Low dosing of gonadotropins in in vitro fertilization cycles for women with poor ovarian reserve: systematic review and meta-analysis

Low doses of gonadotropins alone or combined with oral compounds and high doses of gonadotropins have comparable pregnancy rates in women with poor ovarian reserve undergoing in vitro fertilization/intracytoplasmic sperm injection.

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Volume 109, Issue 2, Pages 289–301

Authors:

Mohamed Abdel-Fattah Youssef, Ph.D., Madelon van Wely, Ph.D., Monique Mochtar, Ph.D., Usama Mohamed Fouda, M.D., Ashraf Eldaly, M.D., Eman Zein El Abidin, M.D., Ahmed Elhalwagy, M.D., Ahmed Abdel Mageed Abdallah, M.D., Sherif Sameh Zaki, M.D., Mohamed Sayed Abdel Ghafar, M.D., Mohamed Nagi Mohesen, M.D., Fulco van der Veen, Ph.D.

Abstract:

Objective

To evaluate the effectiveness of low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens in terms of ongoing pregnancy per fresh IVF attempt in women with poor ovarian reserve undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment.

Design

A systematic review and meta-analysis of randomized controlled studies that evaluate the effectiveness of low dosing of gonadotropins alone or combined with oral compounds compared with high doses of gonadotropins in women with poor ovarian reserve undergoing IVF/ICSI treatment.

Setting

Not applicable.

Patient(s)

Subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment.

Intervention(s)

We searched the PubMed, EMBASE, Web of Science, the Cochrane Library, and the Clinical Trials Registry using medical subject headings and free text terms up to June 2016, without language or year restrictions. We included randomized controlled studies (RCTs) enrolling subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment and comparing low doses of gonadotropins and gonadotropins combined with oral compounds versus high doses of gonadotropins. We assessed the risk of bias using the criteria recommended by the Cochrane Collaboration. We pooled the results by meta-analysis using the fixed and random effects model.

Main Outcomes Measure(s)

The primary outcome was ongoing pregnancy rate (PR) per woman randomized.

Result(s)

We retrieved 787 records. Fourteen RCTs (N = 2,104 women) were included in the analysis. Five studies (N = 717 women) compared low doses of gonadotropins versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (2 RCTs: risk rate 0.98, 95% confidence interval 0.62–1.57, I2 = 0). Nine studies (N = 1,387 women) compared ovarian stimulation using gonadotropins combined with the oral compounds letrozole (n = 6) or clomiphene citrate (CC) (n = 3) versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (3 RCTs: risk rate 0.90, 95% confidence interval 0.63–1.27, I2 = 0).

Conclusion(s)

We found no evidence of a difference in pregnancy outcomes between low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens. Whether low doses of gonadotropins or gonadotropins combined with oral compounds is to be preferred is unknown, as they have never been compared head to head. A health economic analysis to test the hypothesis that an ovarian stimulation with low dosing is more cost-effective than high doses of gonadotropins is needed.

Prospero Registration Number

CRD42016041301.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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