Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis

Melo, Pedro; Chung, Yealin; Pickering, Oonagh; Price, Malcolm J; Fishel, Simon; Khairy, Mohammed; Kingsland, Charles; Lowe, Philip; Πέτσας, Γεώργιος; Rajkhowa, Madhurima; Sephton, Victoria; Tozer, Amanda; Wood, Simon; Labarta, Elena; Wilcox, Mark; Devall, Adam J.; Gallos, Ioannis; Coomarasamy, Arri

doi:10.1016/j.fertnstert.2021.07.002

Cited by 71 publications

(43 citation statements)

References 75 publications

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“…There is no reason to believe that the SAS stimulation could reduce miscarriage by enhancing the ploidy rate, because recent studies show that ovarian stimulation does not impact the risk of aneuploidy ( 45 , 46 ). Other factors like individualized luteal support with adequate progesterone levels in FET might play a role ( 47 ), as it was most recently changed in our center.…”

Section: Discussionmentioning

confidence: 99%

“Short agonist stop” protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF): A pilot study

et al. 2022

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IntroductionPoor responder patients remain a challenge in assisted reproductive technologies. The “short agonist stop” (SAS) stimulation protocol uses a double stimulation (flare up effect with the gonadotropin-releasing hormone (GnRH) agonist (GnRH-a) then gonadotropins) associated with a less strenuous blockage (discontinuation of GnRH-a) to favor follicular recruitment in order to obtain a better ovarian response. This study aims to compare the number of oocytes obtained after a SAS stimulation protocol with those obtained after the previous stimulation protocol, in the same women, with poor ovarian response (POR) diagnosed according to the POSEIDON criteria.DesignThis therapeutic observational retrospective cohort from 2018 to 2022, with a case-control evaluation compared with the same patients’ previous performance, included women with POR undergoing IVF with SAS stimulation protocol. The primary outcome was the number of total oocytes recovered and secondary outcomes were the numbers of mature oocytes, total embryos observed at day 2 and usable cleaved embryos and blastocysts (day 5/6).Results63 patients with SAS and previous cycles were included. In the SAS group, the mean number of oocytes was significantly higher: 7.3 vs 5.7, p=0.018 in comparison with the previous attempt. So was the number of mature oocytes (5.8 vs 4.1, p=0.032) and the total mean number of embryos obtained at day 2 (4.1 versus 2.7, p=0.016). The SAS stimulation generated 84 usable embryos: 57 cleaved embryos and 27 blastocysts. The mean number of usable embryos was similar in both groups (1.64 vs 1.31, respectively, p=0.178). In total, out of 63 patients, after the SAS protocol, and subsequent embryo transfers (fresh and frozen, n=54), 9 patients had ongoing pregnancies and no miscarriage occurred. The cumulative ongoing pregnancy rate (cOPR) after the SAS protocol was 14.3% (9/63) per oocyte pick-up and 16.7% (9/54) per transfer.ConclusionSAS stimulation is a short and original protocol strengthening the therapeutic arsenal of poor responders, that may offer promising results for those patients with low prognosis and previous failed IVF. Results must be confirmed with a randomized controlled trial.

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Section: Discussionmentioning

confidence: 99%

“Short agonist stop” protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF): A pilot study

et al. 2022

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“…Progesterone plays a crucial role in the secretory transformation of the endometrium and in the opening of the implantation window. Many studies showed a negative impact of low serum concentration of progesterone in the mid-luteal phase on the reproductive outcomes (6,7,9,(12)(13)(14)(15)(16)(17). Therefore, we hypothesized that early implementation of a rescue protocol to increase its concentration should optimize endometrial receptivity and maximize reproductive outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Other implicated factors are the interval between blood sampling and last VMP intake, or sexual intercourse (4,11). Recent studies reported a negative impact of low serum progesterone concentration in the luteal phase on reproductive outcomes in HRT cycles (6,7,9,(12)(13)(14)(15)(16)(17). Progesterone concentration was assessed at different points of the HRT cycle (from the day before embryo transfer to the day of pregnancy test or later), but pharmacokinetic studies showed that progesterone concentration reaches a plateau within 24-36h after VMP administration (18).…”

Section: Introductionmentioning

confidence: 99%

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Individualized luteal phase support based on serum progesterone levels in frozen-thawed embryo transfer cycles maximizes reproductive outcomes in a cohort undergoing preimplantation genetic testing

Boulet¹,

Ranisavljevic²,

Mollevi³

et al. 2022

Front. Endocrinol.

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IntroductionLow serum progesterone concentration on frozen embryo transfer (FET) day in hormone replacement therapy (HRT) cycles results in lower reproductive outcomes. Recent studies showed the efficiency of a “rescue protocol’’ to restore reproductive outcomes in these patients. Here, we compared reproductive outcomes in HRT FET cycles in women with low serum progesterone levels who received individualized luteal phase support (iLPS) and in women with adequate serum progesterone levels who underwent in vitro fertilization for pre-implantation genetic testing for structural rearrangements or monogenic disorders.DesignThis retrospective cohort study included women (18-43 years of age) undergoing HRT FET cycles with pre-implantation genetic testing at Montpellier University Hospital between June 2020 and May 2022. A standard HRT was used: vaginal micronized estradiol (6mg/day) followed by vaginal micronized progesterone (VMP; 800 mg/day). Serum progesterone was measured after four doses of VMP: if <11ng/ml, 25mg/day subcutaneous progesterone or 30mg/day oral dydrogesterone was introduced.Results125 HRT FET cycles were performed in 111 patients. Oral/subcutaneous progesterone supplementation concerned 39 cycles (n=20 with subcutaneous progesterone and n=19 with oral dydrogesterone). Clinical and laboratory parameters of the cycles were comparable between groups. The ongoing pregnancy rate (OPR) was 41.03% in the supplemented group and 18.60% in the non-supplemented group (p= 0.008). The biochemical pregnancy rate and miscarriages rate tended to be higher in the non-supplemented group versus the supplemented group: 13.95% versus 5.13% and 38.46% versus 15.79% (p=0.147 and 0.182 respectively). Multivariate logistic regression analysis found that progesterone supplementation was significantly associated with higher OPR (adjusted OR = 3.25, 95% CI [1.38 – 7.68], p=0.007).ConclusionIn HRT FET cycles, progesterone supplementation in patients with serum progesterone concentration <11 ng/mL after four doses of VMP significantly increases the OPR.

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“…More homogeneous thresholds between studies would probably allow a more accurate interpretation of the results. Some authors suggested that a luteal serum progesterone above 10 ng/ml may be a minimum required to ensure the best chance of implantation and ongoing pregnancy (59). However, too high progesterone levels might be associated with decreased implantation rate (11,13).…”

Section: No Corpus Luteummentioning

confidence: 99%

Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses

Ranisavljevic

Huberlant

Montagut³

et al. 2022

Front. Endocrinol.

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Progesterone plays a key role in implantation. Several studies reported that lower luteal progesterone levels might be related to decreased chances of pregnancy. This systematic review was conducted using appropriate key words, on MEDLINE, EMBASE, and the Cochrane Library, from 1990 up to March 2021 to assess if luteal serum progesterone levels are associated with ongoing pregnancy (OP) and live birth (LB) rates (primary outcomes) and miscarriage rate (secondary outcome), according to the number of corpora lutea (CLs). Overall 2,632 non-duplicate records were identified, of which 32 relevant studies were available for quantitative analysis. In artificial cycles with no CL, OP and LB rates were significantly decreased when the luteal progesterone level falls below a certain threshold (risk ratio [RR] 0.72; 95% confidence interval [CI] 0.62–0.84 and 0.73; 95% CI 0.59–0.90, respectively), while the miscarriage rate was increased (RR 1.48; 95% CI 1.17–1.86). In stimulated cycles with several CLs, the mean luteal progesterone level in the no OP and no LB groups was significantly lower than in the OP and LB groups [difference in means 68.8 (95% CI 45.6–92.0) and 272.4 (95% CI 10.8–533.9), ng/ml, respectively]. Monitoring luteal serum progesterone levels could help in individualizing progesterone administration to enhance OP and LB rates, especially in cycles without corpus luteum.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139019, identifier 139019.

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Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis

Cited by 71 publications

References 75 publications

“Short agonist stop” protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF): A pilot study

“Short agonist stop” protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF): A pilot study

Individualized luteal phase support based on serum progesterone levels in frozen-thawed embryo transfer cycles maximizes reproductive outcomes in a cohort undergoing preimplantation genetic testing

Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses

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