ABSTRACT
Background: Luteal phase support is indicated after Controlled Ovarian Stimulation
(COS) using Long Gonadotropin-Releasing Hormone Agonist (GnRHa) protocol in Women undergoing in Vitro Fertilization (IVF)/Intracytoplasmic
Sperm Injection (ICSI). Progesterone is widely used for this indication. Objective: The objective of the current trial is to compare both efficacy and safety
of oral dydrogesterone and vaginal micronized progesterone in luteal phase
support in women undergoing IVF/ICSI using the long GnRHa protocol. Methods: This open-label randomized controlled study conducted at a private
fertility and IVF center in Zagazig, Egypt, during the interval between April
2016 and August 2019. The study included
women planned to undergo IVF/ICSI for either male factor infertility, tubal
factor infertility, or unexplained infertility. Women with pelvic
endometriosis, known reduced ovarian reserve, and women who were known to have
poor or high response to ovarian stimulation, as well as women who were
stimulated using non-long GnRHa protocol were not included. After embryo
transfer, eligible women were randomly allocated into one of the two groups:
group I, included women who received oral dydrogesterone 10 mg three times per
day; and group II, included women who received vaginal micronized progesterone
400 mg twice per day. The primary outcome was live birth rate. The principal
secondary outcome was women satisfaction. Results: Five hundred sixty
four women were recruited and randomly allocated into two groups: group I [Oral
Dydrogesterone Group] (n = 284), and group II [Vaginal Progesterone Group] (n = 280).
Live birth rates [72 (25.4%) vs 69 (24.6%), respectively, RR 1.03, 95% CI (0.77
to 1.37)], ongoing pregnancy rates [79 (27.8%) vs 81 (28.9%), respectively, RR
0.96, 95% CI (0.74 to 1.25)], clinical pregnancy rates [97 (34.2%) vs 95
(33.9%), respectively, RR 1.01, 95% CI (0.80 to 1.27)] and miscarriage rates
(per clinical pregnancy) [18 (18.6%) vs 14 (14.7%), respectively, RR 1.26, 95%
CI (0.66 to 2.38)] were all comparable in both groups. The rates of vaginal
burning [4 (1.4%) vs 32 (11.4%), respectively, RR 0.12, 95% CI (0.04 to 0.34)],
vaginal bleeding [9 (3.2%) vs 26 (9.3%), respectively, RR 0.34, 95% CI (0.16 to
0.72)] and overall dissatisfaction [15 (5.3%) vs 68 (24.3%), respectively, RR
0.22, 95% CI (0.13 to 0.37)] were significantly lower among women of group I
when compared to women of group II. Conclusion: In conclusion, when
compared to vaginal micronized progesterone, oral dydrogesterone seems to be
associated with comparable live birth, ongoing pregnancy and clinical pregnancy
rates, and significantly lower dissatisfaction and side effects rates, when
given as luteal phase support in normal responding women undergoing IVF/ICSI
using the long GnRHa protocol.