Exogenous Progesterone Rescue in Patients with Low Mid-luteal Serum Progesterone Levels Undergoing True Natural Vitrified-warmed Blastocyst Transfer

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2024 Nov 11

PMID 39527238

Authors

Murat Erden

Sezcan Mumusoglu

Irem Yarali Ozbek

Onur Ince

Sandro C Esteves

Peter Humaidan

Hakan Yarali

Affiliations

Soon will be listed here.

Abstract

Purpose: To explore whether a 25 mg subcutaneous progesterone daily rescue daily improves the reproductive outcomes in patients with low serum progesterone (P) levels (7-10 ng/mL), measured one day before true natural cycle (t-NC) frozen embryo transfer (FET).

Methods: A cohort study of 192 women undergoing t-NC warmed blastocyst transfer. Patients were stratified into three different groups based on serum P levels on the FET-1 day: patients who had serum P levels of 7-10 ng/mL and underwent rescue progesterone administration (rescue group), patients with serum P levels of 7-10 ng/mL without progesterone administration (non-rescue group), and patients with serum P > 10 ng/mL on FET-1 day (control group). The primary outcome was possible differences in live birth rate (LBR) between groups.

Results: The LBRs for the serum P 7-10 ng/mL without rescue, 7-10 ng/mL with rescue, and > 10 ng/mL (control) groups were 41%, 46%, and 52%, respectively (p = 0.61). The estimated adjusted probability of live birth for serum P 7-10 ng/mL without rescue, 7-10 ng/mL with rescue, and > 10 ng/mL (control) groups were also comparable: 43.5% (95% CI, 20.0-70.4%), 49.8% (95% CI, 28.1-71.6%), and 57.4% (95% CI, 44.0-69.8%), respectively.

Conclusion: Serum P levels higher than 7 ng/mL seem to secure LBRs in patients undergoing t-NC FET. A rescue policy consisting of a daily subcutaneous 25 mg progesterone dose in patients with serum P levels 7-10 ng/mL does not further enhance LBRs when compared to those patients with similar serum P levels without rescue.

References

De Geyter C, Wyns C, Calhaz-Jorge C, de Mouzon J, Ferraretti A, Kupka M . 20 years of the European IVF-monitoring Consortium registry: what have we learned? A comparison with registries from two other regions. Hum Reprod. 2020; 35(12):2832-2849. PMC: 7744162. DOI: 10.1093/humrep/deaa250. View

Roque M, Haahr T, Geber S, Esteves S, Humaidan P . Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update. 2018; 25(1):2-14. DOI: 10.1093/humupd/dmy033. View

Mumusoglu S, Polat M, Ozbek I, Bozdag G, Papanikolaou E, Esteves S . Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review. Front Endocrinol (Lausanne). 2021; 12:688237. PMC: 8299049. DOI: 10.3389/fendo.2021.688237. View

Busnelli A, Schirripa I, Fedele F, Bulfoni A, Levi-Setti P . Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis. Hum Reprod. 2022; 37(7):1619-1641. DOI: 10.1093/humrep/deac073. View

Roque M, Bedoschi G, Cecchino G, Esteves S . Fresh versus frozen blastocyst transfer. Lancet. 2019; 394(10205):1227-1228. DOI: 10.1016/S0140-6736(19)31393-5. View

Lawrenz B, Coughlan C, Melado L, Fatemi H . The ART of frozen embryo transfer: back to nature!. Gynecol Endocrinol. 2020; 36(6):479-483. DOI: 10.1080/09513590.2020.1740918. View

Hull M, Savage P, Bromham D, Ismail A, Morris A . The value of a single serum progesterone measurement in the midluteal phase as a criterion of a potentially fertile cycle ("ovulation") derived form treated and untreated conception cycles. Fertil Steril. 1982; 37(3):355-60. DOI: 10.1016/s0015-0282(16)46095-4. View

Jordan J, Craig K, Clifton D, Soules M . Luteal phase defect: the sensitivity and specificity of diagnostic methods in common clinical use. Fertil Steril. 1994; 62(1):54-62. DOI: 10.1016/s0015-0282(16)56815-0. View

ROSENBERG S, Luciano A, Riddick D . The luteal phase defect: the relative frequency of, and encouraging response to, treatment with vaginal progesterone. Fertil Steril. 1980; 34(1):17-20. DOI: 10.1016/s0015-0282(16)44831-4. View

10.

Gaggiotti-Marre S, Alvarez M, Gonzalez-Foruria I, Parriego M, Garcia S, Martinez F . Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates. Hum Reprod. 2020; 35(7):1623-1629. DOI: 10.1093/humrep/deaa092. View

11.

Noble M, Child T . A UK-wide cross-sectional survey of practice exploring current trends in endometrial preparation for frozen-thawed embryo replacement. Hum Fertil (Camb). 2020; 25(2):283-290. DOI: 10.1080/14647273.2020.1786171. View

12.

Wetzels L, Hoogland H . Relation between ultrasonographic evidence of ovulation and hormonal parameters: luteinizing hormone surge and initial progesterone rise. Fertil Steril. 1982; 37(3):336-41. DOI: 10.1016/s0015-0282(16)46092-9. View

13.

Erden M, Mumusoglu S, Polat M, Ozbek I, Esteves S, Humaidan P . The LH surge and ovulation re-visited: a systematic review and meta-analysis and implications for true natural cycle frozen thawed embryo transfer. Hum Reprod Update. 2022; 28(5):717-732. DOI: 10.1093/humupd/dmac012. View

14.

Wu H, Zhou P, Lin X, Wang S, Zhang S . Endometrial preparation for frozen-thawed embryo transfer cycles: a systematic review and network meta-analysis. J Assist Reprod Genet. 2021; 38(8):1913-1926. PMC: 8417182. DOI: 10.1007/s10815-021-02125-0. View

14.

Erden M, Polat M, Mumusoglu S, Ozbek I, Dere G, Karakoc Sokmensuer L . Vitrified-warmed blastocyst transfer timing related to LH surge in true natural cycle and its impact on ongoing pregnancy rates. Reprod Biomed Online. 2022; 45(3):440-447. DOI: 10.1016/j.rbmo.2022.04.018. View

15.

Irani M, Robles A, Gunnala V, Reichman D, Rosenwaks Z . Optimal parameters for determining the LH surge in natural cycle frozen-thawed embryo transfers. J Ovarian Res. 2017; 10(1):70. PMC: 5644145. DOI: 10.1186/s13048-017-0367-7. View

16.

Mumusoglu S, Yarali I, Bozdag G, Ozdemir P, Polat M, Karakoc Sokmensuer L . Time-lapse morphokinetic assessment has low to moderate ability to predict euploidy when patient- and ovarian stimulation-related factors are taken into account with the use of clustered data analysis. Fertil Steril. 2016; 107(2):413-421.e4. DOI: 10.1016/j.fertnstert.2016.11.005. View

17.

Gardner D, Schoolcraft W . Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999; 11(3):307-11. DOI: 10.1097/00001703-199906000-00013. View

18.

Melo P, Chung Y, Pickering O, Price M, Fishel S, Khairy M . Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis. Fertil Steril. 2021; 116(6):1534-1556. DOI: 10.1016/j.fertnstert.2021.07.002. View

19.

Mumusoglu S, Erden M, Ozbek I, Ince O, Esteves S, Humaidan P . The true natural cycle frozen embryo transfer - impact of patient and follicular phase characteristics on serum progesterone levels one day prior to warmed blastocyst transfer. Reprod Biol Endocrinol. 2023; 21(1):86. PMC: 10506193. DOI: 10.1186/s12958-023-01136-z. View