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. 2023 Apr;307(4):1073-1081.
doi: 10.1007/s00404-022-06878-6. Epub 2022 Dec 16.

Low-dose clomiphene citrate does not reduce implantation and live birth rates in otherwise unstimulated modified natural cycle IVF-retrospective cohort study

Flavia Grädel  1   2 , Michael von Wolff  1 , Alexandra Sabrina Kohl Schwartz  1   3 , Vera Ruth Mitter  4
Affiliations

Low-dose clomiphene citrate does not reduce implantation and live birth rates in otherwise unstimulated modified natural cycle IVF-retrospective cohort study

Flavia Grädel et al. Arch Gynecol Obstet. 2023 Apr.

Abstract

Research question: Does antioestrogen effect of clomiphene citrate (CC) on the endometrium reduce implantation and thereby decrease pregnancy and live birth rate per transferred embryo?

Methods: In this cohort, unstimulated IVF cycles modified with clomiphene citrate (CC-NC-IVF) and unstimulated, natural IVF cycles (NC-IVF) conducted between 2011 and 2016 were included. CC was applied in a dosage of 25mcg per day, starting on cycle day 7 until ovulation trigger day. Primary outcomes were clinical pregnancy rate, defined as amniotic sac visible in ultrasound, and live birth rate per transferred embryo. Miscarriage rate calculated as amniotic sac not ending in a live birth was secondary outcome. A modified mixed-effect Poisson regression model was applied, and adjustments were made for female age, parity, type and cause of infertility. Additionally, stratification by parity and age was performed.

Results: Four hundred and ninety-nine couples underwent a total of 1042 IVF cycles, 453 being NC-IVF and 589 being CC-NC-IVF cycles. Baseline characteristics of both groups did not differ. Addition of CC did neither decrease clinical pregnancy rate (aRR 0.86; 95% CI 0.67-1.12) nor live birth rate per transferred embryo (aRR 0.84; 95% CI 0.62-1.13) in comparison with NC-IVF. Miscarriage rate did not differ between CC-NC-IVF and NC-IVF (aRR 0.95; 95% CI 0.57-1.57).

Conclusion: Low-dose CC does not reduce pregnancy or live birth rate per transferred embryo. It can be used in infertility treatment without negatively affecting the endometrium and implantation.

Keywords: Bern IVF Cohort; Clinical pregnancy; Endometrium; FIVNAT; Modified natural-cycle; Pregnancy rate.

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Conflict of interest statement

Flavia Grädel has no financial or non-financial interests to declare. Michael von Wolff received a research grant from IBSA Institut Biochimique, Lugano, Switzerland. Alexandra S Kohl Schwartz has received funding for the set-up of the Bern IVF cohort from Merck, Switzerland SA. Vera R Mitter received congress and travel support from Theramex.

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Fig. 1
Data sources and creation of study population
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References

    1. Kerin JF, Liu JH, Phillipou G, Yen SSC. Evidence for a hypothalamic site of action of clomiphene citrate in women. J Clin Endocrinol Metab. 1985 doi: 10.1210/jcem-61-2-265. - DOI - PubMed
    1. Rebar R, Judd HL, Yen SSC, et al. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest. 1976 doi: 10.1172/JCI108400. - DOI - PMC - PubMed
    1. Johnson MH, Elder K. The Oldham notebooks: an analysis of the development of IVF 1969–1978. IV. Ethical aspects. Reprod Biomed Soc Online. 2015 doi: 10.1016/j.rbms.2015.04.002. - DOI - PMC - PubMed
    1. Zarei A, Alborzi S, Askary E, et al. Effects of clomiphene citrate for prevention of premature luteinizing hormone surge in those undergoing intrauterine insemination outcome: a randomized, double-blind, placebo-controlled trial. J Adv Pharm Technol Res. 2018 doi: 10.4103/japtr.JAPTR_293_18. - DOI - PMC - PubMed
    1. Abe T, Yabuuchi A, Ezoe K, et al. Success rates in minimal stimulation cycle IVF with clomiphene citrate only. J Assist Reprod Genet. 2020;37:297–304. doi: 10.1007/s10815-019-01662-z. - DOI - PMC - PubMed

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