Center for Human Reproduction-Institut Francophone de Recherche Et d'études Appliquées à la Reproduction Et Sexologie (IFREARES), Clinique Saint Jean du Languedoc, Toulouse, France.
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.
PMID 35757393 35757393 DOI 10.3389/fendo.2022.892753 10.3389/fendo.2022.892753
Cite this article
Ranisavljevic, N., HUBERLANT, S., Montagut, M., Alonzo, P., Darné, B., Languille, S., Anahory T, & Cédrin‐Durnerin, I. (2022). Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses. Frontiers in endocrinology, 13, 892753. https://doi.org/10.3389/fendo.2022.892753
Ranisavljevic N, HUBERLANT S, Montagut M, Alonzo P, Darné B, Languille S, et al. Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses. Front Endocrinol (Lausanne). 2022;13:892753. doi:10.3389/fendo.2022.892753
Ranisavljevic, Noemie, et al. "Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses." Frontiers in endocrinology, vol. 13, 2022, pp. 892753.
To evaluate the clinical relevance of serum progesterone levels on the day of frozen embryo transfer (FET) and the dose of vaginal progesterone gel (Crinone) used for early luteal phase support (LPS) in artificial-cycle frozen embryo transfer (AC-FET). This single-center retrospective study analyzed 342 AC-FET cycles in patients aged 18-45 at Changhua Christian Hospital, Taiwan (April 2018-December 2022). Women aged 18-45 years undergoing AC-FET were included; cycles with >3 prior failed FETs, major comorbidities, donor oocytes, or missing outcome data were excluded. Pregnancy outcomes were assessed per cycle. Crinone (90 mg or 180 mg daily) was administered for 5 days after endometrial thickness ≥7 mm and progesterone <1.5 ng/mL. Serum progesterone was measured on the day of FET. Clinical pregnancy rates based on gestational sac (CPR-S), fetal heartbeat (CPR-H), and live birth rate (LBR) were evaluated. Receiver operating characteristic (ROC) evaluated the predictive value of serum progesterone levels. Associations between study variables and pregnancy outcomes were assessed using univariate and multivariable logistic regression. Comparisons of pregnancy outcomes between the high- and low-dose Crinone groups were further conducted using inverse probability of treatment weighting (IPTW) to adjust for baseline differences between dosage groups. Serum progesterone levels demonstrated poor predictive performance for CPR-S, CPR-H, and LBR (AUC 0.541-0.559) and were not independently associated with pregnancy outcomes in multivariable analyses. After adjustment using inverse probability of treatment weighting, a higher Crinone dose (180 mg vs. 90 mg) was significantly associated with higher CPR-S (OR, 1.87; 95% CI, 1.11-3.17; p = 0.020), CPR-H (OR, 2.11; 95% CI, 1.24-3.59; p = 0.006), and LBR (OR, 2.10; 95% CI, 1.31-3.38; p = 0.002). Serum progesterone levels measured on the day of FET did not predict pregnancy outcomes in AC-FET cycles using vaginal progesterone gel. A higher Crinone dose was associated with higher early clinical pregnancy rates compared with a lower dose.
Primary ovarian insufficiency (POI) is a common gynecological disease with serious ramifications including low pregnancy rate and low estrogen symptoms. Traditional Chinese medicine is regarded as an effective treatment for POI. However, the therapeutic mechanism of it is unclear. In this study, a mouse model of primary ovarian insufficiency was established by intraperitoneal injection of cyclophosphamide (CTX) and He's Yang Chao Recipe (HSYC) concentrate was used for intragastric administration. Serum hormone levels (Anti-Müllerian Hormone, Estradiol, Progesterone, Luteinizing Hormone and Follicle Stimulating Hormone) and Oxidative Stress (OS) related products, superoxide dismutase (SOD), GSH-Px, and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Pathological changes in ovarian tissue were evaluated by hematoxylin and eosin staining, and flow cytometry was used to determine reactive oxygen species content and mitochondrial membrane potential levels in granulosa cells. Mitochondrial distribution and morphology were investigated using immunofluorescence staining. The level of mitophagy was evaluated by LC3 immunofluorescence staining and autophagosome counts using electron microscopy. Western blotting and qPCR were used to detect the expression of proteins and genes related to mitophagy and the NLRP3 inflammasome. After HSYC treatment, the ovarian damage was milder than in the CTX group. Compared with the CTX group; SOD, GSH-Px, and the total antioxidant capacity were significantly increased, while MDA and ROS were decreased in the HSYC treatment groups. Furthermore, mitochondrial distribution and membrane potential levels were improved after HSYC treatment compared to the CTX group. After the HSYC treatment, the LC3 fluorescent intensity and autophagosome counts were decreased. Similarly, mitophagy related markers PINK1, Parkin, LC3, and Beclin1 were decreased, while p62 was significantly increased, compared with the CTX groups. The mRNA and protein expression of NLRP3 inflammasome, NLRP3, caspase-1, GSDMD, IL-18, and IL-1β were significantly decreased in the HSYC treatment groups. This is the first study in molecular mechanisms underlying HSYC against granulosa cell injury in POI. HSYC protects ovaries from CTX-induced ovarian damage and oxidative stress. HSYC enhanced ovarian function in mice with primary ovarian insufficiency by inhibiting PINK1-Parkin mitophagy and NLRP3 inflammasome activation.
Is there a difference in live birth rates at 24 months between infertile women with polycystic ovary syndrome (PCOS) who have normal versus abnormal glucose metabolism? Abnormal glucose metabolism did not significantly reduce live birth rates but was associated with increased obstetric complications. Women with PCOS are often at increased risk of glucose metabolism disorders. However, evidence about the impact of these disorders on pregnancy outcomes remains limited, particularly in Asian populations. This prospective cohort study was conducted at a reproductive care centre in Vietnam from June 2020 to August 2024. A total of 1208 women were enrolled. PARTICIPANTS/MATERIALS Eligible participants were infertile women aged 18-40 years diagnosed with PCOS (Rotterdam criteria). Comprehensive assessments included medical history, anthropometric measurements, endocrine evaluations, fasting plasma glucose (FPG), glycosylated haemoglobin (HbAlc), and oral glucose tolerance tests (OGTT). Participants were categorized into normal or abnormal glucose metabolism groups and monitored for live birth outcomes at 24 months from the first visit. MAIN Live birth rates at 24 months were comparable between women with normal versus abnormal glucose metabolism (52.7% vs 48.2%, P = 0.12). However, obstetric complications, including gestational diabetes mellitus (15.2% vs 28.0%, P < 0.001) and hypertensive disorders of pregnancy (2.3% vs 9.0%, P < 0.001), were more common in the group with abnormal glucose metabolism. In women who conceived naturally, greater waist circumference and higher Homeostatic Model Assessment of Insulin Resistance index were significantly associated with lower odds of live birth, whereas the presence of hyperandrogenism was associated with higher odds of live birth. No factors were significantly associated with live birth in the group that conceived via ovulation induction plus IUI. In the group that conceived through IVF or IVM, a higher BMI was significantly associated with a lower live birth rate. LIMITATIONS This single-centre study was conducted exclusively on infertile women from South-East Asia who had PCOS, potentially limiting generalizability to other populations. Additionally, metabolic assessments were only performed at baseline, preventing evaluation of longitudinal changes and their dynamic effects on reproductive outcomes. While no significant difference in live birth rates was observed between PCOS women with normal and abnormal glucose metabolism, the abnormal glucose metabolism group experienced higher rates of gestational complications. These findings underscore the importance of preconception metabolic screening and tailored fertility strategies that include targeted interventions to optimize reproductive and maternal outcomes in women with PCOS. This study was supported by My Duc Hospital. Lan N. Vuong reports funding from the Vietnam National Foundation for Science and Technology Development (NAFOSTED; grant number FWO.108-2022.01); Speaker and conference fees; speaker and conference fees as well as a grant; speaker, conference, and scientific board fees outside the submitted work. All other authors declare no conflicts of interest. NCT04364087.
Serum progesterone (P) levels are critical for endometrial receptivity and implantation in frozen-thawed embryo transfer (FET) cycles. However, the prognostic role of P levels measured on the day of the β-human chorionic gonadotropin (β-hCG) pregnancy test has not been fully elucidated. This study aimed to evaluate the association between β-hCG day serum P levels and pregnancy outcomes in FET cycles. This retrospective cohort study included 621 FET cycles performed between January 2023 and December 2024, of which 79.5% were conducted using hormone replacement therapy (HRT) protocols and 20.5% using natural cycle (NC) protocols. Serum P levels were measured on the day of the β-hCG pregnancy test. Receiver operating characteristic (ROC) curve analysis was used to determine protocol-specific P thresholds for predicting ongoing pregnancy (OPR). Ongoing pregnancy was defined as a viable intrauterine pregnancy confirmed by ultrasound at or beyond 12 weeks of gestation. Multivariable logistic regression was applied to identify independent predictors of OPR. ROC analysis identified optimal P thresholds of 15.5 ng/mL in NC cycles (AUC 0.821) and 14.15 ng/mL in HRT cycles (AUC 0.595). Overall, 44% of patients had serum P levels below the protocol-specific threshold. OPR was significantly higher in patients with P levels above the threshold (NC: 63.0% vs. 12.8%; 48.1% vs. 31.9%; p < 0.001). Multivariable regression demonstrated that younger maternal age and higher β-hCG day P levels independently predicted OPR. In HRT cycles, blastocyst-stage transfer was also significantly associated with improved outcomes (OR = 0.27, 95% CI 0.13-0.59; p < 0.05). Serum P levels measured on the day of the β-hCG test are significantly associated with pregnancy outcomes in both HRT and NC FET cycles. Routine monitoring of late luteal P levels and individualized luteal phase support strategies may enhance clinical success rates.