Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse
Por:
Salang, L, Teixeira, DM, Sola, I, Sothornwit, J, Martins, WP, Rodriguez, MB, Lumbiganon, P
Publicada:
1 ene 2022
Resumen:
Background
Ovulation induction may impact endometrial receptivity due to insufficient progesterone secretion. Low progesterone is associated with poor pregnancy outcomes.
Objectives
To assess the effectiveness and safety of luteal phase support (LPS) in infertile women trying to conceive by intrauterine insemination or by sexual intercourse.
Search methods
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).
Selection criteria
Randomised controlled trials (RCTs) of LPS using progestogen, human chorionic gonadotropin (hCG), or gonadotropin-releasing hormone (GnRH) agonist supplementation in IUI or natural cycle.
Data collection and analysis
We used standard methodological procedures expected by Cochrane. Our primary outcomes were live birth rate/ongoing pregnancy rate (LBR/OPR) and miscarriage.
Main results
We included 25 RCTs (5111 participants). Most studies were at unclear or high risk of bias. We graded the certainty of evidence as very low to low. The main limitations of the evidence were poor reporting and imprecision.
1. Progesterone supplement versus placebo or no treatment
We are uncertain if vaginal progesterone increases LBR/OPR (risk ratio (RR) 1.10, 95% confidence interval (CI) 0.81 to 1.48; 7 RCTs; 1792 participants; low-certainty evidence) or decreases miscarriage per pregnancy compared to placebo or no treatment (RR 0.70, 95% CI 0.40 to 1.25; 5 RCTs; 261 participants). There were no data on LBR or miscarriage with oral stimulation.
We are uncertain if progesterone increases LBR/OPR in women with gonadotropin stimulation (RR 1.24, 95% CI 0.80 to 1.92; 4 RCTs; 1054 participants; low-certainty evidence) and oral stimulation (clomiphene citrate or letrozole) (RR 0.97, 95% CI 0.58 to 1.64; 2 RCTs; 485 participants; low-certainty evidence). One study reported on OPR in women with gonadotropin plus oral stimulation; the evidence from this study was uncertain (RR 0.73, 95% CI 0.37 to 1.42; 1 RCT; 253 participants; low-certainty evidence). Given the low certainty of the evidence, it is unclear if progesterone reduces miscarriage per clinical pregnancy in any 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). Low-certainty evidence suggests that progesterone in all types of ovarian stimulation may increase clinical pregnancy compared to placebo (RR 1.38, 95% CI 1.10 to 1.74; 7 RCTs; 1437 participants, with gonadotropin; RR 1.40, 95% CI 1.03 to 1.90; 4 RCTs; 733 participants, with gonadotropin plus oral stimulation (clomiphene citrate or letrozole); and RR 1.44, 95% CI 1.04 to 1.98; 6 RCTs; 1073 participants, with oral stimulation).
2. Progesterone supplementation regimen
We are uncertain if there is any difference between 300 mg and 600 mg of vaginal progesterone for OPR and multiple pregnancy (RR 1.58, 95% CI 0.81 to 3.09; 1 RCT; 200 participants; very low-certainty evidence; and RR 0.50, 95% CI 0.05 to 5.43; 1 RCT; 200 participants, very low-certainty evidence, respectively). No other outcomes were reported for this comparison.
There were three different comparisons between progesterone regimens. For OPR, the evidence is very uncertain for intramuscular (IM) versus vaginal progesterone (RR 0.59, 95% CI 0.34 to 1.02; 1 RCT; 225 participants; very low-certainty evidence); we are uncertain if there is any diEerence between oral and vaginal progesterone (RR 1.25, 95% CI 0.70 to 2.22; 1 RCT; 150 participants; very low-certainty evidence) or between subcutaneous and vaginal progesterone (RR 1.05, 95% CI 0.54 to 2.05; 1 RCT; 246 participants; very low-certainty evidence). We are uncertain if IM or oral progesterone reduces miscarriage per clinical pregnancy compared to vaginal progesterone (RR 0.75, 95% CI 0.43 to 1.32; 1 RCT; 81 participants and RR 0.58, 95% CI 0.11 to 3.09; 1 RCT; 41 participants, respectively). Clinical pregnancy and multiple pregnancy were reported for all comparisons; the evidence for these outcomes was very uncertain. Only one RCT reported adverse effects. We are uncertain if IM route increases the risk of adverse effects when compared with the vaginal route (RR 9.25, 95% CI 2.21 to 38.78; 1 RCT; 225 participants; very low-certainty evidence).
3. GnRH agonist versus placebo or no treatment
No trials reported live birth. The evidence is very uncertain about the eEect of GnRH agonist in ongoing pregnancy (RR 1.10, 95% CI 0.70 to 1.74; 1 RCT; 291 participants, very low-certainty evidence), miscarriage per clinical pregnancy (RR 0.73, 95% CI 0.26 to 2.10; 2 RCTs; 79 participants, very low-certainty evidence) and clinical pregnancy (RR 1.00, 95% CI 0.68 to 1.47; 2 RCTs; 340 participants; very low-certainty evidence), and multiple pregnancy (RR 0.28, 95% CI 0.11 to 0.70; 2 RCTs; 126 participants).
4. GnRH agonist versus vaginal progesterone
The evidence for the effect of GnRH agonist injection on clinical pregnancy is very uncertain (RR 1.00, 95% CI 0.51 to 1.95; 1 RCT; 242 participants).
5. HCG injection versus no treatment
The evidence for the effect of hCG injection on clinical pregnancy (RR 0.93, 95% CI 0.40 to 2.13; 1 RCT; 130 participants) and multiple pregnancy rates (RR 1.03, 95% CI 0.22 to 4.92; 1 RCT; 130 participants) is very uncertain.
6. Luteal support in natural cycle
No study evaluated the effect of LPS in natural cycle.
We could not perform sensitivity analyses, as there were no studies at low risk of selection bias and not at high risk in other domains.
Authors' conclusions
We are uncertain if vaginal progesterone supplementation during luteal phase is associated with a higher live birth/ongoing pregnancy rate. Vaginal progesterone
Filiaciones:
Salang, L:
Khon Kaen Univ, Fac Med, Dept Obstet & Gynaecol, Khon Kaen, Thailand
Teixeira, DM:
Univ Fed Parana, Dept Obstet & Gynecol, Curitiba, Parana, Brazil
Sola, I:
CIBER Epidemiol & Salud Publ CIBERESP, Iberoamer Cochrane Ctr, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Sothornwit, J:
Khon Kaen Univ, Fac Med, Dept Obstet & Gynaecol, Khon Kaen, Thailand
Martins, WP:
SEMEAR Fertilidade, Reprod Med, Ribeirao Preto, Brazil
Rodriguez, MB:
Univ Auckland, Dept Obstet & Gynaecol, Auckland, New Zealand
Lumbiganon, P:
Khon Kaen Univ, Fac Med, Dept Obstet & Gynaecol, Khon Kaen, Thailand
|