The clinical relevance of luteal phase progesterone support in true natural cycle cryopreserved blastocyst stage embryo transfers: a retrospective cohort study

Abstract

Background More than 67% of all embryos transferred in the United States involve frozen-thawed embryos. Progesterone supplementation is necessary in medicated cycles to luteinize the endometrium and prepare it for implantation, but little data is available to show if this is beneficial in true natural cycles. We evaluated the use of luteal phase progesterone supplementation for cryopreserved/warmed blastocyst transfers in true natural cycles not using an ovulatory trigger. Methods Retrospective cohort study in a single academic medical center. We studied the use of luteal phase progesterone supplementation in patients undergoing true natural cycle cryopreserved blastocyst embryo transfers. Our primary outcome measure was ongoing pregnancy rate, with other pregnancy outcomes being evaluated (i.e. implantation rate, miscarriage rate, ectopic rate, and multifetal gestation). Categorical data were analyzed utilizing Fisher’s exact test and all binary variables were analyzed using log-binomial regression to produce a risk ratio. Results Two hundred twenty-nine patients were included in the analysis with 149 receiving luteal phase progesterone supplementation and 80 receiving no luteal phase support. Patient demographic and cycle characteristics, and embryo quality were similar between the two groups. No difference was seen in ongoing pregnancy rate (49.0% vs. 47.5%, p = 0.8738), clinical pregnancy rate (50.3% vs. 47.5%, p = 0.7483), positive HCG rate (62.4% vs. 57.5%, p = 0.5965), miscarriage/abortion rate (5.4% vs. 2.5%, p = 0.2622), ectopic pregnancy rate (0% vs. 1.3%, p = 0.3493), or multifetal gestations (7.4% vs. 3.8%, p = 0.3166). Conclusion(s) The addition of luteal phase progesterone support in true natural cycle cryopreserved blastocyst embryo transfers did not improve pregnancy outcomes and therefore the routine use in practice cannot be recommended based on this study, but the utilization should not be discouraged without further studies. Capsule Progesterone supplementation as luteal phase support in true natural cycle cryopreserved blastocyst transfers does not improve ongoing pregnancies.

Impact of progesterone-free luteal phase support following natural cycle frozen embryo transfer: Study protocol for a multicenter, non-inferiority, randomized controlled trial

“…In 2013, a RCT with small sample size ( n = 102) conducted by Eftekhar et al comparing NC-FET with no LPS, LPS did not result in higher clinical pregnancy and implantation rates or lower miscarriage rates ( 9 ). Coincidentally, Waldman et al reported similar results in their retrospective study ( 10 ). Nevertheless, several recent studies showed that patients undergoing LPS with vaginal P 4 in NC-FET had higher LBR and lower miscarriage rates ( 11 – 13 ).…”

Finding of the optimal preparation and timing of endometrium in frozen-thawed embryo transfer: a literature review of clinical evidence

“…The application of luteal phase support (LPS) in true-NC FET remained to be elucidated. The available retrospective studies revealed that some studies suggested the application of LPS ( 41 ), whereas other studies showed comparable reproductive outcomes in true-NC FET with or without LPS ( 42 – 44 ). A RCT demonstrated that administration of progesterone (vaginal micronized progesterone 400 mg bid) from the day (LH surge+3 day) of true-NC FET (cleavage-stage embryos) had a higher LBR than no LPS ( 45 ).…”

Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review

“…In t-NC, regarding the available retrospective studies some favor LPS (82) whereas others report comparable reproductive outcomes with or without LPS (67,83,84).…”