Determinants of Conception and Adverse Pregnancy Outcomes in Women with Endometriosis: A Longitudinal Study

Endometriosis, affecting approximately 10% of reproductive-aged women globally, poses significant challenges, including chronic pelvic pain, dysmenorrhea, and infertility. In low- and middle-income countries like India, accessibility to affordable infertility care remains a concern. This multicenter prospective cohort study, conducted across six tertiary care hospitals in India from 2017 to 2022, aims to explore the natural progression of conception and pregnancy outcomes in women with endometriosis. Of the 257 participants, 19.1% conceived during the study, revealing significant geographic and income-based variations (p < 0.001, p = 0.01). Dysmenorrhea (p < 0.001) and dyspareunia (p=0.027) were correlated with conception, while no such associations were found with chronic pelvic pain or menstrual factors. Lesion type, number, and severity showed no conclusive link with conception. Natural conception occurred in 70% of cases, with an average post-surgery conception time of 282.1 days. Live birth rate was 85.7%, while complications included placenta previa (16.4%), preeclampsia (4.1%), and preterm births (4.1%). This study, one of the first in India on endometriosis-related fertility progression, emphasizes the need for comprehensive understanding and management of conception and pregnancy outcomes. Considering India's substantial endometriosis burden, the study recommends prioritizing larger multicenter investigations for a better understanding and effective strategies for infertility management. Data Availability The data that support the findings of this study are available from the corresponding author (RKG), upon reasonable request. Data containing information that could compromise participant identity and confidentiality will not be shared. Abbreviations - ART: - Artificial Reproductive Technology - DIE: - Deep Infiltrating Endometriosis - EFI: - Endometriosis Fertility Index - GDM: - Gestational Diabetes Mellitus - IEC: - Institutional Ethics Committee - IUGR: - Intrauterine Growth Restriction - OMA: - Ovarian Endemetrioma - PP: - Placenta previa - rAFS: - Revised American Fertility Society - SUP: - Superficial Peritoneal Endometriosis - WERF EPHect: - World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project

Gajbhiye RK, Montgomery G, Pai MV, Phukan P, Shekhar S, Padte K, et al. Protocol for a case-control study investigating the clinical phenotypes and genetic regulation of endometriosis in Indian women: the ECGRI study. BMJ Open. 2021;11:e050844. https://doi.org/10.1136/bmjopen-2021-050844. Macer ML, Taylor HS. Endometriosis and Infertility. Obstet Gynaecol Clin N Am. 2012;39:535–49. https://doi.org/10.1016/j.ogc.2012.10.002. Farland LV, Prescott J, Sasamoto N, Tobias DK, Gaskins AJ, Stuart JJ, et al. Endometriosis and Risk of Adverse Pregnancy Outcomes. Obstet Gynecol. 2019;134:527–36. https://doi.org/10.1097/AOG.0000000000003410. Saraswat L, Ayansina D, Cooper K, Bhattacharya S, Miligkos D, Horne A, et al. Pregnancy outcomes in women with endometriosis: a national record linkage study. BJOG: Int J Obstet Gy. 2017;124:444–52. https://doi.org/10.1111/1471-0528.13920. Bhurke AV, DasMahapatra P, Balakrishnan S, Khan SA, Mortlock S, Das V, et al. Clinical characteristics and surgical management of endometriosis-associated infertility: A multicenter prospective cohort study. Int J Gynaecol Obstet. 2022;159:86–96. https://doi.org/10.1002/ijgo.14115. Tahmasbi Rad M, Akpinar-Isci D, Nobs T, Gasimli K, Becker S. Pregnancy after laparoscopic surgery for endometriosis: How long should we wait? A retrospective study involving a long-term follow up at a university endometriosis center. Intl J Gynecology & Obste. 2023;163:108–14. https://doi.org/10.1002/ijgo.14849. Qiao X, Wu L, Liu D, Pei T, Huang W. Existence of chronic endometritis and its influence on pregnancy outcomes in infertile women with minimal/mild endometriosis. Intl J Gynecology & Obste. 2023;160:628–34. https://doi.org/10.1002/ijgo.14326. Matsuzaki S, Nagase Y, Ueda Y, Lee M, Matsuzaki S, Maeda M, et al. The association of endometriosis with placenta previa and postpartum hemorrhage: a systematic review and meta-analysis. Am J Obstet Gynecol MFM. 2021;3:100417. https://doi.org/10.1016/j.ajogmf.2021.100417. Drummond K, Danesh NM, Arseneault S, Rodrigues J, Tulandi T, Raina J, et al. Association between Endometriosis and Risk of Preeclampsia in Women Who Conceived Spontaneously: A Systematic Review and Meta-analysis. J Minimal Invasive Gynecol. 2023;30:91–9. https://doi.org/10.1016/j.jmig.2022.11.008. Salmeri N, Li Piani L, Cavoretto PI, Somigliana E, Viganò P, Candiani M. Endometriosis increases the risk of gestational diabetes: a meta-analysis stratified by mode of conception, disease localization and severity. Sci Rep. 2023;13:8099. https://doi.org/10.1038/s41598-023-35236-y. Brønd M, Breintoft K, Forman A, Henriksen TB, Ramlau-Hansen CH, Rytter D, et al. Measures of fetal growth and preterm birth and risk of endometriosis and adenomyosis in adult life: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2023;102:986–99. https://doi.org/10.1111/aogs.14594. Salmeri N, Farina A, Candiani M, Dolci C, Bonavina G, Poziello C, et al. Endometriosis and Impaired Placentation: A Prospective Cohort Study Comparing Uterine Arteries Doppler Pulsatility Index in Pregnancies of Patients with and without Moderate-Severe Disease. Diagnostics (Basel). 2022;12:1024. https://doi.org/10.3390/diagnostics12051024. Scala C, Leone Roberti Maggiore U, Racca A, Barra F, Vellone VG, Venturini PL, et al. Influence of adenomyosis on pregnancy and perinatal outcomes in women with endometriosis. Ultrasound Obstet Gynecol. 2018;52:666–71. https://doi.org/10.1002/uog.18989. Didziokaite G, Biliute G, Gudaite J, Kvedariene V. Oxidative Stress as a Potential Underlying Cause of Minimal and Mild Endometriosis-Related Infertility. Int J Mol Sci. 2023;24:3809. https://doi.org/10.3390/ijms24043809. Buyalos RP, Agarwal SK. Endometriosis-associated infertility. Curr Opin Obstet Gynecol. 2000;12:377–81. https://doi.org/10.1097/00001703-200010000-00006.

The authors thank Dr. Smita Mahale, Dr. Geetanjali Sachdeva, Dr. Neeta Warty, Dr Shahina Begum, Dr. Periyasamy Kuppusamy, Ms. Aishwarya Bhurke, Ms. Merlin Pious, Ms. Sana Shaikh, Ms. Akhila S., staff of HRRC Lucknow, and staff of HRRC Trivandrum. Data collection was facilitated by and conducted in compliance with the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (WERF EPHect). Rahul K Gajbhiye is an awardee of the DBT Wellcome Trust India Alliance Clinical and Public Health Intermediate Fellowship (Grant no. IA/CPHI/18/1/503933). Funding The study was partially funded by Department of Science and Technology, Government of India (EEQ/2016/000206), and ICMR–National Institute for Research in Reproductive and Child Health, Mumbai (ICMR-NIRRCH/MS/RA/1613/09–2023). The funders had no role in designing the study; in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. Author information Authors and Affiliations Contributions Rahul K. Gajbhiye had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualization and funding acquisition: Rahul K. Gajbhiye. Investigation at respective centers: Pramathes Das Mahapatra, Sheila Balakrishnan, Chelana Nirmala, Vinita Das, Ketki Kulkarni, Bimal M John, Amiya Majumdar, CV Sowmini, Aarti Srivastava. Study coordination: Shagufta Khan, Komal Khade, Rahul K. Gajbhiye. Literature review and data analysis: Hrishikesh Munshi, Tabassum Khan. Preparation of original draft of manuscript: Hrishikesh Munshi, Tabassum Khan, Rahul K. Gajbhiye. Revision, editing and approval of final version of manuscript for submission: Hrishikesh Munshi, Tabassum Khan, Shagufta Khan, Pramathes DasMahapatra, Sheila Balakrishnan, Chelana Nirmala, Vinita Das, Ketki Kulkarni, Bimal M John, Amiya Majumdar, CV Sowmini, Aarti Srivastava, Komal Khade, Rahul K Gajbhiye. Corresponding author Ethics declarations Ethics Approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Ethics Committee (IEC) of the ICMR-National Institute for Research in Reproductive and Child Health, Mumbai (D/ICEC/Sci-106/143/2016) as well as by the IECs of all participating study sites. Written informed consent were obtained from all participating women. Conflict of Interest The authors declare that they have no conflicts of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information ESM 1 (download DOCX ) (DOCX 30 kb) Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Munshi, H., Khan, T., Khan, S. et al. Determinants of Conception and Adverse Pregnancy Outcomes in Women with Endometriosis: A Longitudinal Study. Reprod. Sci. 31, 1757–1762 (2024). https://doi.org/10.1007/s43032-024-01569-w Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-024-01569-w