Association of ovarian response with anogenital distance in patients undergoing ovarian stimulation for in vitro fertilization/intra cytoplasmic sperm injection: a prospective cohort study
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20260189Keywords:
Anogenital Distance, Ovarian reserve, Ovarian stimulation, Ovarian sensitivity indexAbstract
Background: The study investigates whether Anogenital Distance (AGD), a permanent marker of the prenatal hormonal environment, is associated with established ovarian reserve markers (FSH, AMH, AFC). Crucially, the aim is to determine if AGD can predict Ovarian Sensitivity Index (OSI) and overall ovarian response during controlled ovarian stimulation (COS) for IVF/ICSI.
Methods: This was a prospective cohort study conducted at an Indian IVF Reproductive and Biology Centre, located within the Department of Obstetrics and Gynaecology at Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi (n=40), aiming to evaluate the association of the anogenital distance (AGD), measured using digital calipers, with ovarian response, specifically the ovarian sensitivity index (OSI), and clinical outcomes in infertile women undergoing their first IVF/ICSI cycle.
Results: The study confirmed that age and AFC are inverse determinants of ovarian response, with low responders being older, having lower AFC, and requiring the highest gonadotropin dose. This resulted in highly significant differences (p<0.001) in oocyte yield, embryo formation, and ovarian sensitivity index (OSI), which peaked sharply in high responders (9.50\pm 2.87). Consequently, the clinical strategy varied significantly: Fresh ET dominated in Low/Normo groups, while 83.3% of high responders underwent frozen ET. Critically, the clinical pregnancy rate was highest in Normo Responders (42.8%), showing a statistically significant difference (P=0.03), while anogenital distance (AGD) showed no significant difference across the groups.
Conclusions: This study confirmed that age and poor ovarian reserve (high FSH, low AFC, low OSI) significantly define low responders, leading to inferior IVF cycle productivity compared to normo and high responders. Although anogenital distance (AGD) itself wasn't significantly different between groups, it positively correlated with key ovarian markers (AFC, OSI), suggesting it is a promising but unproven biomarker for ovarian reserve.
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References
Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015;103(3):e9-17. DOI: https://doi.org/10.1016/j.fertnstert.2014.12.093
Hansen KR, Craig LB, Zavy MT, Klein NA, Soules MR. Ovarian primordial and non-growing follicle counts according to the stages of reproductive aging workshop (STRAW) staging system. Menopause. 2012;19(2):164-171. DOI: https://doi.org/10.1097/gme.0b013e31823b0b2e
Ibáñez L, Valls C, Cols M, Ferrer A, Marcos MV, De Zegher F. Hypersecretion of FSH in infant boys and girls born small for gestational age. J Clin Endocrinol Metab. 2002;87(5):1986-8. DOI: https://doi.org/10.1210/jcem.87.5.8459
Mark-Kappeler CJ, Hoyer PB, Devine PJ. Xenobiotic effects on ovarian preantral follicles. Biol Reprod. 2011;85(5):871-83. DOI: https://doi.org/10.1095/biolreprod.111.091173
Souter I, Smith KW, Dimitriadis I, Ehrlich S, Williams PL, Calafat AM, et al. The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments. Reprod Toxicol. 2013;42:224-231. DOI: https://doi.org/10.1016/j.reprotox.2013.09.008
Earl Gray Jr L, Wilson VS, Stoker T, Lambright C, Furr J, Noriega N, et al. Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. Int J Androl. 2006;29(1):96-104. DOI: https://doi.org/10.1111/j.1365-2605.2005.00636.x
Greenham LW, Greenham V. Sexing mouse pups. Lab Anim. 1977;11(3):181-4. DOI: https://doi.org/10.1258/002367777780936620
Kurzrock EA, Jegatheesan P, Cunha GR, Baskin LS. Urethral development in the fetal rabbit and induction of hypospadias: a model for human development. J Urol. 2000;164(5):1786-92. DOI: https://doi.org/10.1016/S0022-5347(05)67107-8
Bornehag CG, Carlstedt F, Jönsson BA, Lindh CH, Jensen TK, Bodin A, et al. Prenatal phthalate exposures and anogenital distance in Swedish boys. Environ Health Perspect. 2015;123(1):101-7. DOI: https://doi.org/10.1289/ehp.1408163
Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect. 2005;113(8):1056-61. DOI: https://doi.org/10.1289/ehp.8100
Mendiola J, Roca M, Mínguez-Alarcón L, Mira-Escolano MP, López-Espín JJ, Barrett ES, et al. Anogenital distance is related to ovarian follicular number in young Spanish women: a cross-sectional study. Environ Health. 2012;11(1):1-8. DOI: https://doi.org/10.1186/1476-069X-11-90
Mendiola J, Sánchez-Ferrer ML, Jimenez-Velazquez R, Canovas-Lopez L, Hernandez-Penalver AI, Corbalan-Biyang S, et al. Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment. Hum Reprod. 2016;31(10):2377-83. DOI: https://doi.org/10.1093/humrep/dew163
Wu Y, Zhong G, Chen S, Zheng C, Liao D, Xie M. Polycystic ovary syndrome is associated with anogenital distance, a marker of prenatal androgen exposure. Hum Reprod. 2017;32(4):937-43. DOI: https://doi.org/10.1093/humrep/dex042
Huber M, Hadziosmanovic N, Berglund L, Holte J. Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol. Fertil Steril. 2013;100(5):1270-6. DOI: https://doi.org/10.1016/j.fertnstert.2013.06.049
Li HW, Lee VC, Ho PC, Ng EH. Ovarian sensitivity index is a better measure of ovarian responsiveness to gonadotrophin stimulation than the number of oocytes during in-vitro fertilization treatment. J Assist Reprod Genet. 2014;31(2):199-203. DOI: https://doi.org/10.1007/s10815-013-0144-5
Badawy A, Wageah A, El Gharib M, Osman EE. Prediction and diagnosis of poor ovarian response: the dilemma. J Reprod Infertil. 2011;12(4):241-8.
Panda N, Giri R, Das S, Pradhan S, Sahu MK. Comparison of the outcome of in vitro fertilization cycles in poor responders and good responders. J Hum Reprod Sci. 2010;3(2):85-9.
Fàbregues F, Balasch J, Creus M, Carmona F. Clinical outcome of in vitro fertilization cycles in women classified as low, normal and high responders according to the Bologna criteria. J Assist Reprod Genet. 2018;35(2):221-6.
Mendiola J, Stahlhut RW, Jørgensen N, Liu F, Swan SH. Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environ Health Perspect. 2011;119(7):958-63. DOI: https://doi.org/10.1289/ehp.1103421
Malin H, Sunkara SK, Raine-Fenning N, La Marca A. A continuous index of ovarian sensitivity to exogenous gonadotrophins. Reprod Biomed Online. 2013;27(1):60-5.
László F, László L, Zoltán B, Sándor M, Zsolt M. Differences in ovarian response, fertilization rate and clinical outcome between poor and normal responders in an in vitro fertilization program. Eur J Obstet Gynecol Reprod Biol. 2002;103(2):125-9.