Progestogens for prevention of luteinising hormone (LH) surge in women undergoing controlled ovarian hyperstimulation as part of an assisted reproductive technology (ART) cycle.
Currently, gonadotrophin releasing hormone (GnRH) analogues are used to prevent premature ovulation in ART cycles. However, their costs remain high, the route of administration is invasive and has some adverse effects. Oral progestogens could be cheaper and effective to prevent a premature LH surge.
To evaluate the effectiveness and safety of using progestogens to avoid spontaneous ovulation in women undergoing controlled ovarian hyperstimulation (COH).
We searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase and PsycINFO in Dec 2021. We contacted study authors and experts to identify additional studies.
We included randomised controlled trials (RCTs) that included progestogens for ovulation inhibition in women undergoing controlled ovarian hyperstimulation (COH).
We used standard methodological procedures recommended by Cochrane, including the risk of bias (RoB) assessment. The primary review outcomes were live birth rate (LBR) and oocyte pick-up cancellation rate (OPCR). Secondary outcomes were clinical pregnancy rate (CPR), cumulative pregnancy, miscarriage rate (MR), multiple pregnancies, LH surge, total and MII oocytes, days of stimulation, dose of gonadotropins, and moderate/severe ovarian hyperstimulation syndrome (OHSS) rate. The primary analyses were restricted to studies at overall low and some concerns RoB, and sensitivity analysis included all studies. We used the GRADE approach to assess the certainty of evidence.
We included 14 RCTs (2643 subfertile women undergoing ART, 47 women used oocyte freezing for fertility preservation and 534 oocyte donors). Progestogens versus GnRH antagonists We are very uncertain of the effect of medroxyprogesterone acetate (MPA) 10 mg compared with cetrorelix on the LBR in poor responders (odds ratio (OR) 1.25, 95% confidence interval (CI) 0.73 to 2.13, one RCT, N = 340, very-low-certainty evidence), suggesting that if the chance of live birth following GnRH antagonists is assumed to be 18%, the chance following MPA would be 14% to 32%. There may be little or no difference in OPCR between progestogens and GnRH antagonists, but due to wide Cs (CIs), we are uncertain (OR 0.92, 95%CI 0.42 to 2.01, 3 RCTs, N = 648, I² = 0%, low-certainty evidence), changing the chance of OPCR from 4% with progestogens to 2% to 8%. Given the imprecision found, no conclusions can be retrieved on CPR and MR. Low-quality evidence suggested that using micronised progesterone in normo-responders may increase by 2 to 6 the MII oocytes in comparison to GnRH antagonists. There may be little or no differences in gonadotropin doses. Progestogens versus GnRH agonists Results were uncertain for all outcomes comparing progestogens with GnRH agonists. One progestogen versus another progestogen The analyses comparing one progestogen versus another progestogen for LBR did not meet our criteria for primary analyses. The OPCR was probably lower in the MPA 10 mg in comparison to MPA 4 mg (OR 2.27, 95%CI 0.90 to 5.74, one RCT, N = 300, moderate-certainty evidence), and MPA 4 mg may be lower than micronised progesterone 100 mg, but due to wide CI, we are uncertain of the effect (OR 0.81, 95%CI 0.43 to 1.53, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 5% with MPA 4 mg to 5% to22%, and from 17% with micronised progesterone 100 mg to 8% to 24%. When comparing dydrogesterone 20 mg to MPA, the OPCR is probably lower in the dydrogesterone group in comparison to MPA 10 mg (OR 1.49, 95%CI 0.80 to 2.80, one RCT, N = 520, moderate-certainty evidence), and it may be lower in dydrogesterone group in comparison to MPA 4 mg but due to wide confidence interval, we are uncertain of the effect (OR 1.19, 95%CI 0.61 to 2.34, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 7% with dydrogesterone 20 to 6-17%, and in MPA 4 mg from 12% to 8% to 24%. When comparing dydrogesterone 20 mg to micronised progesterone 100 mg, the OPCR is probably lower in the dydrogesterone group (OR 1.54, 95%CI 0.94 to 2.52, two RCTs, N=550, I² = 0%, moderate-certainty evidence), changing OPCR from 11% with dydrogesterone to 10% to 24%. We are very uncertain of the effect in normo-responders of micronised progesterone 100 mg compared with micronised progesterone 200 mg on the OPCR (OR 0.35, 95%CI 0.09 to 1.37, one RCT, N = 150, very-low-certainty evidence). There is probably little or no difference in CPR and MR between MPA 10 mg and dydrogesterone 20 mg. There may be little or no differences in MII oocytes and gonadotropins doses. No cases of moderate/severe OHSS were reported in most of the groups in any of the comparisons.
Little or no differences in LBR may exist when comparing MPA 4 mg with GnRH agonists in normo-responders. OPCR may be slightly increased in the MPA 4 mg group, but MPA 4 mg reduces the doses of gonadotropins in comparison to GnRH agonists. Little or no differences in OPCR may exist between progestogens and GnRH antagonists in normo-responders and donors. However, micronised progesterone could improve by 2 to 6 MII oocytes. When comparing one progestogen to another, dydrogesterone suggested slightly lower OPCR than MPA and micronised progesterone, and MPA suggested slightly lower OPCR than the micronised progesterone 100 mg. Finally, MPA 10 mg suggests a lower OPCR than MPA 4 mg. There is uncertainty regarding the rest of the outcomes due to imprecision and no solid conclusions can be drawn.
Glujovsky D
，Pesce R
，Miguens M
，Sueldo C
，Ciapponi A
... -
《Cochrane Database of Systematic Reviews》
Oocyte activation for women following intracytoplasmic sperm injection (ICSI).
Intracytoplasmic sperm injection (ICSI), a type of assisted reproductive technology (ART), is offered as a treatment option for male factor infertility. Over the years, the indications for ICSI have been expanded, despite uncertainty about its benefits and harms compared to the conventional method of achieving fertilisation. Artificial oocyte activation (AOA), which can be performed by chemical, electrical or mechanical intervention, has been employed during ART ICSI treatment where there has been a history of low fertilization rate or total fertilization failure, and it has been reported to improve reproductive outcomes. It is important to evaluate the clinical effectiveness and safety of AOA in women undergoing ART ICSI treatment.
To evaluate the benefits and harms of artificial oocyte activation in women affected by infertility undergoing intracytoplasmic sperm injection treatment.
We searched the following electronic databases: the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO international Clinical Trials Registry Platform (8 August 2024). We also searched reference lists of relevant articles and contacted experts in the field.
Randomized controlled trials comparing artificial oocyte activation (AOA) (chemical, electrical or mechanical interventions) versus no intervention, placebo or another method of AOA in women undergoing ART.
We used methodological procedures as per Cochrane recommendations. We assessed the risk of bias in the included studies using ROB 2. The primary outcomes were live birth and miscarriage rates. We analyzed data using the risk ratio (RR) and a fixed-effect model. We assessed the certainty of the evidence by using GRADE criteria. We restricted the primary analyses to studies at low risk of bias.
We included a total of 20 studies, four of which were participant-based randomized trials with 743 participants. The remaining 16 were sibling-oocyte-model randomized studies. We based the main clinical findings of the current review on the participant-based RCTs, and we restricted our primary analysis to studies with a low risk of bias. Based on the one trial with 343 participants that we included in our primary analysis, the evidence is very uncertain about the effect of AOA on the live birth rate when compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.97, 95% CI 1.29 to 3.01; one trial; 343 participants). For a typical clinic with a live birth rate of 18% following ART, the addition of AOA may result in live birth rates between 24% and 55%, but this evidence is very uncertain. The evidence is very uncertain about the effect of AOA on the miscarriage rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 0.99, 95% CI 0.48 to 2.04; one trial; 343 participants). If the miscarriage rate was 9% following ART, addition of oocyte activation may result in miscarriage rates between 4% and 18%, but this evidence is very uncertain. The evidence is very uncertain about the effect of AOA on the clinical pregnancy rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.67, 95% CI 1.20 to 2.32; one trial; 343 participants). The evidence is very uncertain about the effect of AOA on the multiple pregnancy rate per participant compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.91, 95% CI 0.48 to 7.67; one trial; 343 participants). The evidence is very uncertain about the effect of AOA on the total fertilization failure rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 0.05, 95% CI 0.01 to 0.40; one trial; 343 participants). When we stratified our analysis according to various infertility factors, we found low-certainty evidence that in couples undergoing ICSI treatment who have had a history of low or no fertilization, AOA may help improve the live birth rate while making little or no difference to the miscarriage rate. Further research is needed to confirm or refute this finding. None of the trials reported congenital anomalies (birth defects) as an outcome. Lack of short- or long-term safety data is an important limitation of the review and of the trials in this field. We did not find any trials that compared two different methods of oocyte activation.
We are uncertain about the effect of AOA on the live birth and miscarriage rates in women undergoing ART ICSI. In the subpopulation of those who have had a previous history of low or no fertilization, AOA may result in an increase in the live birth rate when compared to conventional ICSI without AOA, while making little or no difference to the miscarriage rate. There was considerable variation in the protocols used for chemical AOA, which affects the generalizability of the findings. Due to the very low to low certainty of evidence, the results should be interpreted with caution.
Kamath MS
，Vogiatzi P
，Sunkara SK
，Woodward B
... -
《Cochrane Database of Systematic Reviews》
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