Serum Progesterone Levels Research Articles

FSHB and FSHR genes variants in combination with hormones levels predict low and high ovarian response to controlled ovarian stimulation: a logistic regressive model

BackgroundPredicting the number of follicles obtained after controlled ovarian stimulation (COS) is challenging, especially considering individual variability. Since FSH is a fundamental hormone that controls growing follicle activity, genetic variants are predicted to affect ovarian response to stimulation.The aim of the studyThe purpose of this study was to analyze whether FSHB rs10835638 and FSHR rs6166 genetic variants in combination with clinical parameters might be considered as potential precise predictors of ovarian response during COS.Materials and methodsThe present study included 144 women from infertile couples who underwent assisted reproductive technologies. Women with reduced FSH and/or AMH serum levels were excluded from the study. Genotyping was carried out applying restriction fragment length polymorphism analysis.ResultsGenotypes frequencies for FSHB rs10835638 and FSHR rs6166 were GG (73%), GT (24%), TT (3%) and AA (42%), AG (39%), GG (19%), respectively. FSHR rs6166 GG genotype was shown as associated with higher early follicular phase serum FSH, LH and progesterone levels, compared to AA and AG genotypes. Logistic regressive models that simultaneously use the patient’s genetic and clinical characteristics to calculate the probability of low or high ovarian response have been developed.ConclusionThe present study suggests that rs10835638 and rs6166 genetic variants affect hypothalamic-pituitary–gonadal hormones serum levels, and together may provide an improved model for predicting an ovarian response during COS.

Impact of progesterone concentration on hCG trigger day on clinical outcomes with cleavage-stage embryo transfer in in vitro fertilization cycles with an antagonist protocol

Objective: To investigate the impact of the progesterone concentration on human chorionic gonadotropin (hCG) trigger day in fresh cycles versus thawed transfer cycles (the freeze-all strategy) with an antagonist protocol, and to compare the differences in clinical outcomes. Methods: This retrospective cohort study included a total of 2 165 cycles conducted at Henan Provincial People's Hospital with cleavage-stage embryo (at least one top-quality) transfer between January 2017 and December 2023, with serum progesterone levels on hCG trigger day all≤6.34 nmol/L (i.e. 2 ng/ml). Multivariate logsitic regression analysis and curve fitting were performed based on different serum progesterone levels on hCG trigger day [≤3.17 nmol/L (i.e. 1 ng/ml) or 1-2 ng/ml]. Results: Multivariate regression analysis, by using cycle type (either fresh or frozen-thawed cycle) as the exposure variable, showed that the clinical pregnancy rate (≤1 ng/ml: OR=0.93, 95%CI: 0.75-1.14; 1-2 ng/ml: OR=1.05, 95%CI: 0.58-1.87) and live birth rate (≤1 ng/ml: OR=0.90, 95%CI: 0.71-1.13; 1-2 ng/ml: OR=1.53, 95%CI: 0.79-3.00) had no statistically significant differences in group of progesterone concentration ≤1 ng/ml or in group of 1-2 ng/ml. Using serum progesterone levels on hCG trigger day as a continuous variable for curve fitting analysis, the clinical pregnancy rate in fresh or thawed cycles showed no significant changes with increasing progesterone levels. Conclusions: In the antagonist protocol with cleavage-stage embryo transfer (at least one top-quality), when the serum progesterone level on hCG day is ≤2 ng/ml, there are no significant differences in clinical outcomes between thawed cycles and fresh cycles, including clinical pregnancy rate and live birth rate. Transferred in fresh cycles or choosing the freeze-all strategy could be selected based on the actual situation of the patients.

Dan'e fukang decoction reduces hemorrhage in a rat model of mifepristone induced incomplete abortion and may correlate with cell adhesion molecule signaling interference

Ethnopharmacological relevanceDan'e fukang decoction(DFD) is a traditional Chinese medicine formula. DFD obtains 10 herbs, including Salvia yunnanensis C.H.Wright (Zidanshen) , Curcuma zedoaria (Christm.) Roscoe (Ezhu), Angelica sinensis (Oliv.) Diels (Danggui), Cyperus rotundus L. (Xiangfuzi), Corydalis yanhusuo (Y.H.Chou & Chun C.Hsu) W.T.Wang ex Z.Y.Su & C.Y.Wu, Bupleurum marginatum Wall. ex DC. (Yanhusuo), Sparganium stoloniferum (Buch.-Ham. ex Graebn.) Buch.-Ham. ex Juz. (Sanleng), Panax notoginseng (Burkill) F.H.Chen (Sanqi), Paeonia lactiflora Pall. (Shaoyao) and Glycyrrhiza uralensis Fisch. (Gancao). DFD is now clinically used for the treatment of menstrual irregularities, dysmenorrhea and menstrual discomfort caused by blood stasis and easing of endometriosis. Based on this, it is reasonable to presume that DFD may be effective in treating incomplete abortion and reducing postpartum bleeding, but no specific studies have been reported so far. Aim of the studyTo investigate the efficacy of Dan'e fukang decoction (DFD) in reducing prolonged vaginal bleeding followed by mifepristone induced incomplete abortion and explore the mechanisms of action of DFD in treating incomplete abortion. MethodsAn incomplete abortion model of rat was established by single intragastrically administered 8.5 mg/kg mifepristone on the 7th day of pregnancy. From the 8th day of pregnancy, the abortive rats were administered solvent, a positive control drug, or different doses of DFD, respectively for seven consecutive days. The efficacy of DFD was assessed by measuring the vaginal bleeding volume of the rats. Four coagulation parameters and platelet counts were measured. Hematoxylin and eosin (HE) staining was performed to evaluate pathological changes in the uterine embryos. Serum levels of progesterone and estrogen were measured using ELISA. Network pharmacology and transcriptomics were used to predict potential targets and pathways for DFD to reduce hemorrhage. The levels of mRNA related to cell adhesion molecules (CAMs) were detected by RT-qPCR. The levels of progesterone and estrogen receptors and the proteins associated with CAMs pathway in uterine tissues were detected by Western Blot. ResultsDFD significantly reduced the volume of vaginal bleeding of the abortive rats and significantly downgraded the pathological scores of uterine embryos. DFD significantly increased serum levels of E2, and had no impact on serum levels of P4 and the protein expression of ER and PR in the uteri of the abortive rats. Pathways in cancer, lipid, focal adhesion and immune-related signaling were predicted to be influenced by DFD via the analysis of network pharmacology. The CAMs signaling was found the most critical pathway regulated by both mifepristone and DFD via RNA-seq assay, followed by axon guidance, basal cell carcinoma, hippo signaling pathway and neuroactive ligand-receptor interaction. Combining the two analytical methods, ICAM-1 was predicted likely the key targeted gene by DFD. Finally, DFD was validated to decrease the protein expression of ICAM-1, ITGB2, ITGB7 and RASSF5 in the uterine tissues, which correlated to suppress the CAMs signaling pathway. ConclusionDFD significantly reduced hemorrhage. DFD significantly increased the serum levels of E2 and inhibited CAMs signaling pathway, which was likely to be involved in the mechanism of action of DFD facilitating residual uterine embryo expulsion in the rat model of incomplete abortion.

Effect of Bypass Fat on Genital Status and Blood Biochemical Profiles in Pubertal Swamp Buffalo Heifers and Puerperal Swamp Buffalo Cows

Background: The interaction between nutrition and reproduction has long been known to have important implications for the reproductive performance in animal.The present study highlights the effect of by-pass fat supplementation on genital changes and blood biochemical profile in pubertal swamp buffalo heifers and puerperal swamp buffalo cows. Methods: 24 heifers of 2-2.5 years of age and 24 puerperal cows on the day of parturition, irrespective of parity were used as experimental animal. The analytical method was based on the treatment protocols of 3 groups in both heifers and cows (n=8 in each group) viz., treated with oral bypass fat alone (I), oral bypass fat, mineral mixtures and injectable phosphorus (II) and control (III) respectively. Genital status, metabolic hormone (leptin, Ghrelin and IGF-1), reproductive hormone (estrogen and progesterone) and mineral constituents (calcium, phosphorus, zinc and copper) were analyzed on day 0, day 15 and day 30 in heifers and day 15, day 30 and day 45 in cows respectively. Result: Feeding of bypass fat alone or bypass fat fortified with minerals and injectable phosphorus was not found to induce significant genital changes in heifers and cows. The serum leptin and IGF-1 levels were increased significantly (p less than 0.05) in heifers at day 30 in Group I and II. However, a significant rise (p less than 0.05) of leptin was recorded at day 45 in group I and II cows. IG1-1 level was recorded increased significantly only in cows treated with fortified bypass fat (Group II). With the progression of treatment the serum phosphorus level was increased significantly (p less than 0.05) in Group I and II cows. Serum estrogen levels were increased in both heifers and cows with progression of treatment in both Group I and II. However, serum progesterone levels were increased significantly only in heifers of Group I and II with progression of treatment.

Higher serum progesterone level has no negative impact on live birth rate in frozen embryo transfer

Optimal synchronisation between the endometrium and the embryo is key to the success of frozen embryo transfers (FET). It is achieved by administering different doses of exogenous oestrogen and progesterone (P4). The negative impact of low levels of P4 on FET has been reported, but there is a lack of knowledge about which levels are most appropriate. We aimed to evaluate whether high serum P4 levels measured on FET day affect the probability of having a baby at home. This retrospective cohort study includes 7546 FET cycles performed with hormone replacement therapy (HRT) for artificial endometrial preparation. Patients were divided into three groups according to P level on FET day (ng/mL): P4 < 20(n = 6623), P4 ≥ 20–40 (n = 770) and P > 40 (n = 146). Female age was per group P4 < 20 = 38.7 ± 3.1, P ≥ 20–40 = 39.0 ± 3.0, and P4 > 40 = 38.1 ± 2.9 years old (p = 0.53). The group with the highest progesterone levels found lower ongoing pregnancy rates without statistical significance (56.3 % (P4 < 20) vs 56.8 % (P4 ≥ 20-<40) vs 51.4 % (P4 > 40); p = 0.5). Miscarriage rate was also higher, although not significantly: 16.2 % (P4 < 20) vs 15.0 % (P4 ≥ 20-<40) vs 18.0 % (P4 > 40) (p = 0.6). These findings were explored with an adjusted analysis. A higher, but not significant, odds of miscarriage was observed when P4 > 40 ng/ml, aOR = 1.14 (0.75–1.74) (p = 0.55) whereas no such association was found with P4 ≥ 20–40 ng/ml (aOR = 0.92 (0.74–1.15) (p = 0.46)). The probability of livebirth is similar when the patient was P4 > 40 (aOR = 0.77 (0.51–1.15) (p = 0.20)) than when P4 ≥ 20-<40 (aOR = 0.94 (0.79–1.11) (p = 0.47). In conclusion, women with elevated serum P4 levels on the day of FET after HRT do not find their probability of live birth impaired.

Type 1 diabetes mellitus; ovarian reserve; anti-Müllerian hormone; ovarian function

BACKGROUND: Prolonged course of diabetes mellitus often leads to the development of vascular complications, insufficiency of ovarian function. The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus) it can have various adverse consequences for the mother, fetus, child and the course of pregnancy. Pregnancy planning in women with pregestational diabetes significantly improves the outcomes of pregnancy and childbirth. AIM: The aim of this study was to analyze gonadotropic and ovarian function parameters in patients with type 1 diabetes mellitus depending on the age of onset, duration and compensation level of the disease. MATERIALS AND METHODS: The patients included into this clinical prospective study were divided into two groups. The main group consisted of 216 patients with type 1 diabetes mellitus aged 18 to 39 years (mean age: 27.1 ± 3.1 years). The control group consisted of 30 healthy women of reproductive age. Chemiluminescent immunoassay was used to determine blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, free testosterone, and sex hormone-binding globulin from day 2 to day 5 of the menstrual cycle. Serum progesterone levels were measured on days 20–23 of the menstrual cycle for three consecutive cycles. Glycated hemoglobin levels were also studied in the blood serum of patients with type 1 diabetes mellitus. All the patients underwent pelvic ultrasound examination to assess the cohort of antral follicles and ovarian volume. RESULTS: The average age of menarche in patients with type 1 diabetes mellitus who developed the disease at the age of under 10 years was 14.2 ± 1.2 years. This was higher than in the group of girls with the onset of the disease over the age of 10 years (13.5 ± 1.2 years) and in women of the control group (11.9 ± 1.1 years). When assessing the ovarian reserve in patients with type 1 diabetes mellitus, we found a decrease in anti-Müllerian hormone level and antral follicle count in the group of women with disease onset at the age of under 10 years. We did not find differences in the ovarian reserve parameters in patients depending on disease duration. Normogonadotropic normoprolactinemic ovarian insufficiency was detected in 154 (71.3%) of 216 patients, while the rest 62 (28.7%) women had an ovulatory menstrual cycle. In patients with anovulation, luteal phase deficiency and ovulatory menstrual cycle, we found no differences between the age of development of type 1 diabetes mellitus, its duration, glycated hemoglobin levels, total daily insulin dose and insulin dose per kilogram of body mass. In patients receiving intensive insulin therapy with continuous subcutaneous insulin infusion, glycated hemoglobin level was lower than in those receiving multiple dose insulin injection therapy. CONCLUSIONS: The average age of menarche in patients with type 1 diabetes mellitus is higher than in healthy women. The ovarian reserve parameters in patients with early onset of the disease, before 10 years of age, are lower than in patients who developed type 1 diabetes mellitus after 10 years of age. Duration of pregnancy planning period depends on compensation level of the disease and lasts from six to 12 months. This requires the doctor and patient to prepare for the implementation of reproductive tasks as early as possible, especially in patients whose disease onset occurred in pre-pubertal period.

NAGK Regulates the Onset of Puberty in Female Mice

This study examines the role of N-acetylglucosamine kinase (NAGK) in initiating puberty in female mice. We employed real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunofluorescence to measure NAGK expression in the hypothalamic-pituitary-ovarian axis across various developmental stages: infant, prepuberty, puberty, and adult. We further investigated the impact of Nagk gene knockdown on puberty in female mice. This included assessing the expression of puberty-related genes both in vivo and in vitro, GT1-7 cells proliferation and apoptosis, concentrations of GnRH and Kisspeptin, puberty onset timing, serum levels of progesterone (P4) and estradiol (E2), and ovarian morphology. Results revealed that Nagk mRNA is present in the hypothalamus, pituitary, and ovaries throughout different developmental stages in female mice. In the hypothalamus, Nagk mRNA levels were comparable during infant and prepuberty, lowest during puberty, and highest in adult. In the pituitary, Nagk mRNA peaked in adult, with no significant variation between infant, prepuberty, and puberty. In the ovaries, Nagk mRNA levels increased during puberty and peaked in adult. NAGK is predominantly located in the arcuate nucleus (ARC), periventricular nucleus (PeN), dorsomedial hypothalamic nucleus (DMH), paraventricular nucleus (PVN), adenohypophysis, and in the ovarian oocytes, interstitium, and granulosa cells across all developmental stages in female mice. Nagk knockdown in GT1-7 cells decreased the transcriptional level of Gnrh, Kiss1, Gpr54, Igf1 and Mapk14 mRNA and cell proliferation but increased the level of β-catenin mRNA and cell apoptosis, while reducing GnRH secretion. Following ICV injection, Nagk gene knockdown mice exhibited delayed the timing of vaginal opening (VO) and reduced hypothalamic levels of Gnrh, Kiss1, Gpr54, Igf1, Mapk14, and β-catenin mRNA. Additionally, serum concentrations of E2 in Nagk gene knockdown mice were significantly lower compared to the control group. These findings indicate that Nagk regulates the expression of Gnrh and Kiss1 mRNA in GT1-7 cells, affects hypothalamus Gnrh mRNA levels and serum E2 concentration, and that its knockdown can delay puberty onset in female mice.

Evaluation of the Contraceptive Effect of Aqueous Extract of Unripe Fruit of Musa paradisiaca Linn. (Musaceae) in Female Rats.

Musa paradisiaca (plantain) is a tropical staple food known for its rich nutrient content and bioactive compounds. Traditionally, the unripe plantain has been utilized in folk medicine to treat various conditions, such as digestive disorders, inflammation, and infections. This study aimed to evaluate the potential contraceptive effects of the aqueous extract of unripe Musa paradisiaca (Musaceae) in female rats. The aqueous extract was obtained through maceration of the plant material in distilled water. Experimental animals were divided into four groups (n=6 per group): Groups A, B, and C received 100, 200, and 400 mg/kg of the extract, respectively, while Group D served as the control. A 21-day oral administration of the extract was conducted to assess its impact on reproductive hormones, with weekly blood samples collected to measure serum estrogen, prolactin, and progesterone levels via enzyme-linked immunosorbent assay (ELISA). The results demonstrated a significant (p &lt; 0.05) alteration in estrogen levels across all extract-treated groups. There was a dose-dependent significant reduction (p &lt; 0.05) in prolactin and progesterone levels in the groups treated with 200 and 400 mg/kg at week 2 and week 3. These findings indicate that while lower doses of the aqueous extract had no discernible effect on reproductive hormone levels, higher doses significantly reduced prolactin and progesterone, suggesting the extract's potential as a contraceptive agent.

Differential diagnosis of non-molar gestational trophoblastic neoplasia with ectopic pregnancy by clinical-pathological features.

This study was presented to investigate the clinical-pathological characteristics of gestational trophoblastic neoplasia (GTN) following non-molar pregnancy and differentiated with ectopic pregnancy (EP). The clinical data of 83 patients who were admitted for suspected GTN after non-molar pregnancy at the Women's Hospital School of Medicine Zhejiang University from January 2015 to September 2022 were selected for analysis. In total, 41 cases were confirmed non-molar GTN, including 31 choriocarcinoma, 9 PSTT (placental site trophoblastic tumor), and 1 ETT (epithelioid trophoblastic tumor), while 42 cases were confirmed EP. Compared with ectopic pregnancy, non-molar GTN patients had lower levels of serum progesterone compared with EP (3.81nmol/L vs 17.70nmol/L, P = 0.001). Based on the ultrasound, the thickness of the endometrium was thinner in patients with non-molar GTN compared with EP (0.565cm vs 0.70cm, P = 0.018). By histopathologic examination, the endothelium of non-molar GTN showed less decidual-like changes compared with EP (64.3% vs 14.6%, P = 0.001). A combination of serum progesterone levels, endometrium thickness, and histopathologic features of the endometrium can help to differentiate non-molar GTN and EP. Surgeries including hysteroscopy with curettage and/or laparoscopy are needed.

Chenodeoxycholic acid fortified diet drives ovarian steroidogenesis to improve embryo implantation through enhancing uterine receptivity via progesterone receptor signaling pathway in rats

Infertility is a worldwide reproductive health problem influenced by the embryo implantation efficiency. We previously revealed that dietary chenodeoxycholic acid (CDCA) positively influence the early embryo implantation. But how CDCA regulate embryo implantation is largely unexplored. Herein, we investigated the mechanism behind CDCA's regulation on embryo implantation in rats. Results showed that CDCA promoted uterine receptivity, leading to increased number of implantation sites. Mechanistically, CDCA reshaped maternal amino acid metabolism and enhanced serum progesterone levels. CDCA enhanced ovarian progesterone synthesis by improving steroidogenesis-related protein (StAR and CYP11A1) expression via Takeda G-protein-coupled receptor 5. Elevated progesterone exaggerated uterine progesterone but weakened the estradiol signaling in the CDCA group, contributing to better uterine receptive for embryo implantation. Additionally, elevated transcription repressor Stat5b induced the down-regulation of progesterone-metabolizing enzyme 20-hydroxysteroid dehydrogenase 20α-HSD, complementally explained uterine progesterone signaling enhancement. Overall, our data revealed that CDCA drove ovarian steroidogenesis to improve embryo implantation through enhancing uterine receptivity via progesterone receptor pathway in rats. Therefore, CDCA diet may be a potential favorable nutritional strategy for infertility and pregnancy management.

The Effects of L-Tartaric Acid on Ovarian Histostereological and Serum Hormonal Analysis in an Animal Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine-related reproductive disorder in women of reproductive age, accompanied by both the impairment of female fecundity and a risk of metabolic disorders. PCOS is emphasized as a worldwide concern due to its unknown etiology and lack of specific medications. The current study aimed to evaluate the effects of L-tartaric acid, an abundantly occurring compound in fruits, on the histostereological and hormonal changes caused by PCOS. Forty adult Sprague Dawley rats were randomly divided into four groups including controls (no intervention), Tartaric acid (40mg/Kg/day from day 21 onwards for 39 days), PCOS (21 days letrozole and then normal saline orally for 39 days), and PCOS + Tartaric acid. After treatments, the ovarian histostereological analysis as well as the level of reproductive hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone, and testosterone was measured. PCOS caused a significant decrease in the number of unilaminar, multilaminar, antral, and graafian follicles and increased follicular atresia (p-value < 0.001). Moreover, the weight and volume of ovarian tissue and related structures including cortex, medulla, and cysts increased significantly (p-value < 0.0001). However, corpus luteum volume was significantly decreased (p-value < 0.001). Although significant differences were found in some parameters with the control group (p-value < 0.05), the administration of tartaric acid restored the pathological effects of PCOS on the ovarian histostructure. Furthermore, tartaric acid improved the serum levels of LH, estradiol, progesterone, and testosterone (p-value < 0.05). The obtained findings may suggest tartaric acid as a novel strategy for PCOS management, although further studies are necessary.

Anti-implantation and uterotonic properties of Mentha pulegium L. in female Sprague-Dawley rats

Background: Some traditional herbs disrupt endocrine-endometrial synchrony, affecting embryo-endometrium communication during fertility. Hormonal imbalances cause non-receptive conditions, leading to anti-implantation or abortion. Historically, Mentha pulegium has served for contraceptive and abortive purposes. Its effects on the post-coital contraceptive and hormonal activities were evaluated. Methods: Thirty-six Sprague-Dawley female rats were selected based on the presence of copulation plugs and received 200, 500, and 1000 mg/kg of Hydroethanolic leaf extract of Mentha pulegium L. (MPE) for seven days. Reproductive organ weights and serum estrogen and progesterone levels were measured. The resorption index, anti-implantation activity, and pre-implantation loss were also calculated using the number of implantation sites and resorptions in all treatments. Data were presented as mean±standard error mean (SEM), and significance was defined as p&lt;0.05 using one-way ANOVA. Results: Post-coital administration of MPE resulted in resorptive, pre-implantation loss, and anti-implantation activity. A dose of 200 mg/kg reduced the number of implantations and exhibited a high resorption index, percentage pre-implantation loss, and anti-implantation activity. A marked decline in serum progesterone levels and a significant reduction in serum estrogen and progesterone ratio was observed at 200 mg/kg MPE. A significant increase in uterine weight was observed in the 500 mg/kg treatment. Doses of 500 and 1000 mg/kg resulted in a significant reduction in anti-implantation activity. Conclusions: The observed anti-implantation activity and pre-implantation loss suggest the abortifacient properties of MPE. However, its effects were seen to be dose-dependent.

Hydro-Ethanol Extracts of Xylopia aethiopica Enhanced Serum Testosterone Levels in Male Adult Wistar Rats

Objectives To investigate the effects of hydro-ethanolic extracts of leaves and fruit with or without seeds on male sex hormones. Material and Methods Hydro-ethanolic extracts of the leaves, fruits with seeds, and fruits without seeds were processed using the Soxhlet extraction technique. Wistar rats were administered 125, 250, and 500 mg/kg of the extracts by oral gavage for 30, 60, and 90 days while the control group received feeds and water ad libitum. After the treatment periods, rats were sacrificed by cervical dislocation, and blood was collected by cardiac puncture. Serum follicle-stimulating hormones (FSHs), luteinising hormone (LH), progesterone, prolactin, and testosterone levels were determined using an enzyme-linked immunosorbent assay technique. Data were compared using analysis of variance (ANOVA), and a p-value of 0.05 was considered significant. Results Serum testosterone, FSH, and LH levels in rats treated with 125, 250, and 500 mg/kg were significantly increased (p &lt; 0.05) in a dose-dependent manner compared with controls. Conclusion The consumption of this commonly used food spice appears to have beneficial effects on the male sex hormones.

Ovulation Induction Response in Non-Obese Versus Obese Women with Polycystic Ovarian Syndrome at Fertility Clinic of a Tertiary Care Hospital, Rawalpindi

Background: More than 80% of premenopausal females presenting with Polycystic Ovarian Syndrome (PCOS) have above average BMI. Obesity enhances the magnitude of hormonal and metabolic disturbances leading to anovulation. Objective: To validate the influence of obesity on response of ovulation induction by Clomiphene citrate in PCOS related subfertility. Methodology; Study Design &amp; Setting: Comparative Analytical study at Fertility Clinic of Department of Obstet &amp; Gynae, Benazir Bhutto Hospital, Rawalpindi. Study Duration: Twelve months (Dec 2020-Dec 2021) Method: Rotterdam criteria was used to diagnose PCOS. WHO criteria of BMI=23 kg/m² cutoffs for Asian population was used to divide women in two groups; non-obese (Group-A &lt; 23 kg/m²) and obese/overweight (Group-B ≥ 23 kg/m²). In both groups ovulation was induced with Clomiphene Citrate and response was assessed via ultrasound follicular tracking, Day 21 serum progesterone and serum B-HCG levels two weeks after the HCG injection. Results: Total participants were 200 (100 in each group). Mean age (years) in Group-A vs Group-B was 25.38 vs, 27.62 and mean BMI (kg/m²) was 20.82 vs 28.34 respectively. The frequent symptoms in Group-A Vs Group-B were Oligomenorrhoea (87% vs 97%) and amenorrhoea (13% vs 03%). P-value (0.009) was significant. Difference in Ultrasound features of PCOS and LH:FSH ratio in both groups were insignificant (P-value=0.214 and 0.316 respectively). The difference in almost all parameters of OI between the two groups was statistically significant. In Group-A vs Group-B; the presence of dominant follicle after Clomiphene citrate was 52% vs 34% (p value=0.01); Day 21 serum progesterone &gt;30ng/ml was 21% vs 09% (p value=0.01); a positive serum β-HCG level &gt;50 mIU/L 02 weeks after HCG administration was 12% vs 04% (p value=0.09). Conclusion: Obesity control and lifestyle modification are imperative for significant improvement in fertility outcomes for PCOS related subfertility.

High serum progesterone levels on the day of embryo transfer in patients undergoing artificial frozen-thawed blastocyst transfer: Is there a ceiling effect?

To evaluate the potential ceiling effect of high serum progesterone levels on the day of embryo transfer for pregnancy outcomes in patients undergoing artificial frozen-thawed blastocyst transfer (FET) cycles. This retrospective cohort study included 595 patients who underwent artificial FET cycles. We evaluated progesterone levels and found that 40.6 ng/mL corresponded to the 90th percentile and 23.9 ng/mL corresponded to the 50th percentile. Based on these findings, we categorized progesterone levels as <20 ng/mL (n=220, 37.0%), 20-40 ng/mL (n=312, 52.4%), and ≥40 ng/mL (n=63, 10.6%). The primary outcome measures were the clinical pregnancy rate (CPR) and live birth rate (LBR). Blastocyst morphology grades, including expansion, trophectoderm, and inner cell mass grades, were significantly associated with clinical pregnancy (p<0.001 for all). Progesterone levels between 20 and 40 ng/mL were associated with higher CPR (p=0.043). In the multivariate analysis, only blastocyst expansion and inner cell mass grades were independently and significantly associated with CPR [p=0.011, odds ratio (OR)=1.6, (confidence interval) CI 95%=1.13-2.39, and p=0.007, OR=1.65, CI 95%=1.14-2.39, respectively]. The progesterone level and trophectoderm grade were not statistically significant. Regarding LBR, only blastocyst expansion grades 4 and trophectoderm grades A or B were significantly associated. Based on these data, we speculate that if serum progesterone levels exceed 40 ng/mL on the day of embryo transfer in patients undergoing artificial FET cycles, there is no need to reduce the progesterone dose.

Impact of polyamine supplementation on GnRH expression, folliculogenesis, and puberty onset in young mice

BackgroundThe hypothalamic-pituitary-gonadal (HPG) axis is pivotal in regulating reproductive functions, with gonadotropin-releasing hormone (GnRH) acting as a central regulator. Recently, polyamines have been shown to regulate the HPG axis, including GnRH expression and ovarian biology in old and adult rodents. The present study firstly highlights the age-specific variation in the polyamine and their corresponding biosynthetic enzymes in the ovary during aging, and further, the study focuses on the effect of polyamines, putrescine, and agmatine, in young female mice. Method and resultImmunofluorescence analysis revealed age-related differences in the expression of ornithine decarboxylase 1 (ODC1), spermine (SPM), and spermidine (SPD) in the ovaries, with adult mice exhibiting significantly higher expression levels compared to young and old mice. Likewise, qPCR analysis showed the mRNA levels of Odc1, Spermidine synthase (Srm), and Spermine synthase (Sms) show a significant increase in adult ovaries, which is then followed by a significant decline in old age. Histological examination demonstrated morphological alterations in the ovaries with age, including decreased follicle numbers and increased stromal cells in old mice. Furthermore, treatment with putrescine, a polyamine, in young mice resulted in larger ovaries and increased follicle numbers compared to controls. Additionally, serum levels of gonadotropin-releasing hormone (GnRH) and progesterone (P4) were measured, showing elevated levels in polyamine-treated mice. GnRH mRNA expression also increased significantly. Gene expression analysis revealed upregulation of genes associated with folliculogenesis such as Fshr, Bmp15, Gdf9, Amh, Star, Hsdb3, and Plaur in the ovaries and onset of puberty such as Tac2, and Kiss1, and a decrease in Mkrn3 in the hypothalamus of polyamine-treated mice. ConclusionThis study investigates the effect of polyamines in young immature female mice, shedding light on their role in upregulating GnRH, and enhancing folliculogenesis. Overall, these findings suggest that polyamines play a crucial role in ovarian aging and HPG axis regulation, offering potential therapeutics to reinstate fertility in reproductively challenged individuals.

Preovulatory progesterone levels are the top indicator for ovulation prediction based on machine learning model evaluation: a retrospective study

BackgroundAccurately predicting ovulation timing is critical for women undergoing natural cycle-frozen embryo transfer. However, the precise predicting of the ovulation timing remains challenging due to the lack of consensus among different clinics regarding the definition of this significant event.ObjectiveTo compare the effectiveness of preovulatory serum progesterone levels (P4) versus luteinizing hormone levels (LH) in predicting ovulation time using two machine learning models.Methods771 patients who underwent autologous natural cycle-frozen embryo transfer between January 2015 and February 2022 were recruited. Utilizing variables including follicle diameters, preovulatory serum levels of LH, E2, and P4, two machine learning models were constructed to predict the ovulation time, the importance of the variables in predicting ovulation timing was further ranked.ResultsTwo machine learning models have the capability to accurately predict the timing of ovulation, specifically within 72, 48, or 24 h. The overall accuracy rates of the validation dataset, as determined by the classification trees and random forest models, were found to be 78.83% and 85.28% respectively. Notably, when predicting ovulation within 24 h, the accuracy rate of P4 ≥ 0.65ng/ml exceeded 92%. Furthermore, it was important to consider LH or E2 levels in conjunction with P4 when assessing ovulation timing in cases where P4<0.65ng/ml.ConclusionsPreovulatory serum P4 levels are better predictors of ovulation timing than LH levels and could be used as an alternative in clinical settings, and the model we developed can be used to pinpoint the day of ovulation. Ongoing research and advancements in technology are anticipated to enhance and refine the ovulation method.

Measuring The Level of The Hormone Progesterone on The Day of Transfer of Fresh and Frozen Embryos and Its Impact on Pregnancy Outcomes

Objective: Prediction of the effect of the hormone progesterone on pregnancy results that measured on the day of transfer of fresh and frozen embryos. Method: This research at reproductive centres in Baghdad from May 2022 to April 2023 examined how serum progesterone levels affect embryo transfers in ICSI procedures in 100 fresh or frozen cycle women. The study examined clinical data and endometrial preparation techniques to determine if progesterone levels affect pregnancy rates. Data were analysed using SPSS to determine how pre-transfer hormonal levels affected implantation and pregnancy outcomes. Participants were selected according on inclusion and exclusion criteria. The study shows that progesterone is essential for IVF embryo transfers. Results: Compared to frozen cycles in females, fresh cycles had greater mean age and progesterone levels but lower COC number and 2PN levels, with no changes in BMI, MII, or injectable MII. Frozen cycles produced more good-grade embryos, whereas fresh cycles produced more fair-grade embryos. There were no differences in the number of "C" embryos. Fresh cycle groups had greater pregnancy rates (59.1%) than frozen cycle groups (38.9%), but progesterone levels did not change between cycle types. Conclusion: The study found that fresh cycles include older participants, greater progesterone but lower COC and 2PN levels, and higher pregnancy rates than frozen cycles. BMI, MII levels, embryo count, poor grade "C" embryos, and progesterone levels associated to pregnancy outcomes did not differ across groups.

Alterations in the Hypothalamic-Pituitary-Adrenal Axis as a Response to Experimental Autoimmune Encephalomyelitis in Dark Agouti Rats of Both Sexes.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.

Luteinizing Hormone Receptor Mutation (LHRN316S) Causes Abnormal Follicular Development Revealed by Follicle Single-Cell Analysis and CRISPR/Cas9

Abnormal interaction between granulosa cells and oocytes causes disordered development of ovarian follicles. However, the interactions between oocytes and cumulus granulosa cells (CGs), oocytes and mural granulosa cells (MGs), and CGs and MGs remain to be fully explored. Using single-cell RNA-sequencing (scRNA-seq), we determined the transcriptional profiles of oocytes, CGs and MGs in antral follicles. Analysis of scRNA-seq data revealed that CGs may regulate follicular development through the BMP15-KITL-KIT-PI3K-ARF6 pathway with elevated expression of luteinizing hormone receptor (LHR). Because internalization of the LHR is regulated by Arf6, we constructed LHRN316S mice by CRISPR/Cas9 to further explore mechanisms of follicular development and novel treatment strategies for female infertility. Ovaries of LHRN316S mice exhibited reduced numbers of corpora lutea and ovulation. The LHRN316S mice had a reduced rate of oocyte maturation in vitro and decreased serum progesterone levels. Mating LHRN316S female mice with ICR wild type male mice revealed that the infertility rate of LHRN316S mice was 21.4% (3/14). Litter sizes from LHRN316S mice were smaller than those from control wild type female mice. The oocytes from LHRN316S mice had an increased rate of maturation in vitro after progesterone administration in vitro. Furthermore, progesterone treated LHRN316S mice produced offspring numbers per litter equivalent to WT mice. These findings provide key insights into cellular interactions in ovarian follicles and provide important clues for infertility treatment.Graphical