Dose Nomogram of Individualization of the Initial Follicle-Stimulating Hormone Dosage for Patients with Polycystic Ovary Syndrome Undergoing IVF/ICSI with the GnRH-Ant Protocol: A Retrospective Cohort Study

Overview

Journal Adv Ther

Date 2023 Jul 3

PMID 37395872

Authors

Manfei Si

Xinyu Qi

Xiumei Zhen

Chen Yang

Tian Tian

Xiaoyu Long

Jie Qiao

Affiliations

Soon will be listed here.

Abstract

Introduction: For high responders with polycystic ovary syndrome (PCOS), there is no clear recommendation for the initial follicle-stimulating hormone (FSH) dosage to ensure an optimal number of retrieved oocytes and avoid ovarian hyperstimulation syndrome (OHSS). The aim of this study was to determine the ideal initial FSH dosage of in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) using the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol to obtain the optimal number of retrieved oocytes and minimize the risk of OHSS.

Methods: The data of 1898 patients with PCOS aged 20-40 years from January 2017 to December 2020 were retrospectively analyzed to explore the factors related to the number of retrieved oocytes. Statistically significant variables were used to construct a dose nomogram and it was then validated using an independent cohort of patients with PCOS from January 2021 to December 2021.

Results: Multivariate analyses demonstrated that body mass index (BMI) was the most significant factor to predict the number of retrieved oocytes compared to body weight (BW) and body surface area (BSA). Among patients with PCOS aged 20-40 years undergoing their first IVF cycles with the GnRH-ant protocol, age was not a significant predictor of the initial FSH dosage. We developed a nomogram based on BMI, basal FSH, basal luteinizing hormone (bLH), anti-Müllerian hormone (AMH), and antral follicle count (AFC) to calculate the ideal initial FSH dosage for patients with PCOS undergoing IVF/ICSI using the GnRH-ant protocol. In addition, low BMI and high bLH and AMH levels and AFC appear to be risk factors for OHSS.

Conclusions: We clearly demonstrated that the initial FSH dosage for patients with PCOS undergoing IVF/ICSI with the GnRH-ant protocol may be calculated on the basis of the woman's BMI and ovarian reserve markers. The nomogram will help guide clinicians in the selection of the most appropriate initial FSH dose in the future.

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References

Hoeger K, Dokras A, Piltonen T . Update on PCOS: Consequences, Challenges, and Guiding Treatment. J Clin Endocrinol Metab. 2020; 106(3):e1071-e1083. DOI: 10.1210/clinem/dgaa839. View

Joham A, Norman R, Stener-Victorin E, Legro R, Franks S, Moran L . Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022; 10(9):668-680. DOI: 10.1016/S2213-8587(22)00163-2. View

Escobar-Morreale H . Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018; 14(5):270-284. DOI: 10.1038/nrendo.2018.24. View

Mimouni N, Paiva I, Barbotin A, Timzoura F, Plassard D, Le Gras S . Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process. Cell Metab. 2021; 33(3):513-530.e8. PMC: 7928942. DOI: 10.1016/j.cmet.2021.01.004. View

Fernandez R, Moore V, Rumbold A, Whitrow M, Avery J, Davies M . Diagnosis delayed: health profile differences between women with undiagnosed polycystic ovary syndrome and those with a clinical diagnosis by age 35 years. Hum Reprod. 2021; 36(8):2275-2284. PMC: 8289294. DOI: 10.1093/humrep/deab101. View

Deswal R, Nanda S, Dang A . Single nucleotide polymorphisms in treatment of polycystic ovary syndrome: a systematic review. Drug Metab Rev. 2019; 51(4):612-622. DOI: 10.1080/03602532.2019.1667380. View

Weiss N, Kostova E, Nahuis M, Mol B, van der Veen F, van Wely M . Gonadotrophins for ovulation induction in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2019; 1:CD010290. PMC: 6353048. DOI: 10.1002/14651858.CD010290.pub3. View

Balen A, Morley L, Misso M, Franks S, Legro R, Wijeyaratne C . The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016; 22(6):687-708. DOI: 10.1093/humupd/dmw025. View

Al-Inany H, Youssef M, Ayeleke R, Brown J, Lam W, Broekmans F . Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016; 4:CD001750. PMC: 8626739. DOI: 10.1002/14651858.CD001750.pub4. View

10.

Sunkara S, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A . Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011; 26(7):1768-74. DOI: 10.1093/humrep/der106. View

11.

Steward R, Lan L, Shah A, Yeh J, Price T, Goldfarb J . Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril. 2014; 101(4):967-73. DOI: 10.1016/j.fertnstert.2013.12.026. View

12.

Ji J, Liu Y, Tong X, Luo L, Ma J, Chen Z . The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod. 2013; 28(10):2728-34. DOI: 10.1093/humrep/det303. View

13.

Law Y, Zhang N, Kolibianakis E, Costello M, Keller E, Chambers G . Is there an optimal number of oocytes retrieved at which live birth rates or cumulative live birth rates per aspiration are maximized after ART? A systematic review. Reprod Biomed Online. 2021; 42(1):83-104. DOI: 10.1016/j.rbmo.2020.10.008. View

14.

Fleming R, Seifer D, Frattarelli J, Ruman J . Assessing ovarian response: antral follicle count versus anti-Müllerian hormone. Reprod Biomed Online. 2015; 31(4):486-96. DOI: 10.1016/j.rbmo.2015.06.015. View

15.

La Marca A, Sunkara S . Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update. 2013; 20(1):124-40. DOI: 10.1093/humupd/dmt037. View

16.

Iliodromiti S, Nelson S . Ovarian response biomarkers: physiology and performance. Curr Opin Obstet Gynecol. 2015; 27(3):182-6. DOI: 10.1097/GCO.0000000000000175. View

17.

Li R, Gong F, Zhu Y, Fang W, Yang J, Liu J . Anti-Müllerian hormone for prediction of ovarian response in Chinese infertile women undergoing IVF/ICSI cycles: a prospective, multi-centre, observational study. Reprod Biomed Online. 2016; 33(4):506-512. DOI: 10.1016/j.rbmo.2016.07.003. View

18.

Alviggi C, Humaidan P, Ezcurra D . Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols. Reprod Biol Endocrinol. 2012; 10:9. PMC: 3299595. DOI: 10.1186/1477-7827-10-9. View

19.

Abbara A, Patel A, Hunjan T, Clarke S, Chia G, Eng P . FSH Requirements for Follicle Growth During Controlled Ovarian Stimulation. Front Endocrinol (Lausanne). 2019; 10:579. PMC: 6718557. DOI: 10.3389/fendo.2019.00579. View

20.

Tal R, Seifer D . Ovarian reserve testing: a user's guide. Am J Obstet Gynecol. 2017; 217(2):129-140. DOI: 10.1016/j.ajog.2017.02.027. View