and live birth rate in patients with a poor ovarian response(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Currently, ovulation induction protocols commonly used in clinical practice for patients with DOR include GnRH antagonist, microstimulation, and PPOS protocols. For patients experiencing DOR following laparoscopic cystectomy of ovarial endometrioma, determining how to obtain high-quality oocytes and embryos through appropriate ovulation induction protocols to reduce stress among patients is an urgent problem in clinical practice.\u003c/p\u003e \u003cp\u003eMost studies have indicated that patients with endometriosis should undergo an ultra-long treatment regimen, mainly due to the inhibitory effect of the GnRH agonist on the ectopic endometrial tissue(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). However, a review published in 2021 suggested that the GnRH antagonist or PPOS protocol may be more suitable than ultra-long treatment regimens for patients with endometriosis(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). GnRH antagonists can competitively bind to pituitary GnRH receptors, reducing the secretion of pituitary Gn. Because of their direct antagonist action(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), GnRH antagonists maintain pituitary responsiveness and can thus maximise the ovarian response to Gn.\u003c/p\u003e \u003cp\u003eA retrospective study conducted in China in 2019(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) compared the assisted reproductive outcomes of patients with endometriosis using GnRH antagonists, long agonist protocol and prolonged agonist protocol. The results revealed no significant differences in hCG positivity, clinical pregnancy, and total embryo implantation rates among the three groups. However, among patients with DOR, the GnRH antagonist group had a higher viable embryo rate than did the rectangular regimen group, and both the total numbers of Gn administration and medication days were lower in the GnRH antagonist group than in the other two groups. The use of GnRH antagonists in patients with endometriosis and infertility resulted in similar pregnancy outcomes as the rectangular and ultra-long regimens. However, GnRH antagonists reduced treatment costs and time and resulted in a higher viable embryo rate. A meta-analysis(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) published in 2022 included 13,050 cycles, with 5,984 patients using a GnRH antagonist and 7,066 patients not using an antagonist. The results demonstrated that the use of a GnRH antagonist was associated with higher live birth rates. Moreover, a significant improvement in live birth rates was noted in women with an AMH level of \u0026lt;\u0026thinsp;1 ng/mL and women aged\u0026thinsp;\u0026ge;\u0026thinsp;35 years. The findings indicate that the use of GnRH antagonists significantly reduces the cycle cancellation rate and increases the number of frozen embryos, possibly due to improvements in embryo quality and endometrial receptivity. This finding is consistent with the results of the present study, which demonstrated that the GnRH antagonist group had a higher rate of high-quality embryos than did the microstimulation group.\u003c/p\u003e \u003cp\u003eIn 2015, Yanping Kuang(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) first proposed the PPOS protocol, which involves adding exogenous progesterone during the follicular phase. A meta-analysis published in 2021(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) reported that in the DOR population, the PPOS protocol resulted in a lower incidence of early-onset luteinising hormone (LH) peaks and ovarian hyperstimulation syndrome than did the GnRH antagonist regimen, GnRH agonist regimen, and natural cycle.\u003c/p\u003e \u003cp\u003eThe results of this study revealed no significant difference in the cumulative pregnancy rate among the three groups. However, the cumulative live birth rate was higher in the GnRH antagonist and PPOS groups than in the microstimulation group. This finding is similar to that of a retrospective study(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) conducted in China in 2020, which included 285 patients according to the Poseidon standard. The results showed that the cumulative clinical pregnancy rate was higher in the GnRH antagonist group than in the microstimulation and PPOS groups. Moreover, in the present study, the numbers of retrieved eggs and 2PN embryos in the GnRH antagonist group were higher than those in the other two groups. This finding may be associated with the larger dosage and longer duration of Gn treatment in the GnRH antagonist protocol, which provides more opportunities for follicular recruitment and growth. Thus, for patients with DOR following laparoscopic cystectomy of ovarial endometrioma, the GnRH antagonist protocol is a more suitable ovulation induction regimen than the microstimulation protocol.\u003c/p\u003e \u003cp\u003eIn 2019, a domestic meta-analysis(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) included 2,270 cycles in the PPOS group and 2,463 cycles in the microstimulation group. The results revealed that for patients with DOR, the PPOS protocol resulted in a higher rate of high-quality embryos and a lower rate of cycle cancellation than did the microstimulation protocol. This finding is consistent with the results of the present study. The microstimulation protocol, which does not involve downregulation, is prone to premature LH peaks and follicular ovulation, resulting in a higher rate of cycle cancellation. However, the results of this study indicate that compared with the microstimulation protocol, the PPOS protocol led to a higher cumulative activity rate. Therefore, the PPOS protocol resulted in better clinical outcomes in the patients included in the current study.\u003c/p\u003e \u003cp\u003eThe results of this study are inconsistent with those of a retrospective study(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) published in 2018, which included 186 POR patient cycles from 2014 to 2016. The results showed that the PPOS protocol resulted in a higher clinical pregnancy rate and live birth rate than did the GnRH antagonist protocol. The inconsistency in findings may be attributable to differences in the included population and sample size between the previous and current study.\u003c/p\u003e \u003cp\u003eFew studies have evaluated the effectiveness of ovulation induction protocols after laparoscopic cystectomy of ovarial endometrioma. This study included patients experiencing DOR after laparoscopic cystectomy of ovarial endometrioma and investigated the effectiveness of PPOS, microstimulation, and GnRH antagonist protocols by determining the cumulative live birth rate. A limitation of this study is the small sample size, which may have led to the lack of significant differences between the main observation indicators of this study. As of the data collection period, there were still many embryos that were frozen and had not been transferred or had not yet resulted in a live birth following successful pregnancy. Furthermore, some patients were still pregnant. Further follow-up is essential to obtain more informative results. In addition, ovarian cysts are highly complex in nature. More research is needed to determine the optimal ovulation induction plan for patients following ovarian cyst surgery.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFor patients aged under 40 years who experienced DOR after laparoscopic cystectomy of ovarial endometrioma, the clinical outcomes of the three ovarian induction protocols were similar. However, the cumulative live birth rate was higher in the GnRH antagonist and PPOS groups than in the microstimulation group.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGn \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;gonadotropin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGnRH \u0026nbsp; \u0026nbsp; gonadotropin releasing hormone\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePPOS \u0026nbsp; \u0026nbsp; progestin-primed ovarian stimulation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDOR \u0026nbsp; \u0026nbsp; \u0026nbsp;diminished ovarian reserve\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIVF \u0026nbsp; \u0026nbsp; \u0026nbsp; in vitro fertilization\u003c/p\u003e\n\u003cp\u003eICSI \u0026nbsp; \u0026nbsp; \u0026nbsp;intracytoplasmic sperm injection\u003c/p\u003e\n\u003cp\u003eAMH \u0026nbsp; \u0026nbsp; anti-Mullerian hormone\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAFC \u0026nbsp; \u0026nbsp; \u0026nbsp;antral follicle count\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFSH \u0026nbsp; \u0026nbsp; \u0026nbsp;follicle-stimulating hormone\u003c/p\u003e\n\u003cp\u003eBMI \u0026nbsp; \u0026nbsp; \u0026nbsp;body mass index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ehCG \u0026nbsp; \u0026nbsp; \u0026nbsp;human chorionic gonadotropin\u003c/p\u003e\n\u003cp\u003eFET \u0026nbsp; \u0026nbsp; \u0026nbsp;frozen\u0026ndash;thawed embryo transfer\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2PN \u0026nbsp; \u0026nbsp; \u0026nbsp;two pronuclear\u003c/p\u003e\n\u003cp\u003eLH \u0026nbsp; \u0026nbsp; \u0026nbsp; luteinising hormone\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful to physicians and coordinators who enrolled patients and collected data from all women who participated in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYJL,JL, JHL,YCG contributed to the conception and design of the study. MNL,XLZ,WZ was involved in the acquisition of data collection .YJL, JWZ,YCZ analyzed data and drafted the manuscript. All authors revised the article and gave their final approval of the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by National Key R\u0026amp;D Program \u0026quot;Fertility Health and Health Security for Women and Children\u0026quot;: Clinical Cohort and Intervention Study on Genetic Problems in Assisted Reproduction Offspring (No:2021YFC2700602), the Medical Science and Technology Research Project of Henan Province (Joint Construction) (No:LHGJ20190365).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the ethics committee of the Third Affiliated Hospital of Zhengzhou University and performed in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have nothing to disclose.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eProfessional Committee on Reproductive Medicine CMDA. Guideline for the diagnosis and treatment of endometriosis (Third edition). Chinese Journal of Obstetrics and Gynecology. 2021;56(12):812-24.\u003c/li\u003e\n\u003cli\u003eRecommendations for the Surgical Treatment of Endometriosis. Part 1: Ovarian Endometrioma. Human Reproduction Open. 2017.\u003c/li\u003e\n\u003cli\u003eDunselman G, Vermeulen N, Becker C, Calhaz-Jorge C, Nelen W. ESHRE guideline: Management of women with endometriosis. Human Reproduction. 2014;29(3).\u003c/li\u003e\n\u003cli\u003eRuiz-Flores FJ, Garcia-Velasco JA. Is there a benefit for surgery in endometrioma-associated infertility? Current Opinion in Obstetrics \u0026amp; Gynecology. 2012;24(3):136-40.\u003c/li\u003e\n\u003cli\u003eBenaglia L, Somigliana E, Vighi V, Ragni G, Vercellini P, Fedele L. Rate of severe ovarian damage following surgery for endometriomas. Human Reproduction. 2010;25(3):678-82.\u003c/li\u003e\n\u003cli\u003eReserve； EGoCoCDMoDO, Association REFPSoCSoFPuCPM. Consensus on clinical diagnosis and management of diminished ovarian reserve. Journal of Reproductive Medicine. 2022;31(4):10.\u003c/li\u003e\n\u003cli\u003eC NPP, A B, Panagiotis Drakopoulos BDE, F JP, Antonio Pellicer G, Samuel Santos-Ribeiro BDH, Herman Tournaye BD, et al. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for invitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including 15,000 women. Fertility and Sterility. 2018;110(4):661-70.\u003c/li\u003e\n\u003cli\u003eProfessional Committee on Reproductive Medicine CMDA. Cumulative delivery/live birth rate of complete ovarian stimulation cycle consensus. Chinese Journal of Reproduction and Contraception. 2018;38(12):6.\u003c/li\u003e\n\u003cli\u003eYoung, Vicky, J., Brown, Jeremy, K., et al. The role of the peritoneum in the pathogenesis of endometriosis. Human Reproduction Update. 2013.\u003c/li\u003e\n\u003cli\u003eGazvani R, Templeton A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction. 2002;123(2):217.\u003c/li\u003e\n\u003cli\u003eHarada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertility and Sterility. 2001;76(1):1-10.\u003c/li\u003e\n\u003cli\u003eA SM, B BS. Oxidative stress status in normal ovarian cortex surrounding ovarian endometriosis. Fertility and Sterility. 2010;93(7):2431-2.\u003c/li\u003e\n\u003cli\u003eGupta S. Impact of ovarian endometrioma on assisted reproduction outcomes. Reproductive Biomedicine Online. 2006;13.\u003c/li\u003e\n\u003cli\u003eBusacca M, Vignali M. Ovarian endometriosis: from pathogenesis to surgical treatment. Current Opinion in Obstetrics \u0026amp; Gynecology. 2003;15(4):321.\u003c/li\u003e\n\u003cli\u003eUrman B, Alper E, Yakin K, Oktem O, Aksoy S, Alatas C, et al. Removal of unilateral endometriomas is associated with immediate and sustained reduction in ovarian reserve. Reproductive Biomedicine Online. 2013;27(2):212-6.\u003c/li\u003e\n\u003cli\u003eJeve YB, Bhandari HM. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis. J Hum Reprod Sci. 2016;9(2):70-81.\u003c/li\u003e\n\u003cli\u003eLive birth rate comparison of three controlled ovarian stimulation protocols for in vitro fertilization-embryo transfer in patients with diminished ovarian reserve after endometrioma cystectomy: a retrospective study. Journal of Ovarian Research. 2020;13(1):1-8.\u003c/li\u003e\n\u003cli\u003eAta B, Telek SB. Assisted reproductive technology for women with endometriosis, a clinically oriented review. Curr Opin Obstet Gynecol. 2021;33(3):225-31.\u003c/li\u003e\n\u003cli\u003eC. B, Lambalk, F. R, Banga, J. A, Huirne, et al. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Human Reproduction Update. 2017.\u003c/li\u003e\n\u003cli\u003eYa Y, Kai W, Qiuping Y, Shen T, Kun L, Liming Z, et al. Controlled ovarian stimulation protocols in endometriosis patients: with antagonist or agonist? Journal of Zhejiang University (Medical Sciences). 2019;48(2):165-73.\u003c/li\u003e\n\u003cli\u003eHurley EG, Sun F, Zhang H, Polotsky AJ, Rios JS. MINIMAL STIMULATION USING GONADOTROPIN-RELEASING HORMONE ANTAGONIST IS ASSOCIATED WITH HIGHER LIVE BIRTH RATES: A NATIONAL STUDY OF 13,050 CYCLES. Fertility and Sterility. 2020;114(3):e286-.\u003c/li\u003e\n\u003cli\u003eYanping, Kuang, Qiuju, Chen, Yonglun, Fu, et al. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertility \u0026amp; Sterility. 2015.\u003c/li\u003e\n\u003cli\u003eGuan S, Feng Y, Huang Y, Huang J. Progestin-Primed Ovarian Stimulation Protocol for Patients in Assisted Reproductive Technology: A Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2021;12:702558.\u003c/li\u003e\n\u003cli\u003eJuan Z, Liming Z, Yiting S, Aili X, Mai L, Kun L. Comparison of the clinical outcomes of three ovulation induction protocols in elderly patients with decline in ovarian reserve. Chinese Journal of Reproduction and Contraception. 2020;40(3):194-200.\u003c/li\u003e\n\u003cli\u003eXin-yue H, Yi-hua Y, Yu F, Ai-ping QN. Application effect of progestin-primed ovarian stimulation and micro-stimulation protocol for patients with poor ovarian response in IVF-ET treatment:a Meta analysis. Journal of Reproductive Medicine. 2019;28(10):1212-8.\u003c/li\u003e\n\u003cli\u003eHuang P, Tang M, Qin A. Progestin-primed ovarian stimulation is a feasible method for poor ovarian responders undergoing in IVF/ICSI compared to a GnRH antagonist protocol: A retrospective study. Journal of Gynecology Obstetrics \u0026amp; Human Reproduction. 2018.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"reproductive-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"reph","sideBox":"Learn more about [Reproductive Health](http://reproductive-health-journal.biomedcentral.com)","snPcode":"12978","submissionUrl":"https://submission.nature.com/new-submission/12978/3","title":"Reproductive Health","twitterHandle":"@Reprod_Health","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"diminished ovarian reserve, ovarial endometrioma, cumulative live birth rate","lastPublishedDoi":"10.21203/rs.3.rs-3124568/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3124568/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003eTo compare the assisted reproductive outcomes of gonadotropin (Gn)-releasing hormone (GnRH) antagonist, microstimulation, and progestin-primed ovarian stimulation (PPOS) protocols in patients with diminished ovarian reserve (DOR) following laparoscopic cystectomy of ovarial endometrioma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003eIn this retrospective cohort study, 89 patients with DOR who had undergone in vitro fertilisation/intracytoplasmic sperm injection at the Department of Reproductive Medicine at the Third Affiliated Hospital of Zhengzhou University from 1 January 2018 to 31 December 2020 were included. According to the controlled ovarian hyperstimulation protocols employed, the patients were divided into GnRH antagonist (38 patients), PPOS (27 patients), and microstimulation (24 patients) groups. The basic data and clinical outcomes of the three groups were compared. The main outcome measure was the cumulative live birth rate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eNo significant differences in the age of the female patients and their spouses and female patients’ body mass index and basal endocrine levels (follicle-stimulating hormone and oestradiol) were noted among the three groups (P \u0026gt; 0.05). The GnRH antagonist group had higher antral follicle counts, greater endometrial thickness on the human chorionic Gn injection day, greater number of oocytes retrieved, and higher two pronuclear embryo counts than did the other two groups. However, the starting dosage of Gn was lower in the GnRH antagonist group than in the other two groups. The microstimulation group had a significantly higher oocyte output rate and high-quality embryo rate than did the other two groups (P \u0026lt; 0.05). No significant differences in the total dosage of Gn, cumulative pregnancy rate, cumulative live birth rate, viable embryo rate, and blastocyst formation rate were observed among the three groups (P \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e For patients aged under 40 years who experienced DOR following laparoscopic cystectomy of ovarial endometrioma, the clinical outcomes of the three controlled ovarian hyperstimulation protocols were similar. However, the cumulative live birth rate was higher in the GnRH antagonist and PPOS groups than in the microstimulation group.\u003c/p\u003e","manuscriptTitle":"Analysis of cumulative live birth rate outcomes of three controlled ovarian hyperstimulation protocols in patients with diminished ovarian reserve following laparoscopic cystectomy of ovarial endometrioma: A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-07-03 13:01:43","doi":"10.21203/rs.3.rs-3124568/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-07-26T00:21:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-07-21T05:39:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"34770c69-ec36-4cfb-97d0-f49b71388886","date":"2023-07-15T00:52:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-07-14T23:36:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-06-30T06:42:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-06-30T06:42:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Reproductive Health","date":"2023-06-29T11:50:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"reproductive-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"reph","sideBox":"Learn more about [Reproductive Health](http://reproductive-health-journal.biomedcentral.com)","snPcode":"12978","submissionUrl":"https://submission.nature.com/new-submission/12978/3","title":"Reproductive Health","twitterHandle":"@Reprod_Health","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6c9d56f9-6638-48b6-b3a7-43b0f43f8580","owner":[],"postedDate":"July 3rd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-09-07T15:11:18+00:00","versionOfRecord":{"articleIdentity":"rs-3124568","link":"https://doi.org/10.1186/s12978-023-01671-3","journal":{"identity":"reproductive-health","isVorOnly":false,"title":"Reproductive Health"},"publishedOn":"2023-08-29 15:08:47","publishedOnDateReadable":"August 29th, 2023"},"versionCreatedAt":"2023-07-03 13:01:43","video":"","vorDoi":"10.1186/s12978-023-01671-3","vorDoiUrl":"https://doi.org/10.1186/s12978-023-01671-3","workflowStages":[]},"version":"v1","identity":"rs-3124568","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3124568","identity":"rs-3124568","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}