The strength of evidence supporting luteal phase progestogen after assisted reproduction: A systematic review with reference to trial registration and pre-specified endpoints

Suthaporn, Sutham; Jayaprakasan, Kanna; Maalouf, Walid E.; Thornton, Jim; Walker, Kate F.

doi:10.1016/j.ejogrb.2019.12.002

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…Exogenous progesterone supplementation has commonly been used for supporting the luteal phase; however, the route of progesterone administration is still controversial (10).…”

Section: The Luteal Phase Support In Hcg Triggered Fresh Transfer Cycle 21 Progesteronementioning

confidence: 99%

Luteal-phase support in assisted reproductive technology: An ongoing challenge

Dashti¹,

Eftekhar²

2021

IJRM

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It has been shown that in controlled ovarian hyper stimulation cycles, defective luteal phase is common. There are many protocols for improving pregnancy outcomes in women undergoing fresh and frozen in vitro fertilization cycles. These approaches include progesterone supplements, human chorionic gonadotropin, estradiol, gonadotropin-releasing hormone agonist, and recombinant luteinizing hormone. The main challenge is luteal-phase support (LPS) in cycles with gonadotropin-releasing hormone agonist triggering. There is still controversy about the optimal component and time for starting LPS in assisted reproductive technology cycles. This review aims to summarize the various protocols suggested for LPS in in vitro fertilization cycles. Key words: Luteal-phase support, IVF, HCG, Progesterone, GnRH agonist, Recombinant LH.

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“…Exogenous progesterone supplementation has commonly been used for supporting the luteal phase; however, the route of progesterone administration is still controversial (10).…”

Section: The Luteal Phase Support In Hcg Triggered Fresh Transfer Cycle 21 Progesteronementioning

confidence: 99%

Luteal-phase support in assisted reproductive technology: An ongoing challenge

Dashti¹,

Eftekhar²

2021

IJRM

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“…In natural ovulatory cycles, the corpus luteum can produce adequate progesterone after ovulation until the placental function starts at seven weeks of gestation. Ovarian stimulation (OS) techniques, either with gonadotropin-releasing hormone (GnRH) agonist or antagonist protocols, often induce endocrine defects in the luteal phase with increasing evidence suggesting that the resulting luteal-phase dysfunction may lead to lower pregnancy rates in in vitro fertilization (IVF) and/or ICSI (intracytoplasmic sperm injection) cycles 1 , 2 . To counteract these effects, luteal-phase support (LPS) is a well-known intervention for almost all stimulated assisted reproductive technology (ART) cycles 3 .…”

Section: Introductionmentioning

confidence: 99%

Comparison of luteal support protocols in fresh IVF/ICSI cycles: a network meta-analysis

Kastora,

Gkova,

Stavridis

et al. 2024

Sci Rep

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Despite the proven superiority of various luteal phase support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles, there is ongoing controversy over specific LPS protocol selection, dosage, and duration. The aim of the present study was to identify the optimal LPS under six core aspects of ART success, clinical pregnancy, live birth as primary outcomes and biochemical pregnancy, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS) events as secondary outcomes. Twelve databases, namely Embase (OVID), MEDLINE (R) (OVID), GlobalHealth (Archive), GlobalHealth, Health and Psychosocial Instruments, Maternity & Infant Care Database (MIDIRS), APA PsycTests, ClinicalTrials.gov, HMIC Health Management Information Consortium, CENTRAL, Web of Science, Scopus and two prospective registers, MedRxiv, Research Square were searched from inception to Aug.1st, 2023, (PROSPERO Registration: CRD42022358986). Only Randomised Controlled Trials (RCTs) were included. Bayesian network meta-analysis (NMA) model was employed for outcome analysis, presenting fixed effects, odds ratios (ORs) with 95% credibility intervals (CrIs). Vaginal Progesterone (VP) was considered the reference LPS given its’ clinical relevance. Seventy-six RCTs, comparing 22 interventions, and including 26,536 participants were included in the present NMA. Overall CiNeMa risk of bias was deemed moderate, and network inconsistency per outcome was deemed low (Multiple pregnancy χ2: 0.11, OHSS χ2: 0.26), moderate (Clinical Pregnancy: χ2: 7.02, Live birth χ2: 10.95, Biochemical pregnancy: χ2: 6.60, Miscarriage: χ2: 11.305). Combinatorial regimens, with subcutaneous GnRH-a (SCGnRH-a) on a vaginal progesterone base and oral oestrogen (OE) appeared to overall improve clinical pregnancy events; VP + OE + SCGnRH-a [OR 1.57 (95% CrI 1.11 to 2.22)], VP + SCGnRH-a [OR 1.28 (95% CrI 1.05 to 1.55)] as well as live pregnancy events, VP + OE + SCGnRH-a [OR 8.81 (95% CrI 2.35 to 39.1)], VP + SCGnRH-a [OR 1.76 (95% CrI 1.45 to 2.15)]. Equally, the progesterone free LPS, intramuscular human chorionic gonadotrophin, [OR 9.67 (95% CrI 2.34, 73.2)] was also found to increase live birth events, however was also associated with an increased probability of ovarian hyperstimulation, [OR 1.64 (95% CrI 0.75, 3.71)]. The combination of intramuscular and vaginal progesterone was associated with higher multiple pregnancy events, [OR 7.09 (95% CrI 2.49, 31.)]. Of all LPS protocols, VP + SC GnRH-a was found to significantly reduce miscarriage events, OR 0.54 (95% CrI 0.37 to 0.80). Subgroup analysis according to ovarian stimulation (OS) protocol revealed that the optimal LPS across both long and short OS, taking into account increase in live birth and reduction in miscarriage as well as OHSS events, was VP + SCGnRH-a, with an OR 2.89 [95% CrI 1.08, 2.96] and OR 2.84 [95% CrI 1.35, 6.26] respectively. Overall, NMA data suggest that combinatorial treatments, with the addition of SCGnRH-a on a VP base result in improved clinical pregnancy and live birth events in both GnRH-agonist and antagonist ovarian stimulation protocols.

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Evaluating interventions and adjuncts to optimize pregnancy outcomes in subfertile women: an overview review

Holt-Kentwell

Ghosh

Devall

et al. 2022

Human Reproduction Update

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BACKGROUND There is a wealth of information regarding interventions for treating subfertility. The majority of studies exploring interventions for improving conception rates also report on pregnancy outcomes. However, there is no efficient way for clinicians, researchers, funding organizations, decision-making bodies or women themselves to easily access and review the evidence for the effect of adjuvant therapies on key pregnancy outcomes in subfertile women. OBJECTIVE AND RATIONALE The aim was to summarize all published systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions in the subfertile population, specifically reporting on the pregnancy outcomes of miscarriage and live birth. Furthermore, we aimed to highlight promising interventions and areas that need high-quality evidence. SEARCH METHODS We searched the Cochrane Database of Systematic Reviews and PubMed clinical queries SR filter (inception until July 2021) with a list of key words to capture all SRs specifying or reporting any miscarriage outcome. Studies were included if they were SRs of RCTs. The population was subfertile women (pregnant or trying to conceive) and any intervention (versus placebo or no treatment) was included. We adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for determining the quality of the evidence. Exclusion criteria were overview reviews, reviews that exclusively reported on women conceiving via natural conception, reviews including non-randomized study designs or reviews where miscarriage or live birth outcomes were not specified or reported. OUTCOMES The primary outcome was miscarriage, defined as pregnancy loss <24 weeks of gestation. Data were also extracted for live birth where available. We included 75 published SRs containing 121 251 participants. There were 14 classes of intervention identified: luteal phase, immunotherapy, anticoagulants, hCG, micronutrients, lifestyle, endocrine, surgical, pre-implantation genetic testing for aneuploidies (PGT-As), laboratory techniques, endometrial injury, ART protocols, other adjuncts/techniques in the ART process and complementary interventions. The interventions with at least moderate-quality evidence of benefit in reducing risk of miscarriage or improving the chance of a live birth are: intrauterine hCG at time of cleavage stage embryo transfer, but not blastocyst transfer, antioxidant therapy in males, dehydroepiandrosterone in women and embryo medium containing high hyaluronic acid. Interventions showing potential increased risk of miscarriage or reduced live birth rate are: embryo culture supernatant injection before embryo transfer in frozen cycles and PGT-A with the use of fluorescence in situ hybridization. WIDER IMPLICATIONS This review provides an overview of key pregnancy outcomes from published SRs of RCTs in subfertile women. It provides access to concisely summarized information and will help clinicians and policy makers identify knowledge gaps in the field, whilst covering a broad range of topics, to help improve pregnancy outcomes for subfertile couples. Further research is required into the following promising interventions: the dose of progesterone for luteal phase support, peripheral blood mononuclear cells for women with recurrent implantation failure, glucocorticoids in women undergoing IVF, low-molecular-weight heparin for unexplained subfertility, intrauterine hCG at the time of cleavage stage embryo or blastocyst transfer and low oxygen concentrations in embryo culture. In addition, there is a need for high-quality, well-designed RCTs in the field of reproductive surgery. Finally, further research is needed to demonstrate the integrated effects of non-pharmacological lifestyle interventions.

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The strength of evidence supporting luteal phase progestogen after assisted reproduction: A systematic review with reference to trial registration and pre-specified endpoints

Cited by 3 publications

References 34 publications

Luteal-phase support in assisted reproductive technology: An ongoing challenge

Luteal-phase support in assisted reproductive technology: An ongoing challenge

Comparison of luteal support protocols in fresh IVF/ICSI cycles: a network meta-analysis

Evaluating interventions and adjuncts to optimize pregnancy outcomes in subfertile women: an overview review

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