Luteal phase progesterone and oestradiol after ovarian stimulation: relation to response and prediction of pregnancy

Petersen, Johannes F.; Andersen, Anders Nyboe; Klein, Bjarke M.; Helmgaard, L.; Arce, Joan‐Carles

doi:10.1016/j.rbmo.2017.12.019

Cited by 17 publications

(16 citation statements)

References 27 publications

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“…In the current study, the final follicle count >11mm was found in the regression analysis to significantly reduce LBR in HR (> 18 follicles) when compared with poor and intermediate responders [OR: 0.10, 95% CI, 0.03-0.33] (Table 3), which is consistent with the findings reported by a recent study showing a steady reduction in LBR beyond twenty oocytes retrieved, presumably due to supraphysiological circulating steroids levels [35]. Besides, the present data show a significant correlation between the ovarian response and both preovulatory and midluteal P 4 levels (S1 Table ) suggesting that each follicle contributes to the pool of serum P 4 before ovulation triggering [20,36] as well as after oocyte retrieval [24,37]. Contrasting the preovulatory serum P 4 level, the current results suggest that the midluteal P 4 level is an independent factor associated with LB potential, and, interestingly, in a nonlinear pattern, [OR: 2.73 (1.29-5.78); p< 0.008] (Table 3).…”

Section: Discussionsupporting

confidence: 92%

The impact of preovulatory versus midluteal serum progesterone level on live birth rates during fresh embryo transfer

Benmachiche¹,

Benbouhedja²,

Zoghmar³

et al. 2021

PLoS ONE

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Background Conflicting evidence still prevails concerning the effect of preovulatory elevated progesterone (EP4) on reproductive outcomes in fresh embryo transfer (ET). However, few studies have analyzed the effect of EP4 on the likelihood of pregnancy using multivariate regression approach. The potential confounding factors tested in these studies were limited to either patient’s characteristics or to stimulation related parameters. Yet, several studies have shown that postovulatory parameters such as midluteal progesterone (P4) level may be considered as a proxy variable of endometrial receptivity as well. Objective The aim of the present study was to estimate the independent effect of preovulatory P4 effect, if any, on the probability of live birth (LB) by considering the midluteal endocrine profile when controlling for the potential confounding factors. Methods This is a secondary data analysis of a cohort of fresh IVF/ICSI cycles triggered with GnRH agonist (n = 328) performed in a single IVF center during the period 2014–2016. Patients contributed only one cycle and were stratified into four groups according to preovulatory P4 quartiles. We assessed the association between preovulatory P4 and the odds of LB calculated by logistic regression analysis after controlling for the most clinically relevant confounders. The primary outcome measure: Live birth rates (LBR). Results Both preovulatory and midluteal P4 were significantly correlated with the ovarian response. Logistic regression analysis showed that preovulatory serum P4 did not have a significant impact on LBR. In contrast, midluteal serum P4 level was an important independent factor associated with LBR. The optimal chance of LBR was achieved with midluteal serum P4 levels of 41–60 ng/ml, [OR: 2.73 (1.29–5.78); p< 0.008]. Conclusion The multivariate analysis suggests that the midluteal P4 level seems to impact LBR more than the preovulatory P4 level in women undergoing IVF treatment followed by fresh ET.

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Section: Discussionsupporting

confidence: 92%

The impact of preovulatory versus midluteal serum progesterone level on live birth rates during fresh embryo transfer

Benmachiche¹,

Benbouhedja²,

Zoghmar³

et al. 2021

PLoS ONE

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“…The correlation between serum P levels on the day of the pregnancy test and pregnancy outcome has been also studied in stimulated cycles, with contradictive results. While some authors suggest that serum P can have a predictive role (8,9), others could not find this association (10). The difficulty in these stimulated cycles relies on the fact that the endocrine profile depends on the ovarian response, type of trigger and luteal phase support (11)(12)(13)(14), and this could influence the interpretation of results.…”

Section: Discussionmentioning

confidence: 99%

Serum Progesterone Profile Across the Mid and Late Luteal Phase in Artificial Cycles Is Associated With Pregnancy Outcome

Labarta

Rodríguez-Varela

Mariani³

et al. 2021

Front. Endocrinol.

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IntroductionRecent studies have shown that low serum progesterone levels on the day of embryo transfer (ET) are associated with poorer pregnancy outcome in hormonal replacement therapy cycles. It is of interest to know if serum progesterone levels during late luteal phase (following days after ET) are also related with the chances of ongoing pregnancy.ObjectiveTo evaluate the luteal phase endocrine profile through measurements of serum progesterone and estradiol on days ET+4, ET+7 and ET+11, to test their predictive value in relation to pregnancy outcome.SettingPrivate infertility center, Valencia, Spain.Materials and MethodsProspective cohort study performed between June 2017 and August 2018. Eligible patients were aged between 18-42 years, with a normal uterus, and being transferred 1-2 good quality blastocysts in a frozen ET cycle after an artificial endometrial preparation with estradiol valerate and vaginal micronized progesterone (400 mg/12 hours).ResultsA total of 127 patients were included. Mean age = 38.0 ± 3.9 years; BMI = 23.6 ± 3.6 kg/m2; endometrial thickness = 9.1 ± 1.6mm. Overall ongoing pregnancy rate = 47.2% (95%CI:38.3-56.3). Significantly higher levels of serum progesterone were observed on ET+4 (13.6 ± 6.0 vs. 11.1 ± 4.6ng/ml, p = 0.03) and ET+11 (15.7 ± 1.2 vs. 10.3 ± 0.6ng/ml, respectively; p = 0.000) in ongoing pregnancies versus negative β-hCG (β-human chorionic gonadotrophin) cases. On ET+7, ongoing pregnancies also had higher serum progesterone levels (14.2 ± 0.9 vs. 11.7 ± 0.8ng/ml, but did not reach statistical significance (p = 0.07). Serum estradiol levels were not related with pregnancy outcome at any moment of the luteal phase (p > 0.05). On days ET+4, +7 and +11, the ROC analysis showed that serum progesterone levels were predictive of ongoing pregnancy, and Pearson’s coefficient showed a significant association (p<0.05) of serum β-hCG levels with serum progesterone.ConclusionsIn hormonal replacement therapy cycles, serum progesterone levels across luteal phase days are associated with pregnancy outcome. Ongoing pregnancies were associated with a higher exposure to progesterone in comparison with pregnancy losses or negative β-hCG. Therefore, serum progesterone might be playing an important role not only during implantation, but also in pregnancy maintenance. It remains unknown if the variability in serum progesterone levels among patients, after receiving the exact same progesterone dose for luteal phase support, is the cause or just a consequence of pregnancy results.

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“…Improvement in and individualization of COS regimens have been the subject of intensive research in the field of ART, and patient-tailored COS has now become the state of the art. In contrast, the luteal phase of fresh IVF cycles has received little attention, and studies focusing on luteal phase characteristics following hCG triggering are scarce and have yielded conflicting results [56][57][58][59]. Neither the updated Cochrane meta-analysis on LPS [7], nor the ESHRE guidelines [6] have included recommendations regarding patient monitoring during the luteal phase.…”

Section: Personalized Luteal Phase Supportmentioning

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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Luteal phase progesterone and oestradiol after ovarian stimulation: relation to response and prediction of pregnancy

Cited by 17 publications

References 27 publications

The impact of preovulatory versus midluteal serum progesterone level on live birth rates during fresh embryo transfer

The impact of preovulatory versus midluteal serum progesterone level on live birth rates during fresh embryo transfer

Serum Progesterone Profile Across the Mid and Late Luteal Phase in Artificial Cycles Is Associated With Pregnancy Outcome

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

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