Effectiveness of progesterone supplementation in women presenting low progesterone levels on the day of frozen embryo transfer: a randomised controlled trial

Thi Minh Chau Le, Khue Tu Duong, Quoc Anh Nguyen, Phuc Thinh Ong, Thi Hong Nhung Nguyen, Thi Cam Thu Thai, Quang Thanh Le, Matheus Roque, Carlo Alviggi, Thi Minh Chau Le, Khue Tu Duong, Quoc Anh Nguyen, Phuc Thinh Ong, Thi Hong Nhung Nguyen, Thi Cam Thu Thai, Quang Thanh Le, Matheus Roque, Carlo Alviggi

Abstract

Introduction: Progesterone is an essential hormone involved in the process of implantation and pregnancy maintenance. Evidence from recent studies has supported the importance of serum progesterone level around the time of embryo transfer in hormonal replacement therapy frozen embryo transfer cycles and recommended the need for individualised luteal support. Low progesterone around the time of embryo transfer is found to be associated with decreased rate of pregnancy after frozen embryo transfer. This single-centre, longitudinal, randomised, interventional controlled study aims to compare the rate of ongoing pregnancy between two groups of women with progesterone level below 10 ng/mL on the day of frozen embryo transfer: the study group using 800 mg vaginal micronised progesterone supplemented with 50 mg intramuscular progesterone per day and the control group using only 800 mg vaginal micronised progesterone.

Methods and analysis: We enrol patients who are undergoing frozen embryo transfers with blastocyst-stage or cleavage-stage embryos and who satisfy the inclusion and exclusion criteria. After signing the informed consent, participants are randomised into two groups: the study group using vaginal micronised progesterone supplemented with progesterone intramuscular 50 mg per day and the control group using only vaginal micronised progesterone. Randomisation will be performed using R software at a 1:1 allocation ratio. Sequentially numbered, opaque sealed envelopes are used for allocation. The primary outcome is the rate of ongoing pregnancy. To demonstrate a difference of 10% with regard to rate of ongoing pregnancy, at least 370 participants per arm are required (type I error α=0.05, power=0.8). Assuming a dropout rate of 10%, a total of 824 patients (412 per group) will be invited.

Ethics and dissemination: This study was approved by the Ethics Committee of Tu Du Hospital on 17 May 2021 (reference number: 1251/QĐ-BVTD). All participants provide informed consent before being enrolled in the study. The results of our study will be submitted to reproductive medicine conferences and journals.

Trial registration number: NCT04897269.

Keywords: gynaecology; reproductive medicine; subfertility.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flow chart of recruitment. FET, frozen-thawed embryo transfer. (P4 - progesterone)

References

    1. Di Renzo GC, Giardina I, Clerici G, et al. . Progesterone in normal and pathological pregnancy. Horm Mol Biol Clin Investig 2016;27:35–48. 10.1515/hmbci-2016-0038
    1. Csapo AI, Pulkkinen MO, Kaihola HL. The relationship between the timing of luteectomy and the incidence of complete abortions. Am J Obstet Gynecol 1974;118:985–9. 10.1016/0002-9378(74)90671-1
    1. Orazov MR, Radzinskiy VE, Nosenko EN, et al. . Combination therapeutic options in the treatment of the luteal phase deficiency. Gynecol Endocrinol 2017;33:1–4. 10.1080/09513590.2017.1399695
    1. Practice Committee of the American Society for Reproductive Medicine . Current clinical irrelevance of luteal phase deficiency: a Committee opinion. Fertil Steril 2015;103:e27–32. 10.1016/j.fertnstert.2014.12.128
    1. Jordan J, Craig K, Clifton DK, et al. . Luteal phase defect: the sensitivity and specificity of diagnostic methods in common clinical use. Fertil Steril 1994;62:54–62. 10.1016/s0015-0282(16)56815-0
    1. Evans J, Hannan NJ, Edgell TA, et al. . Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence. Hum Reprod Update 2014;20:808–21. 10.1093/humupd/dmu027
    1. Mackens S, Santos-Ribeiro S, van de Vijver A, et al. . Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum Reprod 2017;32:2234–42. 10.1093/humrep/dex285
    1. Commissaire M, Cédrin-Durnerin I, Peigné M. [Progesterone and frozen-thawed embryo transfer after hormonal replacement therapy for endometrial preparation: An update on medical practices]. Gynecol Obstet Fertil Senol 2020;48:196–203. 10.1016/j.gofs.2019.11.003
    1. Pan Y, Li B, Wang Z, et al. . Hormone replacement versus natural cycle protocols of endometrial preparation for frozen embryo transfer. Front Endocrinol 2020;11:546532. 10.3389/fendo.2020.546532
    1. Cédrin-Durnerin I, Isnard T, Mahdjoub S, et al. . Serum progesterone concentration and live birth rate in frozen-thawed embryo transfers with hormonally prepared endometrium. Reprod Biomed Online 2019;38:472–80. 10.1016/j.rbmo.2018.11.026
    1. Labarta E, Mariani G, Holtmann N, et al. . Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod 2017;32:2437–42. 10.1093/humrep/dex316
    1. Gaggiotti-Marre S, Martinez F, Coll L, et al. . Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates. Gynecol Endocrinol 2019;35:439–42. 10.1080/09513590.2018.1534952
    1. Yarali H, Polat M, Mumusoglu S, et al. . Subcutaneous luteal phase progesterone rescue rectifies ongoing pregnancy rates in hormone replacement therapy vitrified-warmed blastocyst transfer cycles. Reprod Biomed Online 2021;43:45–51. 10.1016/j.rbmo.2021.04.011
    1. Álvarez M, Gaggiotti-Marre S, Martínez F, et al. . Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study. Hum Reprod 2021;36:1552–60. 10.1093/humrep/deab031
    1. De Ziegler D, Bulletti C, De Monstier B, et al. . The first uterine pass effect. Ann N Y Acad Sci 1997;828:291–9. 10.1111/j.1749-6632.1997.tb48550.x
    1. Zegers-Hochschild F, Schwarze J-E, Borrero C. Delivery routes of progesterone in assisted reproduction. Expert Rev Obstet Gynecol 2006;1:173–82. 10.1586/17474108.1.2.173
    1. WHO Expert Consultation . Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. The Lancet 2004;363:157–63. 10.1016/S0140-6736(03)15268-3
    1. Zegers-Hochschild F, Adamson GD, Dyer S, et al. . The International glossary on infertility and fertility care, 2017. Fertil Steril 2017;108:393–406. 10.1016/j.fertnstert.2017.06.005

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