Systematic Review of the Clinical Efficacy of Vaginal Progesterone for Luteal Phase Support in Assisted Reproductive Technology Cycles

Child, Tim; Leonard, Saoirse; Evans, JS; Lass, Amir

doi:10.1097/ogx.0000000000000610

Cited by 9 publications

(13 citation statements)

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“…Our systematic review found seven articles evaluating effects of progesterone in second or third trimester for preterm birth prevention, and however, no RCTs evaluated effects of progesterone in first trimester for luteal phase support. Progesterone is frequently employed for this indication, with over 90% of ART cycles worldwide reporting the use of progesterone as luteal phase support in 2013 5 . More importantly, trials evaluating progesterone as luteal phase support in ART generally consider ongoing pregnancy or live birth rate as primary outcome(s), with limited neonatal outcomes reported 4,5,46 .…”

Section: Discussionmentioning

confidence: 99%

“…International guidelines advise progesterone as luteal phase support for assisted reproductive technologies (ART) and for preterm birth prevention. The exact percentage of pregnancies in which progesterone is employed is estimated at 5-12% of all pregnancies (around 2-3% of babies are born through ART in western countries 5 and the incidence of preterm birth is 5-12%). 44,45 The expanding list of indications for progesterone in pregnancy have led to growing numbers of children being exposed to progesterone at various stages of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…Progesterone is frequently employed for this indication, with over 90% of ART cycles worldwide reporting the use of progesterone as luteal phase support in 2013. 5 More importantly, trials evaluating progesterone as luteal phase support in ART generally consider ongoing pregnancy or live birth rate as primary outcome(s), with limited neonatal outcomes reported. 4,5,46 Recent observational studies found an increased rate of large for gestational age or macrosomia in singletons after frozen embryo transfer with a programmed cycle (oestrogen and progesterone) and luteal phase support, as compared to natural or stimulated cycles.…”

Section: Discussionmentioning

confidence: 99%

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The long‐term effect of prenatal progesterone treatment on child development, behaviour and health: a systematic review

Simons

Leeuw

Hooft

et al. 2020

BJOG

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Background Progesterone is widely used in prenatal care. However, long-term effects of prenatal progesterone treatment on child development are unclear. Objectives To evaluate long-term outcomes in children after prenatal progesterone treatment. Search strategy MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to 24 May 2020. Selection criteria Randomised controlled trials (RCTs) reporting outcomes in children born to women who received progesterone treatment (compared with placebo or another intervention) during any trimester in pregnancy. Data collection and analysis Two authors independently selected and extracted data. We used the Cochrane Risk of Bias tool for randomised trials and Quality In Prognosis Studies. Main results Of 388 papers, we included seven articles based on five RCTs, comprising 4222 measurements of children aged 6 months to 8 years. All studies compared progesterone to placebo in second and/or third trimester for the prevention of preterm birth. Meta-analysis (two studies, n = 890 children) showed no difference in neurodevelopment as assessed by the Bayley-III Cognitive Composite score at 2 years between children exposed to progesterone versus placebo (Standardised Mean Difference À0.04, 95% Confidence Interval À0.26 to 0.19), I 2 = 22%. Heterogeneity prohibited additional meta-analyses. Other long-term outcomes showed no differences. Conclusions Our systematic review comprising a multitude of developmental measurements with a broad age range did not find evidence of benefit or harm in offspring prenatally exposed to progesterone treatment for the prevention of preterm birth. We identified an urgent need for follow-up studies of prenatal progesterone administration in early pregnancy and effects in offspring beyond early childhood.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The long‐term effect of prenatal progesterone treatment on child development, behaviour and health: a systematic review

Simons

Leeuw

Hooft

et al. 2020

BJOG

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“…A comparison between vaginal/rectal and IM-P routes in the updated Cochrane meta-analysis reported no difference in LBR (4 RCTs, 1, 222 patients, OR 1.17, 95 % CI 0.91 to 1.51) [7]. A recent systemic review of 18 trials comparing 4 vaginal P products have shown that there are no significant differences in efficacy or safety between the products [38].…”

Section: Vaginal Progesteronementioning

confidence: 99%

A 10-year follow‐up on the practice of luteal phase support using worldwide web‐based surveys

Shoham

Leong²,

Weissman

2021

Reprod Biol Endocrinol

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Background It has been demonstrated that luteal phase support (LPS) is crucial in filling the gap between the disappearance of exogenously administered hCG for ovulation triggering and the initiation of secretion of endogenous hCG from the implanting conceptus. LPS has a pivotal role of in establishing and maintaining in vitro fertilization (IVF) pregnancies. Over the last decade, a plethora of studies bringing new information on many aspects of LPS have been published. Due to lack of consent between researchers and a dearth of robust evidence-based guidelines, we wanted to make the leap from the bench to the bedside, what are the common LPS practices in fresh IVF cycles compared to current evidence and guidelines? How has expert opinion changed over 10 years in light of recent literature? Methods Over a decade (2009–2019), we conducted 4 web-based surveys on a large IVF-specialist website on common LPS practices and controversies. The self-report, multiple-choice surveys quantified results by annual IVF cycles. Results On average, 303 IVF units responded to each survey, representing, on average, 231,000 annual IVF cycles. Most respondents in 2019 initiated LPS on the day of, or the day after egg collection (48.7 % and 36.3 %, respectively). In 2018, 72 % of respondents administered LPS for 8–10 gestational weeks, while in 2019, 65 % continued LPS until 10–12 weeks. Vaginal progesterone is the predominant delivery route; its utilization rose from 64 % of cycles in 2009 to 74.1 % in 2019. Oral P use has remained negligible; a slight increase to 2.9 % in 2019 likely reflects dydrogesterone’s introduction into practice. E2 and GnRH agonists are rarely used for LPS, as is hCG alone, limited by its associated risk of ovarian hyperstimulation syndrome (OHSS). Conclusions Our Assisted reproductive technology (ART)-community survey series gave us insights into physician views on using progesterone for LPS. Despite extensive research and numerous publications, evidence quality and recommendation levels are surprisingly low for most topics. Clinical guidelines use mostly low-quality evidence. There is no single accepted LPS protocol. Our study highlights the gaps between science and practice and the need for further LPS research, with an emphasis on treatment individualization.

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“…Progesterone used for luteal phase support (derived from several species of Dioscorea, widely known as the yam plant [9]) can be formulated for intramuscular, oral, subcutaneous, or vaginal administration [10][11][12][13]. No progesterone formulation has, as yet, been shown to be superior in terms of efficacy [8,14,15], while tolerability and safety profiles vary according to the route of administration [10]. For example, although easier for the patient to use, orally administered micronized progesterone is rapidly metabolized by the liver and is associated with drowsiness, flushing, and nausea [10].…”

Section: Introductionmentioning

confidence: 99%

A Phase III randomized controlled trial of oral dydrogesterone versus intravaginal progesterone gel for luteal phase support in in vitro fertilization (Lotus II): results from the Chinese mainland subpopulation

Yang

Griesinger

Wang

et al. 2019

Gynecological Endocrinology

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Lotus II, a randomized, open-label, multicenter, international study compared the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) gel for luteal support in IVF. A prespecified subgroup analysis was performed on 239 Chinese mainland subjects from the overall study population (n ¼ 1034), who were randomized to oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily from the day of oocyte retrieval until 12 weeks of gestation. The aim was to demonstrate non-inferiority of oral dydrogesterone to MVP gel, assessed by the presence of a fetal heartbeat at 12 weeks of gestation. In the Chinese mainland subpopulation, there was a numerical difference of 9.4% in favor of oral dydrogesterone, with ongoing pregnancy rates at 12 weeks of gestation of 61.4% and 51.9% in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 9.4%; 95% CI: À3.4 to 22.1); in the overall population, these were 38.7% and 35%, respectively (adjusted difference, 3.7%; 95% CI: À2.3 to 9.7). In both the Chinese mainland subpopulation and the overall population, dydrogesterone had similar efficacy and safety to MVP gel. With convenient oral administration, dydrogesterone has potential to transform luteal support treatment.

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Systematic Review of the Clinical Efficacy of Vaginal Progesterone for Luteal Phase Support in Assisted Reproductive Technology Cycles

Cited by 9 publications

References 0 publications

The long‐term effect of prenatal progesterone treatment on child development, behaviour and health: a systematic review

The long‐term effect of prenatal progesterone treatment on child development, behaviour and health: a systematic review

A 10-year follow‐up on the practice of luteal phase support using worldwide web‐based surveys

A Phase III randomized controlled trial of oral dydrogesterone versus intravaginal progesterone gel for luteal phase support in in vitro fertilization (Lotus II): results from the Chinese mainland subpopulation

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