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

Abstract

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.

No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis

“…Dydrogesterone is one of only two available oral treatment options for the treatment of women at risk of miscarriage or RPL in the first trimester and those undergoing ART. In such a highly motivated population, patient preferences for the route of progestogen administration are likely to be a secondary consideration ( Shoham et al , 2021 ), but it is still important that patients should be offered a safe choice. For some patients, the requirements for vaginal administration (such as how and when to apply) and potential side effects (such as vaginal irritation, discharge, bleeding, and interference with coitus) may impact their effective use ( Licciardi et al , 1999 ; Czajkowski et al , 2007 ; Barbosa et al , 2016 ; Shoham et al , 2021 ; Parveen et al , 2021 ; Almohammadi et al , 2022 ).…”

The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET)

“…The use of subcutaneous progesterone for luteal phase support has become increasingly common in the past decade, although the vaginal and intramuscular routes remain the most used worldwide ( Shoham et al , 2021 ). While data comparing different dosages of the aqueous subcutaneous (25 mg OD versus 50 mg OD) have not identified differences in endometrial decidualisation ( de Ziegler et al , 2013 ), there remains a paucity of studies investigating pregnancy outcomes in women having luteal phase support with aqueous versus oil-based formulations.…”

Early-Pregnancy Dydrogesterone Supplementation Mimicking Luteal-Phase Support in ART Patients Did Not Provoke Major Reproductive Disorders in Pregnant Mice and Their Progeny

“…Controlled ovarian stimulation (COS) in assisted reproductive techniques (ART) often induces luteal insufficiency and thus provokes a P4 deficit. To overcome P4 scarcity, patients undergoing COS are routinely supplemented with exogenous progestogens through different routes, including oral, intramuscular, vaginal, and subcutaneous application forms [2]. P4 supplementation commonly starts on the day of or the day after egg collection, and is continued at least until the first positive pregnancy Int.…”

“…Sci. 2021, 22, 5403 2 of 18 test [2]. Additionally, progestogens are administered to patients with threatened or recurrent miscarriages during the first trimester to support successful pregnancy progression; however, the benefit of this treatment is controversially discussed [3].…”

“…Although the use of micronized P4 supplementation is effective and safe, the need of a vaginal or subcutaneous application is inconvenient for the majority of patients. Therefore, the use of dydrogesterone (DG), a biologically active metabolite of P4 with good oral bioavailability, has become an alternative to micronized P4 in clinical practice with a high level of patient compliance [2]. DG, as a synthetic progestogen, has to be supplemented until the 12th week of pregnancy, resembling the complete first trimester of pregnancy.…”