Comparison of the impact of laparoscopic endometriotic cystectomy and vaporization on postoperative serum anti-Mullerian hormone levels.

INTRODUCTION: The aim of this study was to investigate the effect of laparoscopic endometriotic cystectomy and vaporization on ovarian reserve. METHODS: We prospectively analyzed the serum level of anti-Mullerian hormone (AMH) in 62 patients at four different time points- preoperatively and at 1 month, 6 months, and 1 year postoperatively. Among the 62 cases, a bilateral cystectomy was performed in 10, bilateral vaporization in 16, a unilateral cystectomy in 24, and unilateral vaporization in 12. RESULTS: The rate of AMH decline after unilateral cystectomy or bilateral cystectomy was higher than that after unilateral vaporization or bilateral vaporization. Age and bilaterality were associated with an AMH decline at 1 month, and age alone was associated with an AMH decline at 1 year. Moreover, being older than 38 years of age and having a revised American Society for Reproductive Medicine score >80 were independent risk factors for the non-recovery of AMH. CONCLUSION: The rate of AMH decline after laparoscopic endometriotic vaporization is significantly lower than that after cystectomy. Both methods, however, have the potential to lower ovarian reserve, especially in cases of severe endometriosis or in patients older than 38 years of age.

Analyzing the risk factors for a diminished oocyte retrieval rate under controlled ovarian stimulation.

Aim: To investigate which risk factors contribute to a lower oocyte retrieval ratio in women who are receiving controlled ovarian hyperstimulation. Methods: The authors retrospectively analyzed 329 in vitro fertilization (IVF) cycles under controlled ovarian hyperstimulation by using a gonadotropin-releasing hormone antagonist or agonist at Osaka Medical College, Japan. The patients were classified into five groups: advanced age, male infertility, severe endometriosis, tubal infertility, and unexplained infertility. The primary outcomes were the patients' age, oocyte retrieval ratio, serum basal follicle-stimulating hormone, total dose of gonadotropin, and the clinical outcome. A secondary outcome was the stepwise multivariate logistic regression analysis to assess the factors associated with the failure of oocyte retrieval. Results: The oocyte retrieval ratio declined significantly with the patient's age. The ratio of endometriosis in unsuccessful cases was significantly higher than that in successful cycles. Advanced age and endometriosis were the factors that were significantly associated with a lowered oocyte retrieval rate. Conclusion: Advanced age and endometriosis are high-risk factors that contribute to oocyte retrieval failure in infertile patients who are receiving IVF treatment.

Lower FOXO3 mRNA expression in granulosa cells is involved in unexplained infertility.

AIM: The aim of this study was to investigate whether FOXO1 and FOXO3 mRNA expression in granulosa cells is the cause of unexplained infertility. METHODS: Thirty-one patients aged <40 years (13 with unexplained infertility and 18 with male partner infertility as a control group) whose serum anti-Müllerian hormone level was >0.5 ng/µL were enrolled in the study. All patients underwent oocyte retrieval under a short protocol from June 2012 to October 2013. Real-time PCR was carried out using mRNA extracted from granulosa cells retrieved from mature follicles. We compared FOXO1 and FOXO3 mRNA expression ratios in granulosa cells between the unexplained infertility group and the male infertility group. The relation between FOXO1 and FOXO3 mRNA expression ratios in granulosa cells and assisted reproduction technology clinical outcome was also examined. RESULTS: FOXO3 mRNA expression ratio was significantly lower in the unexplained infertility group than in the male infertility group. Moreover, FOXO3 mRNA expression ratio showed a positive correlation with both the number of retrieved oocytes and serum anti-Müllerian hormone level. A positive correlation was also identified between FOXO1 mRNA expression and total dose of hMG. As well, the number of retrieved oocytes in the unexplained infertility group was statistically lower than that in the male infertility group. CONCLUSION: A lower FOXO3 mRNA expression in granulosa cells leads to poor oocyte development in patients with unexplained infertility undergoing controlled ovarian stimulation for in vitro fertilization-embryo transfer.

The effect of moderate to severe endometriosis on expression of growth differentiation factor-9 mRNA in human granulosa cells under controlled ovarian hyperstimulation.

Purpose: To investigate the effect of moderate to severe endometriosis on mRNA expression of growth differentiation factor-9 (GDF-9) in the granulosa cells of mature follicles. Methods: Follicular fluid (FF) was obtained from 13 patients with moderate to severe endometriosis and 11 without endometriosis, as a control group, and GDF-9 protein levels in both were assayed by western blotting. mRNA expression by GDF-9 and LH receptor (LHR) in granulosa cells obtained from all patients in the study were investigated by StepOne Real-Time PCR. Results: Although GDF-9 in FF from patients with endometriosis was no different from that of controls, GDF-9 mRNA expression in granulosa cells of patients with endometriosis was statistically significantly lower than for the control group. The number of oocytes and high-quality embryos was positively correlated with GDF-9 mRNA expression in controls but not in patients with endometriosis Moreover, a negative correlation was identified between GDF-9 mRNA expression and serum estrogen and progesterone levels in the control group, whereas no correlation was observed for the endometriosis group. Conclusions: Moderate to severe endometriosis can significantly reduce GDF-9 mRNA expression in the granulosa cells of patients with the disease compared with those without, thus causing poor oocyte maturation and lower embryo quality.

Compared with cystectomy, is ovarian vaporization of endometriotic cysts truly more effective in maintaining ovarian reserve?

STUDY OBJECTIVE: To evaluate how endometriotic cystectomy and vaporization affect ovarian reserve after conservative surgery. DESIGN: Prospective study (Canadian Task Force classification II-1). SETTING: Hokusetsu General Hospital. PATIENTS: Ninety-nine women who underwent conservative surgery to treat endometriotic cysts from June 2011 to July 2013. INTERVENTIONS: Vaporization with bipolar current was performed in nulligravid women, and cystectomy in those who had a child. In women with endometriotic cysts, bilateral cystectomy was performed in 28, bilateral vaporization in 15, unilateral cystectomy in 40, and unilateral vaporization in 16. In all patients, preoperative and postoperative serum anti-müllerian hormone (AMH) and follicle-stimulating hormone (FSH) concentrations at the early proliferative phase were assayed, and the change in concentrations was evaluated for each operation. MEASUREMENT AND MAIN RESULTS: In the bilateral cystectomy group, the mean (SD) postoperative FSH concentration (19.3 [21.8] IU/mL) was statistically higher than the preoperative concentration (9.0 [6.2] IU/mL) (p < .01). AMH significantly declined after all operations to treat endometriotic cysts, and the rate of decline in the AMH concentration was >50% compared with preoperative concentrations. CONCLUSION: Whether endometriotic cysts are unilateral or bilateral, both cystectomy and vaporization using bipolar current can lower ovarian reserve. Therefore, it is necessary to develop more effective surgical procedures to prevent ovarian damage.

Analyzing the possible involvement of anti-Müllerian hormone and anti-Müllerian hormone receptor II single nucleotide polymorphism in infertility.

PURPOSE: We performed TaqMan genotyping assays of anti-Mullerian hormone (AMH) and anti-Mullerian hormone receptor type II (AMHRII) single nucleotide polymorphisms (SNPs) in order to investigate how their frequency and distribution affect infertility treatment outcome. METHODS: Eighty Japanese women (advanced age: n = 51, endometriosis: n = 18, male infertility as a control: n = 11) who undertook ART were included in the study, and all couples underwent a full infertility investigation protocol. In order to investigate the natural distribution of SNPs, a naturally pregnant group of 28 subjects was recruited from among women who conceived naturally and subsequently delivered in our department. Genomic DNA was extracted from peripheral blood and genotyping was conducted by TaqMan genotyping assay. The relationship of AMH and AMHRII SNPs and treatment outcome in infertile women. Comparison of allele and genotype frequencies of infertile patients with naturally pregnant women. RESULTS: AMHRII -482 A>G homozygote mutation was complicated with ISV 5-6 C>T homozygote mutation and showed a significantly lower oocyte retrieval rate compared with a wild type. Two of 3 cases of AMHRII -482 A>G homozygote mutation were poor responders, and the distribution and frequency of each allele of naturally pregnant women showed no statistical difference compared with infertile women. CONCLUSIONS: This study revealed the possible involvement of AMHRII -482 A>G polymorphism on the malfunction of follicular development in Japanese women.

Difference in mitochondrial gene expression in granulosa cells between recombinant FSH and hMG cycles under in vitro fertilization and transfer.

PURPOSE: Examination of the mitochondrial mRNA expression in granulosa cells from an unspecified population of infertile patients to evaluate whether recombinant follicle stimulating hormone (recFSH) is more effective in producing higher quality embryo rates compared with human menopausal gonadotropin (hMG). METHOD: Thirty-nine patients who underwent the in vitro fertilization and embryo transfer program were retrospectively examined. Patients were administered recFSH (n = 18) or hMG (n = 20) in a long protocol where GnRH agonist was used. Granulosa cells were obtained during oocyte retrieval and examined for mitochondria mRNA expression ratio against GAPDH. Expressions of mitochondria mRNA were evaluated by real-time PCR analysis. RESULTS: The high-quality embryo rate in the hMG cycle was higher than in the recFSH cycle, and the total dose of hMG showed a positive correlation with the expression level of mitochondrial genes in granulosa cells. Moreover, mitochondria mRNA expression was higher in the hMG cycle than in the recFSH cycle. CONCLUSIONS: Compared with recFSH, hMG induces a higher mitochondrial gene expression ratio in granulosa cells at the time of oocyte retrieval and, therefore, may lead to higher quality embryo rates.