Assisted reproductive technology and uterine cancer risk. A systematic review and meta-analysis

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BACKGROUND: The problem of infertility has not only medical, but also socio-demographic significance. To date, the global scale of the spread of various forms of infertility is beyond doubt among specialists around the world. This, in turn, causes an increase in the frequency of prescribing assisted reproductive technologies, but the question of the relationship between the prescribing of drugs used to treat infertility and the risk of developing cancer of the uterine body remains poorly understood.

AIM: The aim of this study was to assess the possible relationship between in vitro fertilization, the use of ovulation stimulation drugs and the risk of developing uterine cancer in women with infertility.

MATERIALS AND METHODS: This literature systematic review is based on resources from the following databases: Medline, ClinicalKey, Google Scholar, Embase, the Cochrane Library, and eLIBRARY for the period 1999–2022. The search for publications was carried out using keywords defined in accordance with the PICO principle (P, population or patients; I, intervention; C, comparison; O, outcomes): “female”, “women”, “infertility”, “infertility treatment”, “in vitro fertilization”, “IVF”, “assisted reproductive technology”, “ART”, “ovarian stimulation”, “ovarian hyperstimulation”, “clomiphene citrate”, “hCG”, “hMG”, “tamoxifen”, “uterine”, “endometrial”, “cancer”, “carcinoma neoplasm”, “uterine neoplasm”. The following SQL operators were used during the search: AND and OR.

RESULTS: The search resulted in 37 representative publications, with eight studies selected for meta-analysis.

CONCLUSIONS: This systematic review and meta-analysis have demonstrated the ambiguity of the design and results of studies on the possible relationship of uterine cancer and assisted reproductive technology methods published to date. The issue under review is urgent due to the high frequency of infertility and an increase in the frequency of gynecologic cancers. The conducted studies confirm that it is impossible to evaluate the carcinogenic effect of ovulation inducers or in vitro fertilization methods without adjusting for the infertility factor, as well as risk factors for uterine cancer. There is still a high need for further research, particularly for studying the safety profile of infertility treatment methods in relation to long-term cancer risks.

作者简介

Lidia Klyukina

I.M. Sechenov First Moscow State Medical University

Email: lidiaklyukina@mail.ru
ORCID iD: 0000-0001-7602-4584
SPIN 代码: 1686-2663

MD

俄罗斯联邦, 3 Ivankovskoe Hwy., Moscow, 125367

Elena Sosnova

I.M. Sechenov First Moscow State Medical University

Email: sosnova-elena@inbox.ru
ORCID iD: 0000-0002-1732-6870
SPIN 代码: 6313-9959
Scopus 作者 ID: 6506060490
Researcher ID: P-9736-2017

MD, Dr. Sci. (Med.), Professor

俄罗斯联邦, 3 Ivankovskoe Hwy., Moscow, 125367

Anton Ishchenko

National Medical Research Center “Treatment and Rehabilitation Center”

编辑信件的主要联系方式.
Email: ra2001_2001@mail.ru
ORCID iD: 0000-0001-6673-3934
SPIN 代码: 2306-4571
Scopus 作者 ID: 57192960633

MD, Cand. Sci. (Med.)

俄罗斯联邦, 3 Ivankovskoe Hwy., Moscow, 125367

参考

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2. Fig. 1. Methodology for searching and selecting studies for meta-analysis

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3. Fig. 2. Tree diagram. Comparative analysis of the incidence of uterine cancer in the IVF group and the group without IVF in studies 1999–2022. ЭКО — IVF; без ЭКО — non-IVF; CI — confidence interval

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4. Fig. 3. Tree diagram. Comparative analysis of the standardized incidence rate (SIR) for uterine cancer in the IVF group in studies 1999–2022. SIR — standardized index of detection; SE — standard error; IV, Random, 95% CI — confidence interval

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5. Fig. 4. Tree diagram. Comparative analysis of hazard ratio (HR) indicators of endometrial cancer development in the IVF group in studies 1999–2022. SE — standard error; CI — confidence interval

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版权所有 © Klyukina L.A., Sosnova E.A., Ishchenko A.А., 2022

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