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Effect of metformin and exenatide on pregnancy rate and pregnancy outcomes in overweight or obese infertility PCOS women: long-term follow-up of an RCT

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The majority of Polycystic ovary syndrome (PCOS) are overweight or obese with increased infertility and high risk of pregnancy complications. We aim to compare efficacy of metformin and exenatide on spontaneous pregnancy rate, overall pregnancy rate after assisted reproductive technology treatment (ART) and pregnancy outcomes in overweight or obese infertility PCOS.

Methods

In this long-term follow-up study, 160 overweight or obese infertility Chinese PCOS were randomized to exenatide or metformin treatment for 12 weeks. Afterward, all were treated with metformin alone until pregnancy confirmed and followed until delivery. If patients failed spontaneous pregnancy during the second 12 weeks, ART could be offered until end of 64 weeks. The primary outcome was spontaneous pregnancy rate.

Results

At week 24, 29.2% of women in exenatide group conceived spontaneously while 14.7% in metformin group (p = 0.03). At week 64, total pregnancy rates were 79.2% in exenatide group and 76% in metformin group without significant difference (p = 0.65). Between two groups, there was no significant difference of pregnancy outcomes (p > 0.05). A stepwise logistic regression showed that spontaneous pregnancy was positively associated with body weight reduction and HOMA-IR improvement in either group.

Conclusion

In overweight or obese infertility Chinese PCOS, 12 weeks pregestational exenatide treatment resulted in more spontaneous pregnancy likely due to greater weight reduction and improvement of insulin resistance compared with metformin treatment without obvious benefit on overall pregnancy rate after ART or pregnancy outcomes of successful conceived women.

Trial registration

This clinical trial was registered at Chinese Clinical Trials Registry (ChiCTR-IIR-16008084) on 13/3/2016.

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Abbreviations

AG:

Abdominal girth

AMH:

Anti-Mullerian hormone

ART:

Assisted reproductive technology treatment

BMI:

Body mass index

CAH:

Congenital adrenal hyperplasia

DM:

Diabetes mellitus

EXE:

Exenatide treatment

FPG:

Fasting plasma glucose

Fins:

Fasting insulin

HDL-c:

High density lipopretein cholesterol

HPO:

Hypothalamic-pituitary-ovarian

HOMA-β:

Homeostasis model assessment of b-cell function

HOMA-IR:

Homoeostasis model assessment of insulin resistance

2hPPG:

2 Hours postprandial plasma glucose

2hIns:

2 Hours postglucose load insulin

GLP-1RA:

Glucagon-like peptide-1 receptor agonist

GDM:

Gestational diabetes

GI:

Gastrointestinal

IVF-ET:

In-vitro fertilization and embryo transfer

IADPSG:

International Association of Diabetes and Pregnancy Study Groups

ITT:

Intention-to-treat

LDL-c:

Low density lipoprotein cholesterol

MET:

Metformin treatment

OGTT:

Oral glucose tolerant test

OCP:

Oral contraceptive pill

PP:

Per-protocol

PCOS:

Polycystic ovary syndrome

T2DM:

Type 2 diabetes mellitus

TG:

Total triglyceride

TC:

Total cholesterol

SAS:

Statistics Analysis System

SD:

Standard deviation

WHR:

Waist-hip rate

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Acknowledgements

The authors thank the staff at the Endocrinology and Metabolism Department and the Gynaecology & Obstetrics Department, the Third Affiliated Hospital of Guangzhou Medical University for assistance with study execution and data collection. In particular, we want to thank the patients for their participation in this trial.

Funding

This study was supported by National Natural Science Foundation of China (No. 81200607) and Initial Funds of The Third Affiliated Hospital of Guangzhou Medical University (No. 2017B11).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China

    Renyuan Li, Tingting Mai, Siyuan Zheng & Ying Zhang

  2. Key Laboratory for Major Obstetric Diseases of Guangdong Higher Education Institutes, Guangzhou, Guangdong, People’s Republic of China

    Renyuan Li, Tingting Mai, Siyuan Zheng & Ying Zhang

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  1. Renyuan Li
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Contributions

SZ and TM contributed to the preliminary study design, data collection and statistical analysis. RL was involved in the integrity and interpretation of the data, and manuscript writing. And YZ is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for finial study design and quality control of clinical trial. All the authors approved the final version of the manuscript.

Corresponding author

Correspondence to Ying Zhang.

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Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethical approval

All the procedures performed in this clinical trial 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. On January 8th, 2016, the study was approved by the Medical Ethics Committee of The Third Affiliated Hospital of Guangzhou Medical University (Approved ethic committee number: 002/2016). The study was registered at Chinese Clinical Trials Registry (ChiCTR-IIR-16008084) on 13/3/2016. The long-term follow-up procedures of this clinical trial was reapproved by the Medical Ethics Committee of The Third Affiliated Hospital of Guangzhou Medical University (Approved ethic committee number: 061/2018) on July 18th, 2018. The study was reregistered at Chinese Clinical Trials Registry (ChiCTR1900020516).

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Informed consent was obtained from all individual participants included in the study.

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Li, R., Mai, T., Zheng, S. et al. Effect of metformin and exenatide on pregnancy rate and pregnancy outcomes in overweight or obese infertility PCOS women: long-term follow-up of an RCT. Arch Gynecol Obstet 306, 1711–1721 (2022). https://doi.org/10.1007/s00404-022-06700-3

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