Dehydroepiandrosterone modulates the PTEN/PI3K/AKT signaling pathway to alleviate 4-vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats.

Dehydroepiandrosterone (DHEA) is frequently integrated as an adjuvant in over a quarter of controlled ovarian hyperstimulation (COH) protocols, despite the ongoing debate regarding its impact. This study aimed to evaluate the efficacy and mechanism of action of DHEA on ovarian follicular development and ovarian response in rats with varying ovarian reserves. The study involved 75 rats categorized into 15 distinct groups. The ovarian tissues of rats in both the normal ovarian reserve group and the premature ovarian insufficiency (POI) group, induced by 4-vinylcyclohexene diepoxide (VCD) injection, were subjected to histomorphological and biochemical analyses following the administration of DHEA, either alone or in combination with COH. Follicle counting was performed on histological sections obtained from various tissues. Serum concentrations of anti-Müllerian hormone (AMH) and the quantification of specific proteins in ovarian tissue, including phosphatase and tensin homolog of chromosome 10 (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT), cyclooxygenase 2 (COX-2), caspase-3, as well as assessments of total antioxidant status and total oxidant status, were conducted employing the ELISA method. The impact of DHEA exhibited variability based on ovarian reserve. In the POI model, DHEA augmented follicular development and ovarian response to the COH protocol by upregulating the PTEN/PI3K/AKT signaling pathway, mitigating apoptosis, inflammation, and oxidative stress, contrary to its effects in the normal ovarian reserve group. In conclusion, it has been determined that DHEA may exert beneficial effects on ovarian stimulation response by enhancing the initiation of primordial follicles and supporting antral follicle populations.

The Kisspeptin and Kisspeptin receptor in follicular microenvironment: is that really necessary for oocyte maturation and fertilisation?

The aim of this study was to determine whether Kisspeptin and Kisspeptin receptor in the follicular microenvironment is necessary for human oocyte maturation and fertilisation. The cumulus cell (CC) and follicle fluids (FF) obtained from the first aspirated follicles (n = 52) from 32 patients were divided into three groups considering nuclear maturation and fertilisation results of oocytes: (1) Metaphase I or germinal vesicle stage oocytes (incomplete nuclear maturation, n = 10), (2) unfertilised metaphase II oocytes (incomplete cytoplasmic maturation, n = 16), and (3) fertilised metaphase II oocytes (completed nuclear-cytoplasmic maturation, n = 26). The gene expression levels were assessed by RT-PCR. The levels of Kisspeptin (KISS1) and Kisspeptin receptor (KISS1R) were measured by ELISA. There were no significant efficacy KISS1 and KISS1R gene expressions in cumulus cells in terms of oocyte nuclear maturation stage (Group 1, vs Group 2 + Group 3) (respectively p = .49; p = .45). In terms of the cytoplasmic maturation stage (Group 2, vs Group 3); KISS1 and KISS1R expressions in CCs were comparable (respectively p = .07; p = .08). In FFs, KISS1 and KISS1R concentrations were similar between all groups (respectively p = .86; p = .26). In conclusion, the relative KISS1 and KISS1R expressions in CC and also KISS1 and KISS1R level of FF were independent of oocytes nuclear and/or cytoplasmic maturation. Impact statementWhat is already known on this subject? It has been demonstrated that Kisspeptin is an essential regulator of reproductive function and plays a key role in the modulation of GnRH secretion and gonadotropin release. Still, no information is available about the link between gene expression or concentration in the follicular microenvironment and oocyte development.What do the results of this study add? The study has shown that the relative Kisspeptin (KISS1) and Kisspeptin receptor (KISS1R) and expressions in cumulus cell (CC) and also KISS1 and KISS1R levels of follicle fluids (FF) were independent of oocytes nuclear and/or cytoplasmic maturation.What are the implications of these findings for clinical practice and/or further research? Based on the findings, it is difficult to establish a concept that kisspeptin can directly induce oocyte maturation. Nevertheless, to confirm these findings, further studies with a larger sample size are needed.

What is the effect of embryo morphology on serum ß-hCG levels?

OBJECTIVE: To determine the effect of embryonic factors on serum beta human chorionic gonadotropin (ß-hCG) levels in pregnancy and live birth resulting after a single fresh cleavage embryo and blastocyst transfer. STUDY DESIGN: This was a retrospective cohort study conducted at a tertiary care hospital. All fresh single embryo transfers (sETs) between September 2011 and December 2016 were included. The correlation analysis was performed to determine the association of embryo morphological parameters on mean serum ß-hCG levels on day 12 after the transfer of a fresh single cleavage embryo and a fresh single blastocyst embryo. RESULTS: Out of a total of 455 fresh sETs, 60 positive ß-hCG results after the transfer of a single fresh cleavage-stage embryo and 82 after the transfer of a single fresh blastocyst. The mean ß-hCG level resulting from a single fresh blastocyst ET was 371.7 ± 52.7 IU/L, which was similar to the mean ß-hCG level resulting from a cleavage ET (314.5 ± 36.9 IU/L) (p = .70). Interestingly, serum ß-hCG levels resulting from a single fresh blastocyst ET showed a correlation with day 5 blastocoele expansion, trophectoderm cell number and blastocyst quality score in ongoing pregnancy (r = .33, p = .02; r = .29, p = .04; and r = .31, p = .03, respectively). Moreover, day 5 blastocoele expansion and blastocyst quality score showed a correlation with the serum ß-hCG levels resulting from a single fresh blastocyst ET in live birth (r = .36, p = .02; r = .31, p = .04, respectively). CONCLUSION: Our study suggests that serum ß-hCG levels resulting from a single fresh blastocyst ET showed a correlation with day 5 blastocoele expansion and blastocyst quality score in both ongoing pregnancy and live birth.