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.

Do we overlook predictive factors in Poseidon 1 patients? A retrospective analysis co-evaluating antral follicle counts & diameters.

BACKGROUND: An unexpected impaired ovarian response pertains to an insufficient reaction to controlled ovarian hyperstimulation. This deficient reaction is identified by a reduced count of mature follicles and retrieved oocytes during an IVF cycle, potentially diminishing the likelihood of a successful pregnancy. This research seeks to examine whether the characteristics of antral follicles can serve as predictive indicators for the unexpected impaired ovarian response to controlled ovarian stimulation (COS). METHODS: This retrospective cohort study was conducted at a tertiary university hospital. The electronic database of the ART (assisted reproductive technologies) center was screened between the years 2012-2022. Infertile women under 35 years, with normal ovarian reserve [anti-Müllerian hormone (AMH) > 1.2 ng/ml, antral follicle count (AFC) > 5] who underwent their first controlled ovarian stimulation (COS) cycle were selected. Women with < 9 oocytes retrieved (group 1 of the Poseidon classification) constituted the group A, whereas those with ≥ 9 oocytes severed as control (normo-responders) one (group B). Demographic, anthropometric and hormonal variables together with COS parameters of the two groups were compared. RESULTS: The number of patients with < 9 oocytes (group A) was 404, and those with ≥ 9 oocytes were 602 (group B). The mean age of the group A was significantly higher (30.1 + 2.9 vs. 29.4 + 2.9, p = 0.01). Group A displayed lower AMH and AFC [with interquartile ranges (IQR); AMH 1.6 ng/ml (1-2.6) vs. 3.5 ng/ml (2.2-5.4) p < 0.01, AFC 8 (6-12) vs. 12 (9-17), p < 0.01]. The number of small antral follicles (2-5 mm) of the group A was significantly lower [6 (4-8) vs. 8 (6-12) p < 0.01), while the larger follicles (5-10 mm) remained similar [3 (1-5) vs. 3(1-6) p = 0.3] between the groups. CONCLUSION: The propensity of low ovarian reserve and higher age are the main risk factors for the impaired ovarian response. The proportion of the small antral follicles may be a predictive factor for ovarian response to prevent unexpected poor results.

Reliability of hypo-osmotic swelling test on fresh and frozen-thawed ejaculated or testicular immotile sperm: A sibling oocyte study.

The viability of sperm is a crucial factor for achieving a successful pregnancy in intracytoplasmic sperm injection (ICSI) cycles. The aim of this study was to evaluate the accuracy of the hypo-osmotic swelling test (HOST) in fresh and frozen-thawed sperm samples of different origins (ejaculated/testicular). A retrospective analysis was conducted on the outcomes of 2167 oocytes subjected to ICSI using motile and immotile-HOST-positive sperm from 2011 to 2023. We evaluated embryonic development, as well as clinical, obstetric, and neonatal outcomes in four groups based on different sperm origins (ejaculated/testicular) and processing (fresh/frozen). When comparing the results of ICSI between motile and immotile-HOST-positive sperm within each group, it was observed that there were no significant differences in the outcomes for fresh samples. However, for frozen-thawed samples, fertilization rates and blastocyst development rates were significantly lower when ICSI was performed with immotile-HOST-positive sperm compared to motile sperm. Of note, clinical, obstetric, and neonatal outcomes were statistically similar across all groups. Our findings indicate that HOST is more reliable in fresh samples than in those subjected to the freeze-thaw process. Nonetheless, HOST is considered a safe method for selecting viable sperm in all subgroups.

Comparison of semen parameters in the same patients before and after diagnosis of COVID-19.

Clinical and histopathological evidence suggest that the male reproductive system may be negatively impacted in patients with coronavirus disease (COVID-19). The objective of this study is to investigate the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on semen parameters by comparing semen analyses before and after COVID-19 diagnosis in the same patient. We retrospectively analyzed 342 semen analyses by reviewing medical records. The study included two groups of patients: (i) those who underwent two consecutive semen analyses within 6 months, one before (n = 114) and one after (n = 114) COVID-19 diagnosis, and (ii) a control group (n = 114) that was age-matched and did not receive a diagnosis of COVID-19. The study results indicated a significant decrease in semen volume, total sperm count per ejaculate, progressive motile sperm count, total motile sperm count, and normal sperm morphology after SARS-CoV-2 infection in comparison to their respective values before the infection. Subgroup analyses showed that the duration of COVID-19 diagnosis (short-term vs. long-term) did not impact the changes in semen parameters. However, fever during the COVID-19 process had a negative effect on semen parameters, particularly sperm concentration, unlike in patients without fever. In conclusion, our findings suggest that SARS-CoV-2 infection is associated with a decline in semen quality, which may potentially impact male fertility. Furthermore, it's important to note that the negative effects on semen parameters may persist in the long-term. Our results also indicate that fever during active infection could be a significant risk factor that negatively affects spermatogenesis.

Low Molecular Weight Heparin-Aspirin-Prednisolone Combination Does Not Increase the Live Birth Rate in Recurrent Implantation Failure: A Retrospective Cohort Study.

This study investigates the triple combination of adjuvants (low molecular weight heparin (LMWH)-aspirin-prednisolone) whether it improves the live birth rates of IVF&ICSI patients with previous implantation failure. This retrospective study included 1095 patients with >2 failed either fresh or frozen single embryo transfer cycles between 2014 Jan and 2021 Jan. Patients were divided into two subgroups. Group A consisted of patients with only vaginal progesterone for luteal phase support. Group B consisted of patients with triple (daily subcutaneous LMWH, daily 150 mg aspirin, and daily 16 mg prednisolone) luteal phase supplementation to vaginal progesterone. Demographic parameters, cycle characteristics, embryology, and pregnancy outcomes were compared, and the study's primary outcome was the live birth rate. Demographic parameters were similar between the groups. Positive b-hCG, miscarriage, and live birth rates were similar between groups as Group A vs. Group B, positive b-hCG 30.8% (190/617) vs. 35.4% (169/478), miscarriage rates 4.4% (27/617) vs. 6.7% (32/478), and live birth rates 20.4% (126/617) vs. 23.8% (114/478), respectively. When patients were stratified according to previous failures, live birth rates were still similar. Pregnancy outcomes were significantly improved in only patients with diminished ovarian reserve (Group A vs. Group B, positive b-hCG 24.2% vs. 34.3%, live birth rate 12.1% vs. 21.9%, p < 0.01). Whether the embryo transfer was fresh or frozen-thawed did not affect the results. A combined supplementation of LMWH, aspirin, and prednisolone in the luteal phase does not improve live birth rates of IVF&ICSI patients with previous implantation failure except potentially for patients with diminished ovarian reserve.

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.

Which is more predictive ovarian sensitivity marker if there is discordance between serum anti-Müllerian hormone levels and antral follicle count? A retrospective analysis.

This retrospective study aims to determine the more predictive ovarian reserve marker when there is discordance between anti-Müllerian hormone (AMH) and antral follicle count (AFC) in patients with diminished ovarian reserve (DOR). Patients who underwent ICSI because of DOR were divided into three groups. Group 1: patients with low AMH (<1.1 ng/ml) and AFC (n < 7), group 2: patients with low AMH (<1.1 ng/ml) and normal AFC (n ≥ 7) and group 3: patients with normal AMH (≥1.1 ng/dl) and low AFC (n < 7). Demographic values, follicle output rate (FORT) score and follicle to oocyte index (FOI) score of the groups were compared. Totally, 662 cycles were enrolled in the study. There were 418 cycles in group 1, 167 cycles in group 2 and 77 cycles in group 3. As the primary result, FORT and FOI scores were higher in group 3 than the other two groups. Median FORT Score with quartiles: group 1: 100 (66-150), group 2: 71 (57-100), group 3: 136 (96-200), p<.01 - median FOI score with quartiles: group 1: 83 (50-140), group 2: 71 (40-100), group 3: 116 (66-216), p<.01. In conclusion, serum AMH level has more predictive value for stimulation success if there is discordance with AFC.Impact StatementWhat is already known on this subject? Female age, serum Anti-Müllerian Hormone (AMH) levels, and antral follicle count (AFC) are commonly used to assess ovarian reserve and predict response to ovarian stimulation. AMH and AFC are both positively correlated with ovarian reserve.What do the results of this study add? If there is discordance between AFC and AMH in patients with diminished ovarian reserve (DOR), the ovarian response is better in patients with high AMH and low AFC than the patients with low AMH and high AFC.What are the implications of these findings for clinical practice and/or further research? It is important to assess both AFC and AMH before controlled ovarian hyperstimulation, to predict ovarian response in DOR patients, rather than assessing AFC or AMH alone.

Fertilisation and early embryonic development of immature and rescue in vitro-matured sibling oocytes.

The objective of this study was to assess the effect of rescue in vitro maturation and immediate intracytoplasmic sperm injection (ICSI) application on fertilisation success and early embryonic development of metaphase I (MI) oocytes. This was a retrospective cohort study including 2425 sibling oocytes in 259 ICSI cycles. ICSI was performed on 104 GV (germinal vesicle) oocytes which had reached the metaphase II (MII) stage (Group 1) and 231 MI oocytes which had reached the MII stage (Group 2) following IVM (in vitro maturation). Immediate ICSI was applied following oocyte aspiration on 292 MI stage (Group 3) and 1798 MII stage oocytes (Group 4). Normal fertilisation rates in Groups 1, 2, 3 and 4 were 51.9%, 39%, 30.1% and 59.5%, respectively. The rates of blastocyst development per oocyte and per zygote were calculated as 3.8%, 3.0%, 6.8%, 14.1% and 7.4%, 7.7%, 22.7%, 23.6% for Groups 1, 2, 3 and 4, respectively. The blastocyst development rate was significantly higher in the MI-ICSI group compared with other immature oocytes. Even though performing ICSI on the oocytes at the MI stage on the day of oocyte aspiration resulted in lower fertilisation rates, it was associated with significantly higher rates of blastocyst development.

Are all antral follicles the same? Size of antral follicles as a key predictor for response to controlled ovarian stimulation.

The aim of this study was to evaluate whether antral follicle size has any value with respect to antral follicle count (AFC) in predicting ovarian response to controlled ovarian stimulation. Patients who were considered to be normal responders based on their ovarian reserve markers were consecutively recruited. Total AFC was the number of 2-10 mm follicles in both ovaries. Antral follicles were separated into two subgroups according to the size: 2-5 mm and 6-10 mm follicles. Patients were divided into two main groups according to ovarian response to COS. Group 1 (suboptimal response, 4-9 oocytes retrieved, n = 61) and Group 2 (normal responders, ≥10 oocytes retrieved, n = 65). Demographic parameters were comparable between the groups. The number of 2-5 mm follicles was significantly lower in the suboptimal response group (5 [4:7] and 8 [6:10], respectively, p < .001). The ratio of 2-5 mm follicles to total antral follicles was also significantly lower in Group 1 (44.4% and 75%, respectively, p < .001). The ratio of small antral follicles was positively correlated with ovarian response (r = 0.587, p < .001). In conclusion, the ratio of small (2-5 mm) antral follicles could be a more specific predictive marker than AFC for ovarian response.IMPACT STATEMENTWhat is already known on this subject? Prediction of the ovarian response during ovarian stimulation is commonly based on antral follicle count and anti-mullerian hormone. The ovarian response may be inadequate even in patients with normal antral follicle count and anti-mullerian hormone.What do the results of this study add? A high ratio of small-size (2-5 mm) basal antral follicles is a predictive factor for higher ovarian response to ovarian hyperstimulation.What are the implications of these findings for clinical practice and/or further research? To obtain optimal ovarian response, the antral follicles should be evaluated initially in a more detailed and systematic way by taking their sizes into consideration in addition to their counts. Small antral follicle count rather than whole antral follicle count may be beneficial for optimising the ovarian response. Future studies may determine the cut off values of small antral follicle count for high/poor ovarian response.

Supernumerary embryos, do they show the cycle success in a fresh embryo transfer? A retrospective analysis.

OBJECTIVE: To determine the predictive value of cryopreserved embryos during single fresh blastocyst transfer. METHODS: This retrospective cohort study was conducted at a tertiary university hospital ART center. Patients who underwent a single fresh blastocyst transfer were selected from the electronic database. Patients with diminished ovarian reserve, uterine pathology, advanced age (>40 years) were excluded from the study. Patients were divided into two groups. Group A consisted of patients with only one available embryo for the fresh transfer. Group B consisted of patients with cryopreserved embryos apart from the fresh transferred embryo. Demographic and embryology parameters, pregnancy results were compared. RESULTS: Demographic values, ovarian reserve parameters were comparable between groups. The number of the picked-up oocyte, metaphase-2 oocyte, and two-pronucleus embryo was lower in Group A. Positive pregnancy rates were two-fold higher in Group B (23.4% vs. 50.9% p < .01). Pregnancy results did not change depending on the number of cryopreserved embryos in Group B. CONCLUSION: According to our results, the presence of cryopreserved embryos results in higher pregnancy rates in patients with fresh blastocyst embryo transfer independent from the woman's age and ovarian reserve. Thus, these results may help us to predict the implantation rate before embryo transfer.

Luteal oestradiol for patients with serum oestradiol levels lower than expected per oocyte.

Although the efficiency of progesterone in providing luteal phase support has been established, the role of oestradiol supplementation during the luteal phase remains controversial. We evaluated pregnancy outcomes of patients who had a ratio of serum E2 levels on the hCG day to the number of oocytes retrieved (oestradiol/oocyte ratio - EOR) levels of <100 pg/ml by supporting them with additional oestradiol during the luteal phase. In total, 150 patients with an EOR < 100 pg/ml of oestradiol undergoing antagonist intracytoplasmic sperm injection (ICSI) cycles were randomly assigned into two groups to receive either oral oestradiol (4 mg/d) plus vaginal progesterone (90 mg, 2 × 1/day) (group 1) or vaginal progesterone (90 mg, 2 × 1/d) alone (group 2). Implantation rate following transfer of a single embryo did not differ between the two groups (group 1 = 33.3%; group 2 = 34.9%; p = 0.85). Similarly, both groups gave comparable clinical pregnancy rates per embryo transfer with 31.7% in group 1 compared with 28.6% in group 2 (p = 0.69). In conclusion the study suggests that the addition of 4 mg oral E2 to progesterone does not increase the probability of pregnancy.

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.

Detrimental effects of endometriosis on oocyte morphology in intracytoplasmic sperm injection cycles: a retrospective cohort study.

While an association can be addressed among endometriosis and subfertility, the causal relationship has not been elucidated yet. Impaired oocyte quality in endometriosis patients has been accused for the unsuccessful outcomes of assisted reproductive techniques. There are limited studies in literature evaluated association between endometriosis and oocyte morphology. We conducted this retrospective study to evaluate whether morphological abnormalities of oocytes are more common in women with endometriosis than women with diagnosis of male factor infertility as a source of healthy oocytes. Totally 1568 oocytes, 775 (49.4%) in endometriosis groups and 793 (50.6%) in control group were evaluated for morphological parameters before ICSI cycles. Abnormal oocyte morphology was detected in 352 (22.4%) of 1568 oocytes. Of the abnormal oocytes, 208 (59.1%) were in endometriosis group and 144 (40.9%) in control group (p < .001). The following dysmorphisms were significantly higher in oocytes retrieved from endometriosis group: dark cytoplasm; dark, large or thin zona pellucida; and flat or fragmented polar body (p < .05 for all). When morphological parameters for oocytes of endometriosis patients evaluated, the oocyte defects has increased significantly in endometriosis patients. These findings are thought to be useful to clarify the subfertility in endometriosis patient, which needs to be confirmed with further studies.

Which is worse? Comparison of ART outcome between women with primary or recurrent endometriomas.

STUDY QUESTION: Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma? SUMMARY ANSWER: Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma. WHAT IS ALREADY KNOWN: Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas. STUDY DESIGN, SIZE, DURATION: A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3). LIMITATIONS, REASONS FOR CAUTION: The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment. WIDER IMPLICATIONS OF THE FINDINGS: The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests to declare. TRIAL REGISTRATION NUMBER: None.

Does pituitary suppression affect live birth rate in women with congenital hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A multicenter cohort study.

In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010-2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78-2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients.

Scheduling GnRH antagonist cycles by a short course of oral estradiol administration during early follicular phase: a comparative study with non-scheduled cycles.

This hypothesis generating study investigated whether GnRH antagonist cycles can be scheduled by a short course of oral estradiol administration during the follicular phase without impairing treatment outcome. Thirty-five women who underwent follicular phase estrogen scheduling (ES) of GnRH antagonist cycles were retrospectively matched for age and number of prior failed cycles with 35 women who underwent unscheduled GnRH antagonist cycles. ES group was given 6 mg/day estradiol orally from cycle day 2 until (including) one day before the scheduled start of stimulation. Gonadotropins were started on cycle days 2-3 in the control group. Flexible GnRH antagonist protocol was employed in both groups. ES group received estradiol for a median of 5 days. Total gonadotropin consumption was similar but one more GnRH antagonist injection was required in the ES group. Endometrial thickness on the day of hCG injection was increased in the ES group (12 versus 10 mm, p < 0.01). Number of oocytes, metaphase II oocytes and transferred embryos were similar. Embryo implantation rates were 44.8% versus 34.4% (p = 0.3), and clinical pregnancy rates were 48.6% versus 37.1%, (p = 0.33) in the ES and control groups, respectively. All women in the ES group had oocyte retrieval and embryo transfer within the desired period.

Effective inhibition of cardiomyocyte apoptosis through the combination of trimetazidine and N-acetylcysteine in a rat model of myocardial ischemia and reperfusion injury.

OBJECTIVE: Apoptosis is the early and predominant form of cell death in infarcted myocardia. The aim of the study was to investigate the effects of trimetazidine (TMZ) and N-acetylcysteine (NAC), used alone or in combination, on oxidative stress, infarct size, and ischemia-reperfusion (IR)-induced cardiomyocyte apoptosis in a rat model of myocardial IR. METHODS AND RESULTS: Myocardial IR was established by ligating an area under the left main coronary artery for 30 min followed by 3 h of reperfusion. Saline (1 ml/kg), NAC (50, 150 mg/kg), or TMZ (3, 5 mg/kg) was intravenously injected during the middle of the ischemic period. At the end of the reperfusion, blood samples were collected from the animals to measure serum M30 and M65 levels, which are markers of cell death, the S100b level, which is a marker of inflammation, and the malondialdehyde (MDA) level, which is a marker of oxidative stress. The infarct size was evaluated as the ratio of the infarct area to the risk area. Apoptotic activation was assessed by caspase-3 immunostaining and a TUNEL assay. TMZ and NAC, either alone or in combination, significantly reduced serum MDA levels, infarct area and apoptotic activity compared to those observed in saline group. Interestingly, the infarct area was more smaller in TMZ (3 and 5 mg/kg) injected groups (9.72 ± 1.3% and 9.96 ± 2.3%) than those observed in NAC (50 and 150 mg/kg) (16.1 ± 2.5% and 19.1 ± 2.14%) or TMZ (5 mg/kg)- NAC (150 mg/kg) combination groups (16.9 ± 1.6%). However, the apoptotic activity was reduced more significantly in the combination of TMZ (5 mg/kg)-NAC (50 mg/kg) compared to TMZ-only group. Neither TMZ or NAC treatments nor the combination of the drugs significantly affected serum M30, M65 and S100B levels. CONCLUSION: Intravenous NAC and TMZ administration decreased oxidative stress, infarct area and apoptotic activity in a rat model of IR. Although the combination treatment was more effective in reducing the apoptotic activity than either treatment groups alone, TMZ treatment was more successful in reducing the infarct area than NAC or combination treatments. Present results suggest that, in addition to mechanical attempts to secure myocardial reperfusion, the use of TMZ and NAC may help to reduce IR injury.

Effect of tamoxifen on ovarian reserve: A randomized controlled assessor-blind trial in a mouse model.

OBJECTIVE: To determine whether tamoxifen (TMX) exposure causes a permanent decrease in ovarian reserve. MATERIAL AND METHODS: A randomized controlled assessor-blind trial including 30 adult female inbred BALB/C mice. Fifteen mice in the TMX group were given a single 0.1-mg dose of TMX intraperitoneally. Fifteen mice in the control group were given a single dose of the vehicle at the same volume intraperitoneally. Two cycles later, blood samples were collected for determination of anti-Müllerian hormone (AMH) levels, and the mice were sacrificed. After gonadectomy, ovarian size was measured, and follicles were counted under light microscopy. RESULTS: Median serum AMH levels were 6.53 and 6.14 ng/ml in the control and TMX groups, respectively (p=0.03). Ovarian size was significantly decreased in the TMX group. While the number of primordial (9 vs 8), primary (6 vs 3), and secondary (4.5 vs 5) follicles were similar, there were significantly fewer preantral (11.5 vs 6, p<0.01) and antral (2 vs 1, p: 0.03) follicles, as well as corpora lutea (6 vs 3, p: 0.04), in the TMX group than in the control group. The number of atretic (2.5 vs 5, p: 0.048) follicles was increased in the TMX group. CONCLUSION: Tamoxifen administration leads to arrested growth of gonadotropin-sensitive follicles, while insensitive follicles can remain unaffected. TMX is merely an endocrine disruptor, and it does not cause a decrease in primordial follicle pool.

Effect of repeatedly given CDP-choline on cardiovascular and tissue injury in spinal shock conditions: investigation of the acute phase.

OBJECTIVES: The protective effect of CDP-choline in spinal cord transection and the mediation of its cardiovascular effects were investigated. METHODS: Spinal cords of rats were transected at the T1-T2 levels. CDP-choline (250 mg/kg; intravenous) was administered 2 h and/or 24 h after the injury. KEY FINDINGS: Spinal cord transection caused severe tissue damage, decreased mean arterial pressure, heart rate, plasma adrenaline, and noradrenaline but increased plasma vasopressin levels. Repeated CDP-choline treatment attenuated the degree of tissue injury. Administration of CDP-choline at 2 h after transection transiently increased blood pressure and decreased heart rate, while it produced a small decrease in blood pressure and heart rate when it was given at 24 h. Plasma adrenaline levels were higher in the group where CDP-choline was given repeatedly. Plasma noradrenaline and vasopressin levels did not change additionally after CDP-choline injections in all groups. In order to determine if CDP-choline attenuates the oxidative injury induced by transection, we measured blood superoxide dismutase, glutathione peroxidase activity and malondialdehyde levels. Repeated CDP-choline administration decreased blood superoxide dismutase and glutathione peroxidase activity without any effect on malondialdehyde levels. CONCLUSIONS: Data indicate that repeated intravenous CDP-choline treatment prevents tissue damage in spinal shock conditions in the acute phase. The cardiovascular effects of the drug do not seem to be responsible for this protection but the drug-induced attenuation of the oxidative stress may play a role.