Associations of menstrual cycle length with GDM and gestational hypertension in frozen embryo transfer

This retrospective cohort study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [ 11 ], and approved by the Institutional Review Board of Ruijin Hospital (Medical Reaserch-31–24–006223). Between January 2015 and December 2022, 3,285 patients underwent FET at the Reproductive Medical Center of Ruijin Hospital, affiliated with the Shanghai Jiao Tong University School of Medicine, and subsequently delivered singleton infants. The inclusion criteria included comprehensive records of menstrual cycle data, covariates, and follow-up information on pregnancy complications and birth outcomes. Figure  1 illustrates a flowchart of the study population. Fig. 1 Flowchart of the study population Flowchart of the study population To minimize the negative effects on pregnancy outcomes, patients with preexisting medical comorbidities (such as diabetes, hypertension, hyperlipidemia, pituitary disease, and thyroid disease) were excluded, along with those diagnosed with PCOS, uterine factor infertility, or decreased ovarian reserve (including cases involving donor oocytes). The diagnosis of PCOS was confirmed using the Rotterdam criteria [ 12 ]. The covariate data were obtained from a prospectively maintained institutional database and included baseline characteristics, such as pre-pregnancy menstrual cycle data, maternal age, body mass index (BMI), previous parity, causes of infertility, duration of infertility, fertilization method (conventional IVF or ICSI), ovarian stimulation protocol type (GnRH agonist/antagonist, progestin-primed/luteal phase ovarian stimulation, and other protocol), number of transferable embryos, endometrial preparation method (natural cycle or hormone replacement therapy), embryo stage (cleavage or blastocyst), number of embryos transferred, and male partner age. Because the impact of oral contraceptives on IVF pregnancy outcomes remains controversial [ 13 , 14 ], and all patients in this study were confirmed not to have used oral contraceptives for at least 3 months prior to FET, their use was not considered a confounding factor. Based on previous studies [ 3 , 6 , 8 ], participants were categorized into four groups: individuals with shorter cycles (≤ 27days), those with very regular cycles (28–31 days), those with cycle lengths of 32–35 days, and those with prolonged cycles (≥ 36 days). Prolonged cycles included self-reported cycle lengths of 36 days or more, cycles that were too irregular to be estimated, or physician-diagnosed oligomenorrhea [ 15 ]. After controlled ovarian stimulation, the oocytes were retrieved using transvaginal ultrasound. Embryos were graded and cryopreserved 3, 5, or 6 d later using a commercial kit (Kitazato, VT101). Endometrial preparation for FET was achieved through natural cycles or hormone replacement protocols. Progesterone was administered via a vaginal gel when the endometrial thickness reached at least 8 mm. Cleavage-stage embryos were transferred on the fourth day, and blastocysts were transferred on the sixth day of progesterone treatment. Embryos were thawed using a commercial kit (VT102; Kitazato). Serum β-HCG levels were tested 9–14 days post-transfer to confirm biochemical pregnancy. If pregnancy occurred, the progestin treatment was continued until the 10th week of gestation. Data on pregnancy complications and birth outcomes, including GDM, gestational hypertension, preeclampsia, preterm prelabor rupture of membranes, preterm birth (< 37 weeks), very preterm birth (< 32 weeks), high birth weight (≥ 4000 g), low birth weight (< 2500 g), neonatal malformations, and neonatal mortality, were collected from the institutional database. Diagnostic criteria for pregnancy outcomes are presented in Supplemental Table 1. Continuous variables with a normal distribution were expressed as mean ± standard deviation (SD), while non-normally distributed continuous variables were presented as median and interquartile range (IQR). ANOVA was used for normally distributed variables and the Kruskal–Wallis test for non-normally distributed variables. Covariates included in the regression models as potential confounders were age, BMI, parity, causes of infertility, duration of infertility, fertilization method, ovarian stimulation protocol type, number of transferable embryos, endometrial preparation method, embryo stage, and MCL. Univariate analysis was conducted to assess the relationships between the various influencing factors and pregnancy outcomes. These associations were analyzed using odds ratios (ORs) and 95% confidence intervals (CIs). After identifying potential confounders, logistic regression analyses were performed to investigate the effects of a prolonged cycle length on pregnancy complications. All analyses were conducted using SPSS software (version 29.0), with statistical significance set at P  < 0.05.

The baseline characteristics of the 2,543 participants are presented in Table  1 . Participants were grouped into four groups: 208 (8.2%) with shorter cycles, 1,801 (70.8%) with 28–31 days cycles, 264 (10.4%) with 32–35 days cycles, and 270 (10.6%) with prolonged cycles (≥ 36 days). Significant differences in several baseline characteristics were observed across the groups. Participants with prolonged cycles (≥ 36 days) exhibited the highest BMI (22.49 ± 2.83, P  < 0.001) and were most likely to undergo hormone replacement therapy for endometrial preparation (95.2%, P  = 0.001). Maternal age at the time of FET also significantly differed, with participants in the shorter cycle group being the oldest (32.68 ± 4.40 years, P  = 0.007) compared to the other three groups. Similarly, male partner age was significantly higher in the shorter cycle group (34.47 ± 5.36 years, P  = 0.012). Participants with shorter cycles also showed the highest rate of previous parity (17.3%, P  = 0.014) and the fewest transferable embryos (4.6 ± 2.8, P  < 0.001). A significant difference was also observed in the duration of infertility between the groups ( P  = 0.015). However, the fertilization method, infertility diagnosis, type of stimulation protocol, embryo stage at transfer, and number of embryos transferred did not differ. Table 1 Baseline characteristics ( n  = 2543) Characteristic MCL ≤ 27 ( n  = 208) MCL = 28–31 ( n  = 1801) MCL = 32–35 ( n  = 264) MCL ≥ 36 ( n  = 270) P value Age [years] (mean (SD)) 32.7 (4.4) 31.9 (4.2) 31.4 (3.7) 31.7 (4.4) 0.007 BMI [kg/m 2 ] (mean (SD)) 21.9 (2.7) 21.8 (2.7) 21.9 (2.6) 22.5 (2.9) < 0.001 Male partner age [years] (mean (SD)) 34.5 (5.4) 33.8 (5.4) 32.9 (4.6) 33.5 (5.8) 0.012 Duration of infertility [years] (median (IQR)) 3 (2, 5) 3 (1, 4) 3 (2, 4) 3 (2, 5) 0.015 Parity, n (%) 0.014  Primiparous ( P  = 0) 172 (82.7) 1612 (89.5) 236 (89.4) 232 (85.9)  Multiparous ( P  ≥ 1) 36 (17.3) 189 (10.5) 28 (10.6) 38 (14.1) Infertility diagnosis, n (%) 0.900  Tubal factor/ endometriosis 131 (63.0) 1123 (62.4) 164 (62.1) 169 (62.6)  Male factor 66 (31.7) 583 (32.4) 91 (34.5) 89 (33.0)  Unexplained 11 (5.3) 95 (5.3) 9 (3.4) 12 (4.4) Fertilization method, n (%) 0.211  ICSI 56 (26.9) 592 (32.9) 95 (36.0) 90 (33.3)  IVF 152 (73.1) 1209 (67.1) 169 (64.0) 194 (66.7) Type of protocol, n (%) 0.106  GnRH agonist 5 (2.4) 98 (5.4) 10 (3.8) 13 (4.8)  GnRH antagonist 73 (35.1) 777 (43.1) 116 (43.9) 125 (46.3)  PPOS 84 (40.4) 661 (36.7) 103 (39.0) 99 (36.7)  LPOS 10 (4.8) 57 (3.2) 8 (3.0) 6 (2.2)  Other 36 (17.3) 208 (11.5) 27 (10.2) 27 (10.0) No of embryos transferable, (mean (SD)) 4.6 (2.8) 5.4 (3.0) 6.2 (3.1) 5.6 (3.1) < 0.001 Endometrial preparation method, n (%) 0.001  NC 25 (12.0) 240 (13.3) 31 (11.7) 13 (4.8)  HRT 183 (88.0) 1561 (86.7) 233 (88.3) 257 (95.2) Embryo stage, n (%) 0.134  Cleavage 117 (56.3) 864 (48.0) 125 (47.3) 127 (47.0)  Blastocyst 91 (43.7) 937 (52.0) 139 (52.7) 143 (53.0) Number of embryos transferred, n (%) 0.226  1 83 (39.9) 776 (43.1) 104 (39.4) 128 (47.4)  2 125 (60.1) 1025 (56.9) 160 (60.6) 142 (52.6) MCL menstrual cycle length, BMI body mass index, IVF in vitro fertilization, ICSI intracytoplasmic sperm injection, PPOS Progestin-Primed Ovarian Stimulation, LPOS Luteal Phase Ovarian Stimulation, NC natural cycle, HRT hormone replacement therapy, SD standard deviation, IQR interquartile range Statistically significant p -values are shown in bold Baseline characteristics ( n  = 2543) MCL menstrual cycle length, BMI body mass index, IVF in vitro fertilization, ICSI intracytoplasmic sperm injection, PPOS Progestin-Primed Ovarian Stimulation, LPOS Luteal Phase Ovarian Stimulation, NC natural cycle, HRT hormone replacement therapy, SD standard deviation, IQR interquartile range Statistically significant p -values are shown in bold We documented pregnancy outcomes during the 8 years of follow-up. Analysis of pregnancy complications and birth outcomes across the different MCL groups is summarized in Table  2 . Women with prolonged cycles (≥ 36 days) showed a significantly higher incidence rate of GDM (25.6%, P  < 0.001) than the other groups. Gestational hypertension was most frequently reported in women with prolonged menstrual cycles (12.2%; P  = 0.01). Other pregnancy complications and birth outcomes did not differ significantly among the four groups. Table 2 Comparison of pregnancy complications and birth outcomes in different MCL groups Pregnancy outcome MCL ≤ 27 ( n  = 208) MCL = 28–31 ( n  = 1801) MCL = 32–35 ( n  = 264) MCL ≥ 36 ( n  = 270) P value GDM, n (%) 22 (10.6) 325 (18.0) 43 (16.3) 69 (25.6) < 0.001 Gestational hypertension, n (%) 15 (7.2) 125 (6.9) 27 (10.2) 33 (12.2) 0.010 Preeclampsia, n (%) 5 (2.4) 38 (2.1) 4 (1.5) 7 (2.6) 0.808 PPROM, n (%) 3 (1.4) 51 (2.8) 6 (2.3) 3 (1.1) 0.263 PTB < 37wk, n (%) 12 (5.8) 148 (8.2) 14 (5.3) 17 (6.3) 0.201 PTB < 32wk, n (%) 1 (0.5) 20 (1.1) 2 (0.8) 3 (1.1) 0.933 High birth weight, n (%) 30 (14.4) 176 (9.8) 20 (7.6) 25 (9.3) 0.088 Low birth weight, n (%) 8 (3.8) 90 (5.0) 10 (3.8) 12 (4.4) 0.749 Neonatal malformation, n (%) 5 (2.2) 33 (1.8) 6 (2.2) 9 (3.2) 0.411 Neonatal mortality, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) NA High birth weight ≥ 4000 g, Low birth weight < 2500 g MCL menstrual cycle length, GDM gestational diabetes mellitus, PPROM preterm prelabor rupture of membranes, PTB preterm birth, NA not available Statistically significant p-values are shown in bold Comparison of pregnancy complications and birth outcomes in different MCL groups High birth weight ≥ 4000 g, Low birth weight < 2500 g MCL menstrual cycle length, GDM gestational diabetes mellitus, PPROM preterm prelabor rupture of membranes, PTB preterm birth, NA not available Statistically significant p-values are shown in bold Univariate analyses of GDM and gestational hypertension were conducted across several variables and the results are shown in Table  3 . Increased maternal age and BMI were significantly associated with a higher risk of GDM and gestational hypertension. For GDM, each additional year of age raised the risk by 9% (OR 1.09, 95% CI 1.06–1.11, P  < 0.001), while each unit increase in BMI increased the risk by 6% (OR 1.06, 95% CI 1.03–1.10, P  < 0.001). Table 3 Results of univariate analysis of GDM and Gestational hypertension Variable GDM Gestational hypertension OR (95% CI) P value OR (95% CI) P value Age (years) 1.09 (1.06–1.11) < 0.001 1.04 (1.01–1.08) 0.013 BMI (kg/m 2 ) 1.06 (1.03–1.10) < 0.001 1.13 (1.08–1.19) < 0.001 Male partner age (years) 1.05 (1.03–1.07) < 0.001 1.02 (0.99–1.05) 0.170 Duration of infertility (years) 1.04 (0.99–1.08) 0.063 1.04 (0.99–1.09) 0.148 Parity   P  = 0 1 1   P  ≥ 1 0.77 (0.54–1.08) 0.124 1.23 (0.80–1.88) 0.342 Infertility diagnosis  Male factor 1 1  Tubal factor/endometriosis 1.27 (1.01–1.59) 0.042 0.89 (0.66–1.22) 0.473  Unexplained 1.68 (1.07–2.63) 0.024 1.15 (0.60–2.19) 0.672 Fertilization method  ICSI 1 1  IVF 1.24 (0.99–1.55) 0.057 1.12 (0.82–1.53) 0.479 Type of protocol  GnRH agonist 1 1  GnRH antagonist 1.00 (0.62–1.63) 0.990 0.89 (0.45–1.77) 0.747  PPOS 1.11 (0.68–1.81) 0.677 1.04 (0.52–2.07) 0.908  LPOS 1.16 (0.57–2.38) 0.678 1.63 (0.65–4.12) 0.298  Other 0.95 (0.55–1.65) 0.864 1.02 (0.47–2.19) 0.968  No of embryos transferable 0.99 (0.96–1.03) 0.825 0.97 (0.92–1.02) 0.165 Endometrial preparation method  NC 1 1  HRT 0.88 (0.65–1.19) 0.410 2.08 (1.17–3.67) 0.013 Embryo stage  Cleavage 1 1  Blastocyst 1.13 (0.92–1.39) 0.234 0.94 (0.70–1.25) 0.655 Number of embryos transferred  1  2 MCL (days)  ≤ 27 0.54 (0.34–0.85) 0.008 1.04 (0.60–1.82) 0.884  28–31 1 1  32–35 0.88 (0.62–1.25) 0.486 1.53 (0.99–2.37) 0.058  ≥ 36 1.56 (1.16–2.10) 0.004 1.87 (1.24–2.81) 0.003 GDM gestational diabetes mellitus, BMI body mass index, IVF in vitro fertilization, ICSI intracytoplasmic sperm injection, PPOS Progestin-Primed Ovarian Stimulation, LPOS Luteal Phase Ovarian Stimulation, NC natural cycle, HRT hormone replacement therapy, MCL menstrual cycle length, OR odds ratio, 95% CI confidence interval Statistically significant p -values are shown in bold Results of univariate analysis of GDM and Gestational hypertension GDM gestational diabetes mellitus, BMI body mass index, IVF in vitro fertilization, ICSI intracytoplasmic sperm injection, PPOS Progestin-Primed Ovarian Stimulation, LPOS Luteal Phase Ovarian Stimulation, NC natural cycle, HRT hormone replacement therapy, MCL menstrual cycle length, OR odds ratio, 95% CI confidence interval Statistically significant p -values are shown in bold For gestational hypertension, the risk rose by 4% per year of age (OR 1.04, 95% CI 1.01–1.08, P  = 0.013) and by 13% per unit of BMI (OR 1.13, 95% CI 1.08–1.19, P  < 0.001). Participants with prolonged menstrual cycles (≥ 36 days) showed higher risks of both GDM (OR 1.56, 95% CI 1.16–2.10, P  = 0.004) and gestational hypertension (OR 1.87, 95% CI 1.24–2.81, P  = 0.003) compared to the very regular cycle group (28–31 days). Those with shorter cycles (≤ 27 days) had reduced risk of GDM (OR 0.54, 95% CI 0.34–0.85, P  = 0.008), but showed no significant association with gestational hypertension. Additionally, tubal factor or endometriosis-induced infertility was associated with a higher risk of GDM (OR 1.27, 95% CI 1.01–1.59, P  = 0.042), and participants with unexplained infertility also demonstrated an elevated risk of GDM (OR 1.68, 95% CI 1.07–2.63, P  = 0.024). The use of hormone replacement therapy was notably associated with an increased risk of gestational hypertension (OR 2.08, 95% CI 1.17–3.67, P  = 0.013). Univariate analysis revealed that GDM was associated with maternal age, higher BMI, prolonged menstrual cycles (≥ 36 days), and specific infertility causes (tubal/endometriosis and unexplained), with short cycles (≤ 27 days) being protective. Gestational hypertension was significantly related to maternal age, higher BMI, prolonged menstrual cycles (≥ 36 days), and the use of hormone replacement therapy. The logistic regression analysis was conducted to evaluate the robustness of the associations between MCL and two pregnancy outcomes: GDM and gestational hypertension. The analysis was adjusted for relevant covariates including age, BMI, and other relevant factors for each outcome. As presented in Fig.  2 A, women with prolonged cycles (≥ 36 days) had a significantly higher adjusted odds ratio (aOR) for 1.54 (95% CI: 1.14–2.09, P  = 0.006) for developing GDM compared to those with MCL between 28 and 31 days. Women with shorter cycles (≤ 27 days) had a lower risk (aOR 0.49, 95% CI: 0.31–0.78, P  = 0.003). For gestational hypertension, MCL of 32–35 and ≥ 36 days were associated with higher risks, with aORs of 1.59 (95% CI: 1.02–2.48, P  = 0.041) and 1.60 (95% CI: 1.05–2.42, P  = 0.027), respectively (Fig.  2 B). Fig. 2 Multivariable regression analysis of GDM and Gestational hypertension. A GDM. B Gestational hypertension Multivariable regression analysis of GDM and Gestational hypertension. A GDM. B Gestational hypertension

Prolonged or irregular menstrual cycles are indicative of female infertility [ 1 , 2 ], and have been associated with cardiometabolic conditions [ 3 ]. Menstrual irregularities, which affect approximately 22–30% of women of reproductive age [ 4 , 5 ], vary depending on population characteristics [ 3 , 5 ]. A normal ovulatory menstrual cycle is a critical sign of women’s overall health, including fertility [ 2 , 5 ]. Several studies have confirmed an association between prolonged or irregular menstrual cycles and an increased risk of gestational diabetes mellitus (GDM) [ 6 – 8 ]. Previous research has reported that women with menstrual cycle length (MCL) ≥ 32 days during mid-adulthood have a higher risk of GDM compared to those with very regular cycles [ 6 ]. Another study found that women who had prolonged menstrual cycles (≥ 36 days) and were either overweight or gained > 5 kg in adulthood had a 4–5-fold higher GDM risk than women who had a normal cycle length and were non-obese or gained < 5 kg in adulthood [ 8 ]. However, the underlying mechanisms remain unclear, and evidence linking prolonged menstrual cycles to pregnancy complications is limited. Women with prolonged or irregular menstrual cycles have a higher demand for assisted reproductive technology (ART) treatments because of elevated infertility risks, which may also contribute to an increased incidence of pregnancy complications [ 9 , 10 ]. In a recent meta-analysis of 37 studies, women with singleton pregnancies achieved using ART showed a higher risk of GDM than those who conceived spontaneously [ 9 ]. In addition, another meta-analysis of 50 studies revealed that ART singleton pregnancies were associated with increased risks of GDM, gestational hypertension, preterm birth, low birth weight, perinatal mortality, and congenital malformations compared to spontaneous conceptions [ 10 ]. The reasons for the higher risk of complications in ART pregnancies are not well understood. Maternal factors related to infertility may explain the increased risk of pregnancy-related complications associated with ART. Despite the existing research, the impact of pre-pregnancy menstrual characteristics on pregnancy outcomes is still unclear. To our knowledge, no previous study has examined the association between MCL and pregnancy complications in women without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) treatment. Thus, in this study, we investigated the potential relationship between MCL, pregnancy complications, and adverse birth outcomes in women undergoing IVF or intracytoplasmic sperm injection (ICSI) with frozen embryo transfer (FET).

In this study, we found that prolonged menstrual cycles (≥ 36 days) were a significant independent risk factor for GDM. Furthermore, MCLs of ≥ 32 days were independently associated with an increased risk of gestational hypertension in women without PCOS undergoing FET, even after adjusting for relevant confounders. Interestingly, shorter menstrual cycles (≤ 27 days) were associated with a lower risk of GDM development. The increased prevalence of GDM among women with prolonged menstrual cycles (≥ 36 days) aligns with previous research in the general population [ 6 , 7 ]. Wang et al. found that women with irregular menstrual cycles in mid-adulthood had a 65% increased risk of GDM compared with those with regular menstrual cycles. The GDM risk was higher among women with MCL usually ≥ 32 days during mid-adulthood, independent of BMI, age, higher parity, and unhealthy lifestyles [ 6 ]. Similarly, a prior small-sample retrospective study demonstrated that menstrual irregularity (absence of monthly menstruation or menstrual intervals ≥ 60 days) was strongly associated with GDM when stratified by BMI [ 7 ]. However, Dishi et al. reported that longer menstrual cycles (≥ 36 days) are significantly associated with a higher risk of GDM, particularly among women who were either overweight or obese pre-pregnancy, or gained more than 5 kg weight gain in adulthood [ 8 ]. These studies generally lacked data on PCOS diagnosis, preventing the determination of whether the associations were solely attributable to the underlying PCOS, which may contribute to the increased risk of GDM. Prolonged menstrual cycles are significantly associated with hyperinsulinemia [ 16 , 17 ], which can inhibit the production of sex hormone-binding globulin, leading to elevated levels of free testosterone [ 18 ], these factors are reported as risk factors for GDM [ 19 – 21 ]. In addition, longer menstrual cycles have been linked to lipid metabolism abnormalities and other metabolic disturbances [ 22 , 23 ], which might contribute to the development of GDM [ 24 , 25 ]. Gestational glucose intolerance has been associated with gestational hypertension independent of obesity and blood glucose levels, which is partly explained by insulin resistance linked to both inflammatory dysregulation and vascular dysfunction [ 26 ]. Our study provides novel evidence that links prolonged menstrual cycles to an increased risk of gestational hypertension. Previous research has identified an association between prolonged menstrual cycles and an increased risk of cardiovascular disease (CVD). A nationwide UK cohort study found that women with long and irregular cycles (> 20 days variation) had a higher cardiometabolic risk. These include composite CVD, ischemic heart disease, heart failure, hypertension, and type 2 diabetes [ 27 ]. Similarly, a US cross-sectional study reported that participants without PCOS but with irregular menstrual cycles had higher odds of developing cardiometabolic conditions, including type 2 diabetes, high cholesterol levels, arrhythmia, and transient ischemic attacks [ 3 ]. One possible explanation for the increased risk of GDM and gestational hypertension among women with prolonged menstrual cycles is that these menstrual irregularities may indicate underlying metabolic abnormalities [ 22 , 23 ], and pro-inflammatory processes [ 28 ], potentially predisposing them to a higher prevalence of cardiometabolic conditions. Importantly, MCL likely reflects a woman’s long-term endocrine and metabolic milieu rather than the characteristics of a specific treatment cycle [ 27 , 29 , 30 ]. Although FET is performed under controlled hormonal conditions, women with prolonged menstrual cycles may have an underlying predisposition to insulin resistance, metabolic dysfunction, and vascular impairment, which could persist during assisted reproductive treatment and contribute to adverse pregnancy outcomes. Pregnant individuals with impaired glucose metabolism or hypertension face a higher risk of complications during pregnancy and later in life, including maternal mortality and morbidity, future cardiometabolic disorders, and negative effects on fetuses and newborns [ 31 , 32 ]. Despite the current lack of robust supporting data, we propose that prolonged menstrual cycles should be considered as a risk factor for infertility in patients undergoing IVF/ICSI-FET, warranting prior screening and early prevention of GDM and gestational hypertension. Incorporating the characteristics of prolonged menstrual cycles and higher BMI into routine medical evaluations before IVF treatment may assist in identifying individuals who could benefit from regular cardiometabolic health assessments. Further metabolic research is required in populations with prolonged menstrual cycles to identify the potential pathophysiological mechanisms that contribute to the increased risk of GDM and gestational hypertension. To the best of our knowledge, this is the first study to demonstrate an association between prolonged prepregnancy menstrual cycles and an increased risk of GDM and gestational hypertension in FET cycles. Moreover, we excluded PCOS and other comorbidities that might affect menstruation to assess the impact of menstrual characteristics on pregnancy outcomes more accurately. To further investigate the influence of unusually long menstrual cycles on pregnancy outcomes, we performed additional supplementary analyses by stratifying the study population into five groups based on the MCL (≤ 27, 28–31, 32–35, 35–59, and ≥ 60 days). In the subgroup with unusually long cycles (≥ 60 days), the risks of GDM (aOR 2.06) and gestational hypertension (aOR 1.88) were elevated, though not statistically significant, which may be due to the very limited sample size in this cohort (Supplemental Tables 2–5). Larger prospective studies are essential to validate our findings and explore methods for preventing pregnancy-related complications. However, our retrospective design has inherent limitations, such as the absence of baseline metabolic data, including insulin and lipid profiles, which prevents further confirmation of the underlying causes of the increased risk of GDM and gestational hypertension. Additionally, our study cohort was limited to individuals who underwent FET cycles; thus, our findings may not be generalizable to those who underwent fresh embryo transfer cycles.

In a large retrospective study, prolonged menstrual cycles significantly increased the risk of GDM and gestational hypertension in women who underwent FET. These findings highlight the need for individualized risk assessment, early identification, and risk stratification in this population. Comprehensive management during IVF pregnancies is essential and focusing on prevention, close monitoring, and early intervention may improve pregnancy outcomes.

Supplementary Material 1. Supplementary Material 1.