Gonadotropin Administration Research Articles

Cell Communications Between GCs and Macrophages Contribute to the Residence of Macrophage in Preovulatory Follicles.

There were not only granulosa cells (GCs) but also immune cells in preovulatory follicular fluid. The objective of this study was to explore the interactions between macrophages and GCs via adhesion molecules in preovulatory follicles and the regulatory mechanisms of the interactions. Flow cytometry and immunofluorescence were used to detect the expression of ITGB1 in macrophages and fibronectin (FN)1 in GCs in preovulatory follicles from 12 patients. The synthesis of FN1 protein in human ovarian GCs line (KGN) was detected by western blot. An adhesion experiment was performed to observe the changes of KGN cells adhesion to macrophages. The progesterone levels 12 h after human chorionic gonadotropin (HCG) administration in the high proportion immune cells (high immune [HI]) group were significantly higher than that in the low proportion immune cells (low immune [LI]) group (p < 0.0001). The expression of ITGB1 in macrophages in the HI group was higher than in the LI group. The expression of FN1 in GCs in HI group was higher than in LI group (p < 0.01). Progesterone increased the synthesis of FN1 in KGN cells (p < 0.0001) and was suppressed by the elimination of PGR. The adhesion effect of KGN cells on macrophages was enhanced by progesterone (p < 0.0001). After luteinizing hormone (LH)/HCG surge, progesterone promotes the expression of FN1 in GCs by acting on the receptor PGR, and then GCs enhance the adhesion of macrophages by FN1-ITGB1 interaction, further leading to the result that macrophages perform diverse functional activities to maintain tissue homeostasis during ovulation.

Clinical outcomes of round spermatid injection versus intra-cytoplasmic sperm injection: The potential role of hormonal pretreatment in male patients with non-obstructive azoospermia.

Round spermatid injection (ROSI) into oocytes offers men with non-obstructive azoospermia (NOA) the opportunity to have biological offspring in cases where mature spermatozoa are not detected. However, the clinical outcomes of ROSI remains poor. This study compares the outcomes of ROSI with intracytoplasmic sperm injection (ICSI) and investigates the effect of hormonal pretreatment. This retrospective cohort study enrolled infertile couples undergoing either ROSI or ICSI at the reproductive center in Taipei Veterans General Hospital. The administration of selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors in male patients were collected. Relevant hormonal markers and biochemical parameters were determined. The outcomes of ROSI and ICSI were assessed based on fertilization rate, implantation rate, and live birth rate. A total of 36 couples were recruited in the ROSI group, whereas 39 couples were recruited in the ICSI group for the analysis. Patients in each group demonstrated similar characteristics, except for a higher proportion of male patients in the ROSI group who were pretreated with anastrozole. The fertilization rate and implantation rate were similar between ROSI and ICSI groups after adjusting for confounding variable. The live birth rate was significant lower in the ROSI group (8.3%) than in the ICSI group (30.8%) before and after adjusting for confounding variable. ROSI demonstrated fertilization and implantation rates comparable to those of ICSI for male patient with NOA undergoing testicular sperm extraction surgery. Further studies evaluating the effect of anastrozole administration on ROSI outcomes are warrant.

Ongoing Clinical Trials for Polycystic Ovarian Syndrome (PCOS) Afflicted Infertility in Women: A Narrative Review.

Polycystic Ovary Syndrome (PCOS) is a highly prevalent endocrine disorder that affects women of reproductive age. PCOS is further correlated with infertility, menstrual dysfunction, and hyperandrogenism. Despite the advanced understanding of reproductive biology, the exact causes of PCOS remain ambiguous. Nevertheless, several factors are believed to contribute to the development of PCOS, including insulin resistance, hyperinsulinemia, obesity, and genetic predispositions. The diagnosis of PCOS is complicated by its phenotypic heterogeneity, which manifests differently in different individuals. Presently, the therapeutic management of PCOS-afflicted infertility depends upon proper pharmaceutical-based therapies aimed at treating underlying symptoms, such as the use of clomiphene citrate, metformin, ovulation-inducing agents, anti-androgens, exogenous gonadotropin administration, laparoscopic ovarian drilling, and in vitro fertilization. The present review focuses on narrating present therapeutic interventions along with lifestyle modifications in PCOS. Furthermore, it focuses on the ongoing clinical trials of various chemotherapeutics to counter PCOS-induced infertility among women.

Ameliorative Effect of Lycopene on Follicular Reserve Depletion, Oxidative Damage, Apoptosis Rate, and Hormonal Profile during Repeated Superovulations in Mice.

Superovulation is a crucial step in assisted reproductive technology that involves the administration of gonadotrophins. Repeated superovulations result in severe ovarian damage. The present study investigated the effect of in vivo administration of lycopene on ovarian damage induced by four successive cycles of superovulation. Superovulated mice were simultaneously administered intraperitoneally with saline (R4) or 5 mg/kg lycopene (R4-Lyc). The evaluated parameters were the count of different types of follicles, expression of ovarian antioxidant- and apoptosis-related genes, and serum concentrations of estradiol, progesterone, and inhibin-B. Increased numbers of healthy follicles and a decreased count of atretic follicles were observed in mice of the R4-Lyc group compared to those of the R4 group. Moreover, significantly higher mRNA levels of Sod3, Cat, and Nrf2 and lower mRNA levels of Keap1, Tnf, Nfkb, and Casp3, together with decreased H2O2 concentrations and increased total antioxidant capacity, were detected in the ovaries of lycopene-treated mice. Regarding serum reproductive hormones, elevated concentrations of estradiol, progesterone, and inhibin-B were evident in lycopene-administered mice. The present study reports a significant role of lycopene in alleviating the ovarian damage induced by multiple hormonal superstimulations, which could help to improve the outcomes of in vitro embryo production.

Protease expression in the human and rat cumulus-oocyte complex during the periovulatory period: a role in cumulus-oocyte complex migration†.

The migratory and matrix-invading capacities of the cumulus-oocyte complex have been shown to be important for the ovulatory process. In metastatic cancers, these capacities are due to increased expression of proteases, however, there is limited information on protease expression in the cumulus-oocyte complexes. The present study examined cumulus-oocyte complex expression of plasmins, matrix metalloproteases, and A Disintegrin and Metalloproteinase with Thrombospondin Motifs family members in the rat and human. In the rat, human chorionic gonadotropin (hCG) administration increased cumulus-oocyte complex expression of Mmp2, Mmp9, Mmp13, Mmp14, Mmp16, Adamts1, and the protease inhibitors Timp1, Timp3, and Serpine1 by 8-12h. This ovulatory induction of proteases in vivo could be mimicked by forskolin and ampiregulin treatment of cultured rat cumulus-oocyte complexes with increases observed in Mmp2, Mmp13, Mmp14, Mmp16, Mmp19, Plat, and the protease inhibitors Timp1, Timp3, and Serpine1. Comparison of expression between rat cumulus-oocyte complexes and granulosa cells at the time of ovulation showed decreased Mmp9 and increased Mmp13, Mmp14, Mmp16, Adamts1, Timp1, and Timp3 expression in the cumulus-oocyte complexes. In human, comparison of expression between cumulus and granulosa cells at the time of in vitro fertilization retrieval showed decreased MMP1, MMP2, MMP9, and ADAMTS1, while expression of MMP16, TIMP1, and TIMP3 were increased. Treatment of expanding rat cumulus-oocyte complexes with a broad spectrum matrix metalloproteases inhibitor, GM6001, significantly reduced the migration of cumulus cells in vitro. These data provide evidence that multiple proteases and their inhibitors are expressed in the cumulus-oocyte complex and play an important role in imparting the migratory phenotype of the cumulus-oocyte complex at the time of ovulation. Summary Sentence Multiple proteases and their inhibitors are induced in the cumulus-oocyte complex (COC) during the periovulatory period and potentially play an important role in imparting the migratory phenotype of the COC at the time of ovulation.

Investigational Treatment of Congenital Hypogonadotropic Hypogonadism in Infants.

The aim of the study was to investigate whether the administration of gonadotropins to mimic the physiological development of infants with congenital hypogonadotropic hypogonadism (CHH) after birth can facilitate testicular descent, penile growth, and ultimately preserve fertility. This study included eight infants with CHH who received a gonadotropin-releasing hormone (GnRH) pump or human chorionic gonadotropin (HCG) combined with human menopausal gonadotropin (HMG) therapy at Beijing Children's Hospital from August 2018 to March 2023. The age of the infants ranged from 6 months to 2 years. 2. For literature review, a search was conducted in the PubMed database using the keywords "congenital hypogonadotropic hypogonadism," "infants," and "mini-puberty" up until June 2023. After 1-3 months of treatment, significant increases were observed in PL and TV. The testes descended from the inguinal region to the scrotum. Serum T and INH-B levels increased from being undetectable to 737.1±409.5 ng/dl and from 47.88±23.03 to 168.94±59.34 pg/ml, respectively. In a comparative literature review of 22 infants with CHH, the age at treatment initiation ranged from 0.5 to 7.9 months. Treatment involved various dosages and durations, ranging from 2 to 6 months of subcutaneous injections of LH and FSH. Both therapies successfully improved PL, TV, and testicular descent; reduced the need for surgery; and were safe. This is the first report of the use of a GnRH pump for the treatment of infant CHH.

P-695 Optimizing oocyte donor stimulation: A revelation from 2,666 cases emphasizing the sole efficacy of exogenous FSH

Abstract Study question Does the administration of human menopausal gonadotrophin in controlled ovarian stimulation improve clinical outcomes in the oocyte donation program? Summary answer The addition of hMG (human menopausal gonadotropin) reduces the number of retrieved oocytes without improving embryo development or clinical outcomes in oocyte donation program. What is known already In controlled ovarian stimulation for assisted reproduction treatments, follicle stimulating hormone(FSH) is essential, but the importance of LH supplementation from menopausal origin is controversial. It is a common practice to use hMG to provide the LH effect. The standard preparation contains FSH and LH effects in a 1:1 ratio.The FSH component would recruit ovarian follicles and stimulate their growth, while the LH component would facilitate their maturation. Our aim was to compare the outcomes of intracytoplasmic sperm injection (ICSI) treatments using a gonadotropin-releasing hormone GnRH) antagonist protocol with recombinant FSH(FSHr) alone and supplemented with hMG in the oocyte donation program. Study design, size, duration This is a retrospective cohort study of 2,666 patients enrolled in the oocyte donation program at a single center over four consecutive years. Donor stimulation commenced with daily FSHr injections. The FSHr group (n = 2,078) continued FSHr, while the FSHr+hMG group (n = 588) received hMG. Participants/materials, setting, methods Donors received GnRH agonist via i.m. injection until a mean diameter &amp;gt;18 mm in at least eight follicles. Transvaginal oocyte retrieval was scheduled 36h later, followed by ICSI for all retrieved oocytes. Embryos were cultured in time-lapse systems and evaluated using an artificial intelligence-based model (iDAScore v2). Recipients underwent hormone replacement therapy for endometrial preparation. Our comparative study examined oocytes retrieved, embryo score, implantation, and live birth outcomes in fresh and frozen embryo transfers (ETs). Main results and the role of chance The number of retrieved oocytes was higher in the FSHr group than in the FSHr+hMG group: 24.9±10.6 vs. 18.2±8.8 (p &amp;lt; 0.001). In addition, embryos from the FSHr+hMG group exhibited slower early development, with significantly lower division times to two, three, four and five cells in the FSHr group (p &amp;lt; 0.005). However, late parameters of embryo development showed no differences. Automatic scoring by the deep learning algorithm was identical for blastocysts in the FSHr (4.8±2.8) and FSHr+hMG groups (4.8±2.8); p = 1. Implantation rates showed no significant differences for fresh ET (FSHr: 58.6% vs. FSHr+hMG: 61.9%; n = 2,073; p = 1) or frozen ET (FSHr: 49.3% vs. FSHr+hMG: 46%; n = 2,687; p = 1). Similarly, there were no differences in live birth rates for fresh ET (FSHr: 45.6% vs. FSHr+hMG: 50.3%; n = 1,993; p = 1) or frozen ET (FSHr: 31.8% vs. FSHr+hMG: 33.8%; n = 2,508; p = 1). Limitations, reasons for caution The retrospective and single-center nature of the study would be its main limitations. It is essential to emphasize that these results are only applicable within the oocyte donation program. Wider implications of the findings Based on our findings, the use of exogenous FSHr alone is likely adequate in the GnRH antagonist protocol for optimal ovarian stimulation of donors, leading to the production of high-quality embryos and successful clinical outcomes. Trial registration number Not Applicable

Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes.

Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes. Post-hoc analysis of a prospective observational cohort. Single-center study. 2569 women receiving embryo transfer. None. The main outcomes were oocyte and embryo quality as well as pregnancy outcomes. DBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P<0.001) and E2 x-fold change to baseline level (r = 0.108, P<0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R2 = 0.475, P<0.001) and inversely with free 25(OH)D (r=-0.424, R2=0.179, P<0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes. DBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.

Inhibitory influence of agmatine on catamenial-like seizure susceptibility in progesterone withdrawn female rats

Catamenial epilepsy is a condition marked by an increased occurrence of seizures that coincide with the menstrual cycle in women. Our study explored the role of neurotransmitter/neuromodulator agmatine in progesterone withdrawal induced increased seizure susceptibility that is one of the causes of catamenial epilepsy. Additionally, it investigates potential interactions between agmatine and the central neurosteroid system. The experiments involved the use of female Sprague-Dawley rats. To mime the seizure susceptibility as seen in catamenial epilepsy, rats were treated with PMSG and b-HCG which cause a higher release of progesterone and later injected with Finasteride on the 11th day of post-human chorionic gonadotropin administration to cause a sudden drop of progesterone. On the 12th day, seizure susceptibility was assessed through a low-dose (35 mg/kg) pentylenetetrazol (PTZ) injection. The results revealed that agmatine treatment showed a protective effect against seizures. Furthermore, this study explored the impact of neurosteroids such as allopregnanolone or progesterone (a precursor of allopregnanolone) and neurosteroidogenic drugs like FGIN 1–27 or metyrapone (an 11β-hydroxylase inhibitor) on the anticonvulsant effect of agmatine. The findings indicated that prior administration of these substances significantly enhanced the anticonvulsant effect of agmatine. In contrast, inhibiting neurosteroid production with drugs like trilostane (a 3β-hydroxysteroid dehydrogenase inhibitor) or indomethacin (a 3α-hydroxysteroid dehydrogenase inhibitor) completely nullified agmatine's effect. Seizures were associated with elevated progesterone levels and reduced allopregnanolone levels, which were normalized by agmatine treatment. Notably, agmatine exhibited seizure protection even in ovariectomized rats, affirming the involvement of neurosteroids in its anti-seizure effects in progesterone withdrawal increased seizure susceptibility. In conclusion, these findings emphasize central neurosteroid involvement in agmatine's pharmacological effects against seizure susceptibility in progesterone withdrawal in female rats.

Outcomes of Ovulation Induction Aimed to Pregnancy in Eight Hypopituitarism Patients.

Female sex hormones work in concert. Gonadotropin-releasing hormone and ovulation-inducing agents are required in female patients with infertility owing to hormone dysregulation. Although drug-induced follicular development can be expected in patients with endogenous female hormone deficiency, data are lacking on the protocols and drugs used. We retrospectively examined the success rates of ovulation induction, assisted reproductive technology, and pregnancy outcomes in 66 cycles of eight patients with pituitary insufficiency at our hospital. Ovulation occurred in 75.4% (49/66); 82.6% (38/46) of patients <40 years and 57.9% (11/19) of patients ≥40 years of age. Five of the eight patients became pregnant, and three delivered babies. The fertilization rate was 78% with in vitro fertilization, and the recombinant follicle-stimulating hormone usage was 3,717.1 ± 1,528.9 International Unit in hypopituitarism patients. Hypopituitarism patients can achieve ovulation, pregnancy, and delivery after optimal gonadotropin administration. Further studies are needed to determine the effects of gonadotropins on other pituitary hormones, such as growth hormones.

Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer

The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive. To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility. This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and <10 days), group 2 (≤1500 IU and ≥10 days), group 3 (>1500 IU and <10 days), and group 4 (>1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023. Blastocyst biopsy and PGT-A. The primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer. A total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]). In this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate. ClinicalTrials.gov Identifier: NCT03118141.

Evaluation of Ovarian Histomorphology and Function Following Clomiphene Citrate and Human Chorionic Gonadotropin Administration in Wistar Rats

Polycystic ovarian syndrome (PCOS), affecting 5-10% of women, is a leading cause of infertility affecting 10-15% of couples globally. Human chorionic gonadotropin (hCG) and clomiphene citrate (CC) are often utilized for the treatment of PCOS. Accordingly, this study explored the effects of CC and hCG on ovarian histomorphology and fertility parameters. Twenty adult female rats were divided into four groups as follows: Group A (control) received only feed and water; Group B received 0.7 mg/kg BW of CC twice daily for five days and was mated before sacrifice on day 19 (before litter); Group C received 0.7 mg/kg BW of CC twice daily for five days, followed by mating and allowed to litter before sacrifice; Group D received 0.7 mg/kg body weight (BW) of hCG on day one, followed by 0.7 mg/kg BW of CC twice daily for five days, and were mated before sacrifice on day 7 (before litter). Results showed that Group B rats had higher, more than other groups, Follicle-stimulating hormone (FSH), Estradiol, Testosterone and Prolactin levels when compared to the control. Similarly, rats in Group B had higher levels of Progesterone while Group D had higher levels of Luteinizing hormone (LH) when compared to the control group. Histological findings demonstrated diverse impacts on ovarian structures, ranging from congested blood vessels to haemorrhages and follicular cysts. Consequently, this study underscores the complexities of drug interactions in reproductive health and provides preliminary insights into the possible adverse effects of CC and hCG on the ovary and fertility parameters.

Is there any truth in the myth that IVF treatments involve weight gain?

To examine body weight change in women undergoing in vitro fertilization and embryo transfer (IVF-ET) using antagonist protocol after up to three treatment cycles. A prospective cohort study among IVF patients treated between 2018 and 2019. Each patient underwent weight measurement three times during the treatment cycle: before treatment, at the beginning of the hormonal stimulation, and at the completion of the cycle, on the day of the pregnancy test. Data were also analyzed according to the body mass index (BMI) groups for normal weight, overweight, and obese patients. Finally, weight changes were recorded following altogether 519 treatment cycles, 240, 131, and 148 cycles, for normal weight, overweight, and obese patients, respectively. The change in the patient's weight was clinically non-significant either during the waiting period or during gonadotropin administration, and overall, during the first, second, or third treatment cycles. The recorded mean total weight change of 0.26 ± 1.85, 0.4 ± 1.81, and 0.17 ± 1.7, after the first, second, or third treatment cycles, represent a change of 0.36%, 0.56%, and 0.23% of their initial weights, respectively. This change of less than 1% of the body weight falls short of the clinically significant weight gain of 5%-7%. Analyzing the data for the various BMI groups, the changes observed in body weight were under 1%, hence with no clinical significance. The findings of the study reject the myth that hormone therapy involves clinically significant weight gain, and this can lower the concerns of many patients who are candidates for treatment of assisted reproductive technology.

Risk factors of ectopic pregnancy after in vitro fertilization-embryo transfer in Chinese population: A meta-analysis.

The prevalence of ectopic pregnancy after assisted reproduction is notably high, posing a significant threat to the life safety of pregnant women. Discrepancies in published results and the lack of a comprehensive description of all risk factors have led to ongoing uncertainties concerning ectopic pregnancy after assisted reproduction. This study aimed to understand the risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population and provide a reference for targeted prevention and treatment. A comprehensive search of the China National Knowledge Infrastructure, Wang fang Database, China Science Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Web of Science, and Embase was conducted to identify relevant literature on the risk factors for ectopic pregnancy in Chinese women after assisted reproductive technology in Chinese women. A meta-analysis of the included studies was performed using Stata17. Overall, 34 articles were included in the analysis. The risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population included a thin endometrium on the day of HCG administration and embryo transplantation, a history of ectopic pregnancy, secondary infertility, a history of induced abortion, polycystic ovary syndrome, decreased ovarian reserve, tubal factor infertility, cleavage stage embryo transfer, fresh embryo transfer, artificial cycle protocols, elevated estradiol levels on the day of human chorionic gonadotropin administration, a history of tubal surgery, two or more number of embryo transfers, previous pregnancy history, and a history of pelvic surgery. This study clarified the factors influencing ectopic pregnancy after in vitro fertilization and embryo transfer in the Chinese population, focusing on high-risk groups. Targeted and personalized intervention measures should be adopted to prevent and detect the disease early to reduce its incidence and harm. The protocol for this view was registered in PROSPERO (CRD42023414710).

Equine chorionic gonadotropin treatment and timed artificial insemination for dairy cow production under heat stress.

This study investigated the effects of timed artificial insemination (TAI) and equine chorionic gonadotropin (eCG) administration on lactating dairy cows under heat-stress conditions (average temperature-humidity index: 80). Timed artificial insemination was performed on the cows with (n = 57) or without (control, n = 41) supplementation with 500 IU of eCG at the day of PGF2α treatment using the CIDR-Ovsynch protocol. GnRH was administered, and a progesterone device (CIDR) was inserted on Day -10 of the treatment protocol. The CIDR was removed on Day -3, and the cows were treated with PGF2α. Two days later, a 2nd GnRH injection was administered. Subsequently, AI was performed on Day 0 (16-20 h after the 2nd GnRH injection), and pregnancy was diagnosed on Days 32 and 60. Plasma progesterone (P4) concentrations were measured after AI. Results showed that the eCG group had a higher pregnancy per AI (P/AI) than the control group (43.9 vs. 12.2%, P = 0.002), which was also accompanied by elevated P4 levels. Four cows in the eCG group had multiple calves, representing 7.0 and 16.0% of the group and pregnant cows, respectively. In conclusion, 500 IU of eCG combined with CIDR-Ovsynch in lactating dairy cows under severe heat stress conditions successfully improved fertility. However, the protocol may have a slight risk of multiple births.

Estradiol-to-follicle ratio on human chorionic gonadotropin day is a novel predictor of gestational diabetes mellitus in women receiving fresh embryo transfer.

To assess the predictive value of estradiol (E2) related parameters on the incidence of gestational diabetes mellitus (GDM) in women undergoing fresh embryo transfer. A Post-hoc analysis of a prospective cohort study. We identified an optimal E2/follicle (E2/F) ratio threshold of 246.03 pg/ml on the day of human chorionic gonadotropin (hCG) administration. Women with an E2/F ratio exceeding this threshold had significantly lower rates of GDM (12.75% vs. 20.41%, P < 0.001) and ovarian hyperstimulation syndrome (OHSS) (11.75% vs. 15.48%, P = 0.03). Additional E2 parameters were also evaluated: baseline E2, E2 on hCG day, E2 increase, and E2 fold change. Lower GDM rates were observed in women with baseline E2 above 31.50 pg/ml (13.51% vs. 19.42%, P <0.01), E2 on hCG day above 3794.50 pg/ml (12.26% vs. 19.32%, P < 0.001), and E2 increase above 3771.50 pg/ml (12.24% vs. 19.28%, P < 0.001). There were no significant differences in OHSS rates for these additional E2 parameters. After adjusting for confounders, lower E2/F ratio (OR: 1.626, 95% CI: 1.229-2.150, P <0.01), E2 on hCG day (OR: 1.511, 95% CI: 1.133-2.016, P = 0.01), and E2 increase (OR: 1.522, 95% CI: 1.141-2.031, P <0.01) were identified as risk factors for GDM. This study demonstrates that an E2/F ratio over 246.03 pg/ml is significantly associated with a reduced risk of both GDM and OHSS in women undergoing fresh embryo transfer, highlighting the E2/F ratio as a superior predictive biomarker compared to other E2-related parameters.

Effect of the degree of follicular diameter ≥18mm differentiation on the day of hCG administration to the outcome of controlled ovarian hyperstimulation (COH).

To explore the impact of the level of differentiation in a minimum of two follicles with a diameter of ≥18 mm on the outcome of controlled ovarian hyperstimulation on the day of human chorionic gonadotropin (hCG) administration. Single-center data from January 2018 to December 2021 was retrospectively analyzed for 1,199 patients with fresh embryo transfer for assisted reproduction. The absolute value of the standard deviation of the follicle size of at least 2 follicles ≥18 mm in diameter in both ovaries on the day of hCG was taken as the degree of differentiation of the dominant follicle after ovulation induction, based on the standard deviation response to the degree of dispersion of the data. The degree of follicular differentiation was divided into 3 groups according to the size of the value, and the general clinical conditions, laboratory indexes, and clinical outcomes of the patients in the 3 groups were compared. Among the three groups, the body mass index (BMI) of the ≤1s group was lower than that of the other two groups (P< 0.05), while the follicle-stimulating hormone (FSH) and Anti-Mullerian hormone (AMH) were higher (P< 0.05), and the implantation rate and clinical pregnancy rate were significantly higher than those of the other two groups (P< 0.01). After multifactorial logistic regression to correct for confounding factors, with the ≤1s group as the reference, the implantation rate, hCG-positive rate, clinical pregnancy rate and live birth rate of embryo transfer in the ≥2S group were significantly lower (P< 0.01). The results of curve fitting analysis showed that the live birth rate decreased gradually with the increase of the absolute standard deviation (P=0.0079). Differences in follicle diameters ≥18 mm on the day of hCG injection did not have an impact on embryo quality, but had an impact on pregnancy outcomes. The less the variation in follicle size, the more homogeneous the follicle development and the higher the likelihood of live births.

Intrauterine insemination: prognostic factors.

To evaluate the impact of possible maternal and paternal prognostic factors and ovarian stimulation protocols on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles. Retrospective observational study of 341 IUI cycles performed from January 2016 to November 2020 at the Assisted Reproduction Service of the Clinics Hospital of the Ribeirão Preto Medical School, University of São Paulo. Clinical pregnancy and live birth rates and their potential prognostic factors were evaluated. Wilcoxon's non-parametric test was used to compare quantitative variables, and the chi-square test to compare qualitative variables, adopting a significance level of p<0.05. A logistic regression model was performed to verify which exploratory variables are predictive factors for pregnancy outcome. The ovulation induction protocol using gonadotropins plus letrozole (p=0.0097; OR 4.3286, CI 1.3040 - 14.3684) and post-capacitation progressive sperm ≥ 5million/mL (p=0.0253) showed a statistically significant correlation with the live birth rate. Female and male age, etiology of infertility, obesity, multifollicular growth, endometrial thickness ≥ 7 mm, and time between human chorionic gonadotropin administration and IUI performance were not associated with the primary outcomes. In the group of patients with ideal characteristics (women aged< 40 years, BMI < 30 kg/m2, antral follicle count ≥ 5, partner aged< 45 years, and post-capacitation semen with progressive spermatozoa ≥ 5 million/mL), the rate of clinical pregnancy was 14.8%, while that of live birth, 9.9%. In this study, the ovulation induction protocol with gonadotropins plus letrozole and post-capacitation progressive sperm ≥ 5 million/mL were the only variables that significantly correlated with intrauterine insemination success.

Progestin-primed ovarian stimulation with letrozole using different doses of medroxyprogesterone acetate per day: a retrospective cohort study.

In the progestin-primed ovarian stimulation protocol, the oral administration of medroxyprogesterone acetate has been observed to effectively inhibit the LH surge during ovarian stimulation in patients experiencing infertility. Nevertheless, the use of utilizing medroxyprogesterone acetate during ovarian stimulation can result in more pronounced pituitary suppression, potentially necessitating increased doses of gonadotropins and extended treatment durations. Therefore, it is necessary to determine the optimal dose of medroxyprogesterone acetate, aiming to use relatively lower concentrations of medroxyprogesterone acetate to effectively and safely suppress early LH surges. This retrospective cohort study included 710 patients who underwent cycles of in vitro fertilization or intracytoplasmic sperm injection and were subjected the progestin-primed ovarian stimulation protocol utilizing letrozole between from 1st January 2021 to 31st December 2021. The study population was divided into low, medium, and high concentration groups based on the daily dosage of medroxyprogesterone acetate.The primary focus of this investigation was on the cumulative live birth rate. Secondary outcomes encompassed the occurrence of a premature surge in luteinizing hormone, the quantity of retrieved oocytes, viable embryos, and high-quality embryos, as well as clinical pregnancy rate, abortion rate, ectopic pregnancy rate, and multiple pregnancy rate. In this study, significant differences were observed among three groups in various parameters including body mass index, baseline levels of Anti-Müllerian hormone and luteinizing hormone, antral follicle count, total dose of gonadotropin, and duration of gonadotropin administration (p<0.05). The number of oocytes and viable embryos were significantly higher in medium group and higher than those in the low dose group. Following adjustments for confounding factors related to medroxyprogesterone acetate for various outcome measures, we conducted multiple regression analysis to investigate the independent effects of daily medroxyprogesterone acetate dosage within the combined progestin-primed ovarian stimulation and letrozole protocol. Following multivariable regression analysis, no disparities were found in embryo characteristics (number of oocytes retrieved, number of available embryos, number of high-quality embryos) or pregnancy outcomes (clinical pregnancy rate, cumulative live birth rate) among the three groups. Progestin-primed ovarian stimulation with letrozole using different dose of medroxyprogesterone acetate per day was comparable in terms of the number of oocytes retrieved, the number of high-quality embryos, clinical pregnancy rate and cumulative live birth rate after frozen embryo transfer.

Effects of antioxidant treatment on cell differentiation in rabbit embryos

The antioxidant coenzyme Q10 can influence the expression of genes involved in apoptosis and energy metabolism of oocytes and quercetin can improve oocyte maturation and early embryonic development. In this study, the gene expression of GATA6 and NANOG in rabbit embryos was assessed using the qRT-PCR reaction. The groups were: group A- control group (no treatment added), group B (hormonal treatment of superovulation, which included the administration of PMSG and hCG), group C (administration of quercitin) and group D (administration of Coenzyme Q10). Our results show that the expression of the two genes was different depending on both the stage of embryonic development and the treatment administered. The highest values of gene expression for GATA6 and NANOG were obtained in groups 2, 4, 7, 8 and 9, corresponding to morula and blastocyst stages. In addition to the fact that NANOG and GATA6 are factors that are involved in early embryonic development, we believe that the administration of extrapituitary gonadotropins and antioxidants contributed to the increase in gene expression.