Vaginal versus intramuscular progesterone for luteal phase support in assisted reproductive techniques: a systematic review and meta-analysis of randomized controlled trials

Abdelhakim, Ahmed Mohamed; Abd-ElGawad, Mohamed; Hussein, Reda S.; Abbas, Ahmed M.

doi:10.1080/09513590.2020.1727879

Cited by 26 publications

(13 citation statements)

References 36 publications

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“…In a recent systematic review and meta-analysis of RCTs of vaginal vs. IM-P for LPS in ART, IM-P showed similar results in CPRs, OPRs, miscarriages, and LBRs [34]. Similar results were obtained in the updated Cochrane meta-analysis [7].…”

Section: Route Of Administration Intra-muscular (Im)supporting

confidence: 59%

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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Section: Route Of Administration Intra-muscular (Im)supporting

confidence: 59%

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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“… 4 , 12 , 13 , 14 In addition to the efficacy of the vaginal inserts being equivalent to that of intramuscular injection of P, the satisfaction of vaginal insert seems superior to that of the intramuscular injection. 15 …”

Section: Discussionmentioning

confidence: 99%

The addition of dydrogesterone improves the outcomes of pregnant women with low progesterone levels when receiving vaginal progesterone alone as luteal support in HRT‐FET cycles

Toriumi¹,

Horikawa²,

Sato³

et al. 2023

Reprod Medicine & Biology

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Purpose Vaginal progesterone (VP) alone has been used as luteal support (LS) in HRT‐FET cycles without measuring serum progesterone concentrations (SPC) because it can achieve adequate intrauterine progesterone levels. However, several reports showed that the co‐administration of progestin produced better outcomes than VP alone. We tried to address this discrepancy, focusing on SPC. Methods VP was given to 180 women undergoing HRT‐FET. We measured SPC when pregnancy was diagnosed on day 14 of LS. We compared assisted reproductive technology outcomes between VP alone versus VP + dydrogesterone (D). Results When using VP alone, average SPC in the miscarriage cases (9.6 ng/mL) were significantly lower compared with the ongoing pregnancy (OP) cases (14.7 ng/mL). The cut‐off value for progesterone, 10.7 ng/mL, was a good predictor for the subsequent course of the pregnancy. Of 76 women receiving D ± VP from the start of LS and achieving a pregnancy, the numbers of OP were 44 (84.6%) in SPC ≥ 10.7 ng/mL and 20 (83.3%) in SPC ≤ 10.7 ng/mL with no significant difference. Conclusion VP alone resulted in lower SPC in some pregnant women in HRT‐FET cycles and exhibited a lower OP rate. The co‐administration of D improved an OP rate of low progesterone cases to the level comparable with non‐low progesterone cases.

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“…In our reproductive center, we mainly applied three endometrial preparation protocols based on patient characteristics, preference and/or at the discretion of physician, as no regimen was superior to another for endometrial preparation in terms of clinical outcomes ( 30 – 32 ). The method of luteal phase support depends on patient’s preference, as there is no clear medical evidence that using one option is better than another ( 33 – 35 ). Intramuscular progesterone (40 mg once daily) or a combination of vaginal progesterone sustained-release gel (Crinone 8%, 90mg once daily) and oral progesterone (Dydrogesterone, 10 mg twice daily) was administered until 10 weeks of gestation.…”

Section: Methodsmentioning

confidence: 99%

Comparison of cumulative live birth rates between progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in different populations

et al. 2023

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ObjectiveTo compare cumulative live birth rate (LBR) between progestin-primed ovarian stimulation (PPOS) and GnRH antagonist protocols of preimplantation genetic testing (PGT) cycles in different populations.MethodsThis was a retrospective cohort study. A total of 865 patients were enrolled and separate analyses were performed for three populations: 498 patients with predicted normal ovarian response (NOR), 285 patients with PCOS, and 82 patients with predicted poor ovarian response (POR). The primary outcome was cumulative LBR for one oocyte retrieval cycle. The results of response to ovarian stimulation were also investigated, including numbers of oocytes retrieved, MII oocytes, 2PN, blastocysts, good-quality blastocysts, and usable blastocysts after biopsy, as well as rates of oocyte yield, blastocyst formation, good-quality blastocysts, and moderate or severe OHSS. Univariable and multivariable logistic regression analyses were used to identify potential confounders that may be independently associated with cumulative live birth.ResultsIn NOR, the cumulative LBR of PPOS protocol was significantly lower than that of GnRH antagonists (28.4% vs. 40.7%; P=0.004). In multivariable analysis, the PPOS protocol was negatively associated with cumulative LBR (adjusted OR=0.556; 95% CI, 0.377-0.822) compared to GnRH antagonists after adjusting for potential confounders. The number and ratio of good-quality blastocysts were significantly reduced in PPOS protocol compared to GnRH antagonists (2.82 ± 2.83 vs. 3.20 ± 2.79; P=0.032 and 63.9% vs. 68.5%; P=0.021), while numbers of oocytes, MII oocytes and 2PN did not show any significant difference between GnRH antagonist and PPOS protocols. PCOS patients had similar outcomes as NOR. The cumulative LBR of PPOS group appeared to be lower than that of GnRH antagonists (37.4% vs. 46.1%; P=0.151), but not significantly. Meanwhile, the proportion of good-quality blastocysts in PPOS protocol was also lower compared to GnRH antagonists (63.5% vs. 68.9%; P=0.014). In patients with POR, the cumulative LBR of PPOS protocol was comparable to that of GnRH antagonists (19.2% vs. 16.7%; P=0.772). There was no statistical difference in the number and rate of good-quality blastocysts between the two protocols in POR, while the proportion of good-quality blastocysts appeared to be higher in PPOS group compared to GnRH antagonists (66.7% vs. 56.3%; P=0.182). In addition, the number of usable blastocysts after biopsy was comparable between the two protocols in three populations.ConclusionThe cumulative LBR of PPOS protocol in PGT cycles is lower than that of GnRH antagonists in NOR. In patients with PCOS, the cumulative LBR of PPOS protocol appears to be lower than that of GnRH antagonists, albeit lacking statistical difference, whereas in patients with diminished ovarian reserve, the two protocols were comparable. Our findings suggest the need for caution when choosing PPOS protocol to achieve live births, especially for normal and high ovarian responders.

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Vaginal versus intramuscular progesterone for luteal phase support in assisted reproductive techniques: a systematic review and meta-analysis of randomized controlled trials

Cited by 26 publications

References 36 publications

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

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

The addition of dydrogesterone improves the outcomes of pregnant women with low progesterone levels when receiving vaginal progesterone alone as luteal support in HRT‐FET cycles

Comparison of cumulative live birth rates between progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in different populations

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