Less is More: Increased Gonadotropin Use for Ovarian Stimulation Adversely Influences Clinical Pregnancy and Live Birth After in Vitro Fertilization

Overview

Journal Fertil Steril

Specialty Reproductive Medicine

Date 2008 Apr 29

PMID 18440515

Citations 28

Authors

Lubna Pal

Sangita Jindal

Barry R Witt

Nanette Santoro

Affiliations

Soon will be listed here.

Abstract

Objective: To determine if attempts to maximize oocyte yield during ovarian stimulation translates into improved outcome of in vitro fertilization (IVF) cycles.

Design: Retrospective study.

Setting: Academic tertiary care IVF center.

Patient(s): 806 de-identified nondonor IVF cycles.

Intervention(s): Evaluation of fresh nondonor IVF cycles (n = 806) for the period January 1, 1999, to December 30, 2001.

Main Outcome Measure(s): Cycle cancellation, clinical pregnancy, spontaneous miscarriage, and live birth after IVF.

Result(s): Advancing age, independent of ovarian reserve status (reflected by early follicular phase FSH and estradiol) augured a worse prognosis for all outcomes. Higher gonadotropin use lowered cycle cancellations but was associated with a statistically significantly reduced likelihood of clinical pregnancy and live birth and a trend toward a higher likelihood for spontaneous miscarriage after IVF.

Conclusion(s): Our data add to the accruing literature suggesting adverse influences of excess gonadotropin use on IVF outcomes. Although an aggressive approach to controlled ovarian hyperstimulation results in a statistically significant reduction in cycle cancellations, the excessive use of gonadotropins detrimentally influences live birth after IVF.

Citing Articles

Unraveling the Clinical FSH Conundrum: Insights From the Small Ovarian Reserve Heifer Model.

Ireland J, Karl K, Latham K Mol Reprod Dev. 2025; 92(2):e70007.

PMID: 39935023 PMC: 11814505. DOI: 10.1002/mrd.70007.

Embryo production by Holstein heifers superovulated with a recombinant long-acting follicle-stimulating hormone analog.

Mirzaei A, Londono-Mendez M, Lasso-Ramirez S, Adams P, Seekford Z, Bromfield J J Anim Sci. 2024; 102.

PMID: 39447034 PMC: 11582645. DOI: 10.1093/jas/skae326.

Optimizing oocyte yield utilizing a machine learning model for dose and trigger decisions, a multi-center, prospective study.

Canon C, Leibner L, Fanton M, Chang Z, Suraj V, Lee J Sci Rep. 2024; 14(1):18721.

PMID: 39164339 PMC: 11335759. DOI: 10.1038/s41598-024-69165-1.

A Dose-Response Study on Functional and Transcriptomic Effects of FSH on Ex Vivo Mouse Folliculogenesis.

Zhan T, Zhang J, Zhang Y, Zhao Q, Chemerinski A, Douglas N Endocrinology. 2024; 165(7).

PMID: 38735763 PMC: 11129714. DOI: 10.1210/endocr/bqae054.

Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer: A Secondary Analysis of a Randomized Clinical Trial.

Ni T, Zhou W, Liu Y, Cui W, Liu Y, Lu J JAMA Netw Open. 2024; 7(4):e244438.

PMID: 38564220 PMC: 10988349. DOI: 10.1001/jamanetworkopen.2024.4438.

References

Toner J, Philput C, Jones G, Muasher S . Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age. Fertil Steril. 1991; 55(4):784-91. DOI: 10.1016/s0015-0282(16)54249-6. View

Freeman S, Yang Q, Allran K, Taft L, Sherman S . Women with a reduced ovarian complement may have an increased risk for a child with Down syndrome. Am J Hum Genet. 2000; 66(5):1680-3. PMC: 1378004. DOI: 10.1086/302907. View

Chuang C, Chen C, Chao K, Chen S, Ho H, Yang Y . Age is a better predictor of pregnancy potential than basal follicle-stimulating hormone levels in women undergoing in vitro fertilization. Fertil Steril. 2003; 79(1):63-8. DOI: 10.1016/s0015-0282(02)04562-4. View

Gurbuz B, Yalti S, Ozden S, Ficicioglu C . High basal estradiol level and FSH/LH ratio in unexplained recurrent pregnancy loss. Arch Gynecol Obstet. 2003; 270(1):37-9. DOI: 10.1007/s00404-003-0490-0. View

Hock D, Louie H, Shelden R, Ananth C, Kemmann E . The need to step up the gonadotropin dosage in the stimulation phase of IVF treatment predicts a poor outcome. J Assist Reprod Genet. 1998; 15(7):427-30. PMC: 3454803. DOI: 10.1007/BF02744936. View

Ertzeid G, Storeng R . Adverse effects of gonadotrophin treatment on pre- and postimplantation development in mice. J Reprod Fertil. 1992; 96(2):649-55. DOI: 10.1530/jrf.0.0960649. View

Abdalla H, Thum M . An elevated basal FSH reflects a quantitative rather than qualitative decline of the ovarian reserve. Hum Reprod. 2004; 19(4):893-8. DOI: 10.1093/humrep/deh141. View

Scott R, Opsahl M, Leonardi M, Neall G, Illions E, Navot D . Life table analysis of pregnancy rates in a general infertility population relative to ovarian reserve and patient age. Hum Reprod. 1995; 10(7):1706-10. DOI: 10.1093/oxfordjournals.humrep.a136159. View

Kaleli S, Yanikkaya-Demirel G, Erel C, Senturk L, Topcuoglu A, Irez T . High rate of aneuploidy in luteinized granulosa cells obtained from follicular fluid in women who underwent controlled ovarian hyperstimulation. Fertil Steril. 2005; 84(3):802-4. DOI: 10.1016/j.fertnstert.2005.02.040. View

10.

Miller B, Armstrong D . Superovulatory doses of pregnant mare serum gonadotropin cause delayed implantation and infertility in immature rats. Biol Reprod. 1981; 25(2):253-60. DOI: 10.1095/biolreprod25.2.253. View

11.

Levi A, Raynault M, Bergh P, Drews M, Miller B, Scott Jr R . Reproductive outcome in patients with diminished ovarian reserve. Fertil Steril. 2001; 76(4):666-9. DOI: 10.1016/s0015-0282(01)02017-9. View

12.

Tan S, Child T, Cheung A, Fluker M, Yuzpe A, Casper R . A randomized, double-blind, multicenter study comparing a starting dose of 100 IU or 200 IU of recombinant follicle stimulating hormone (Puregon) in women undergoing controlled ovarian hyperstimulation for IVF treatment. J Assist Reprod Genet. 2005; 22(2):81-8. PMC: 3455475. DOI: 10.1007/s10815-005-1497-1. View

13.

Nasseri A, Mukherjee T, Grifo J, Noyes N, Krey L, Copperman A . Elevated day 3 serum follicle stimulating hormone and/or estradiol may predict fetal aneuploidy. Fertil Steril. 1999; 71(4):715-8. DOI: 10.1016/s0015-0282(98)00525-1. View

14.

Warburton D . Biological aging and the etiology of aneuploidy. Cytogenet Genome Res. 2005; 111(3-4):266-72. DOI: 10.1159/000086899. View

15.

Check J, Peymer M, Lurie D . Effect of age on pregnancy outcome without assisted reproductive technology in women with elevated early follicular phase serum follicle-stimulating hormone levels. Gynecol Obstet Invest. 1998; 45(4):217-20. DOI: 10.1159/000009970. View

16.

Sibug R, Helmerhorst F, Tijssen A, de Kloet E, de Koning J . Gonadotrophin stimulation reduces VEGF(120) expression in the mouse uterus during the peri-implantation period. Hum Reprod. 2002; 17(6):1643-8. DOI: 10.1093/humrep/17.6.1643. View

17.

Faddy M, Gosden R . A model conforming the decline in follicle numbers to the age of menopause in women. Hum Reprod. 1996; 11(7):1484-6. DOI: 10.1093/oxfordjournals.humrep.a019422. View

18.

Hanoch J, Lavy Y, Holzer H, Hurwitz A, Simon A, Revel A . Young low responders protected from untoward effects of reduced ovarian response. Fertil Steril. 1998; 69(6):1001-4. DOI: 10.1016/s0015-0282(98)00079-x. View

19.

van Hooff M, Alberda A, Huisman G, ZEILMAKER G, Leerentveld R . Doubling the human menopausal gonadotrophin dose in the course of an in-vitro fertilization treatment cycle in low responders: a randomized study. Hum Reprod. 1993; 8(3):369-73. DOI: 10.1093/oxfordjournals.humrep.a138053. View

20.

El-Toukhy T, Khalaf Y, Hart R, Taylor A, Braude P . Young age does not protect against the adverse effects of reduced ovarian reserve--an eight year study. Hum Reprod. 2002; 17(6):1519-24. DOI: 10.1093/humrep/17.6.1519. View