P-392 Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse
Authors: Salang L , Teixeira D  M , Solà I , Sothornwit J , Martins W  P , Rodriguez M  B , Lumbiganon P  L 
Published: July 2024

Study question

Is luteal phase support (LPS) necessary for intrauterine insemination or sexual intercourse?

Summary answer

Vaginal progesterone supplementation during luteal phase may increase live birth (LBR)/ongoing pregnancy rate (OPR), however, its effect on miscarriage per pregnancy (MPP) is uncertain.

What is known already

Ovulation induction may impact endometrial receptivity due to insufficient progesterone secretion. Low progesterone is associated with poor pregnancy outcomes.

Study design, size, duration

Systematic reviews and meta-analysis were conducted. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, LILACS, trial registries for ongoing trials, and reference lists of articles (from inception to 25 August 2021).

Participants/materials, setting, methods

Randomised controlled trials (RCTs) of LPS using progestogen, human chorionic gonadotropin (hCG), or gonadotropin-releasing hormone (GnRH) agonist supplementation in IUI or natural cycle. We used the standard methodological procedures expected by Cochrane.

Main results and the role of chance

We included 25 RCTs (5111 participants).

Progesterone supplementation versus placebo or no treatment

Vaginal progesterone does not significantly increase the LBR/ OPR (RR 1.10, 95% confidence interval (CI) 0.81 to 1.48; 7 RCTs; 1792 participants;) or decrease MPP (RR 0.70, 95% CI 0.40 to 1.25; 5 RCTs; 261 participants). Subgroup analysis revealed that progesterone may not increase LBR/OPR in women with gonadotropin stimulation (RR 1.24, 95% CI 0.80 to 1.92; 4 RCTs; 1054 participants) and oral stimulation (clomiphene citrate or letrozole) (RR 0.97, 95% CI 0.58 to 1.64; 2 RCTs; 485 participants). In addition, progesterone may not reduce MPP regardless of stimulation protocol (RR 0.68, 95% CI 0.24 to 1.91; 2 RCTs; 102 participants, with gonadotropin; RR 0.67, 95% CI 0.30 to 1.50; 2 RCTs; 123 participants, with gonadotropin plus oral stimulation; and RR 0.53, 95% CI 0.25 to 1.14; 2 RCTs; 119 participants, with oral stimulation).

Different routes of progesterone administration versus vaginal route

There is no difference in terms of LBR, OPR, and MPP when comparing intramuscular (IM), oral, or subcutaneous progesterone to vaginal progesterone. Very low-certainty evidence suggests that intramuscular progesterone may lead to a substantial increase in adverse events, particularly pain at the site of injection.

Limitations, reasons for caution

Most studies were at unclear or high risk of bias. The main limitations of the evidence were poor reporting and imprecision.

Wider implications of the findings

Vaginal progesterone does not significantly increase in LBR/OPR or decrease miscarriage rate. In comparison to vaginal progesterone, there is insufficient data to evaluate whether progesterone supplementation via an alternative route has an impact on pregnancy outcomes.

Trial registration number

PROSPERO2017 CRD42017055106