Peritoneal metastasis of advanced epithelial ovarian carcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective international multicentric data analysis.

INTRODUCTION: The purpose of our study was to evaluate outcome data after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis originating from advanced epithelial ovarian carcinoma (PMOC). PATIENTS AND METHODS: A retrospective international multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group. RESULTS: One thousand four hundred and ninety-one patients from 11 specialized units underwent CRS and HIPEC that of those 326 (21.9%) upfront surgeries, 504 (33.8%) interval surgery, and 661(44.3%) recurrent cases. Complete Cytoreduction(CC0/1) was achieved in 1213 patients (81.3%). Treatment -related mortality was 0.8%, major operative complications (Grades 3-5) was 25.1%. Factors associated with major operative complications include prior surgical score (PSS for recurrent cases; RC) PSS>2,p = 0.000), PCI(≤15, >15 cut-off level; p ≤ 0.000), completeness of cytoreduction (CC, p=0.000), high CA125 levels (>25 mg/dl), presence of ascites, high CRP (>5 mg/dl) levels and low albumin levels (below to 2.5 mg/dl) (p ≤ 0.05). The median survival was 58 months in upfront surgery(UFS), 60 months in interval surgery(IS), and 42 months in RC. The overall survival for five years was 45% for UFS, 37% for IS, 28% for RC cases. CCscore (p = 0.000), CA125, CRP and albumin levels (p ≤ 0.05) were predictors for progression free survival. PCI(p ≤ 0.000), major postoperative complications (p = 0.004), incomplete CRS(CC2/3)(p < 0.001), prior chemotherapy (hazard ratio [HR], 3-8; p < 0.001) and PSS>2 for RC were independent predictors of poor overall survival. CONCLUSION: The combined treatment strategy for PMOC may be performed safely with acceptable morbidity and mortality in the specialized units.

What to advise to patients with only one good quality blastocyst, PGT-A or not? Outcomes of 2064 cycles.

PURPOSE: To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) is beneficial for patients who have only one blastocyst available for biopsy or transfer. METHODS: This retrospective study was based on 1126 single blastocyst PGT-A and 938 non-PGT-A cycles, a total of 2064 ART cycles which resulted in a single good quality blastocyst in women between 20 and 45 years old. The PGT-A group had 225 single euploid embryo transfer cycles and the non-PGT-A group had 938 single blastocyst embryo transfer cycles. RESULTS: In the generalized linear mixed model (GLMM), female age and PGT-A variables were found to be significant variables on pregnancy outcomes. In the PGT-A cases, regardless of the effect of other variables, the probabilities of clinical pregnancy and live birth were found to be 3.907 and 3.448 fold higher respectively than in the non-PGT-A cases (p < 0.001). In non PGT-A cases, the probability of a total pregnancy loss was found to be 1.943 fold higher (p = 0.013). CONCLUSION: PGT-A in the presence of a single blastocyst significantly increases clinical pregnancy and live birth rates and decreases total pregnancy losses regardless of age. In addition, aneuploid embryo transfer cancelations prevent ineffective and potentially risky transfers.

Comparison of antagonist mild and long agonist protocols in terms of follicular fluid total antioxidant capacity.

OBJECTIVE: A high dose of prolonged gonadotropins can yield higher numbers of oocytes and embryos. The high dose or prolonged regimens can be associated with ovarian hyperstimulation syndrome (OHSS), multiple gestations, emotional stress, economical burden and treatment dropout. In mild stimulation lower doses and shorter duration times of gonadotropin are used in contrast to the conventional long stimulation protocol in IVF. It has been proposed that supraphysiologic levels of hormones may adversely affect endometrium and oocyte/embryo. Also it has been proposed that oxidative stress (OS) may alter ovarian hormone dynamics and could be further affected by additional exogenous hormonal stimulation. Therefore our aim was to compare follicular fluid total antioxidant capacity (TAC) in antagonist mild and long agonist stimulations. MATERIALS AND METHODS: Forty patients received antagonist mild stimulation, starting on the 5th day of their cycle and forty patients received long agonist treatment. Seventy-five patients undergoing their first IVF cycle were included in the final analysis. Follicular fluid (FF) samples were analyzed for estradiol (E2), antimullerian hormone (AMH) and TAC. RESULTS: FF-Total antioxidant capacity (TAC) levels were higher in the long agonist group as opposed to the antagonist group [1.07 ± 0.04 mmol Trolox equivalent/L vs 1 ± 0.13 mmol Trolox equivalent/L] (Fig. 1). Pregnancy rates were not significantly different between the two treatments. The FF-TAC levels were not different among infertility etiologies (Fig. 3). FF-TAC levels did not have a direct correlation with pregnancy but a positive correlation with the total gonadotropin dose was observed. CONCLUSION: Patients with good ovarian reserves and under the age of 35 effectively responded to mild stimulation treatment. Using lower amounts of gonadotropin, yielded less FF-TAC levels in patients who underwent antagonist mild protocol. In patients under the age of 35, antagonist mild stimulation is a patient friendly and effective procedure when undergoing their first IVF cycle.

Anti-Müllerian hormone and polycystic ovary syndrome: assessment of the clinical pregnancy rates in in vitro fertilization patients.

OBJECTIVE: The purpose of this study is to investigate the role of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) for the prediction of clinical pregnancy rates (CPR) in women with polycystic ovary syndrome (PCOS) undergoing IVF treatment. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: One hundred and fifty consecutive women with PCOS. INTERVENTIONS: All women underwent controlled ovarian stimulation with long agonist protocol followed by IVF procedure. Outcomes of pregnant and non-pregnant groups were compared. MAIN OUTCOME MEASURE: CPR; AMH, FSH and AFC means and percentiles. RESULTS: Fifty-one (34%) clinical pregnancies were observed in 150 women. Mean AMH was 6.7 ± 2.8 and 7.1 ± 4.3 ng/mL in pregnant and non-pregnant women, respectively (p = 0.594). The CPR were 27.8%, 35.0% and 37.8% in <25%, 25%-75% and >75% AMH percentiles, respectively (p = 0.656). There were also no significant difference in mean FSH and AFC between pregnant and non-pregnant women (p = 0.484 and p = 0.165, respectively). CONCLUSION: AMH, FSH and AFC are not predictive for CPR in women with PCOS undergoing IVF treatment. Mean AMH values were not significantly different between pregnant and non-pregnant women. Although CRP increased in parallel with the raise in AMH percentiles, this remained insignificant.

Serum anti-müllerian hormone, follicle stimulating hormone and antral follicle count measurement cannot predict pregnancy rates in IVF/ICSI cycles.

PURPOSE: To investigate whether serum anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), or antral follicle count (AFC) are predictive for clinical pregnancy in in vitro fertilization (IVF) patients. METHODS: Serum AMH, inhibin B, FSH, luteinizing hormone (LH), estradiol (E2), prolactin, and thyroid stimulating hormone (TSH) levels and AFC of 189 women under 40 years of age were investigated. Pregnant and non-pregnant women were compared. RESULTS: Forty-seven (24.8 %) clinical pregnancies were observed in 189 women. There was no significant difference in terms of mean age, duration of infertility, body mass index, AMH, LH, FSH, E2, TSH, Inhibin B, AFC and total oocyte number between women who did and who did not become pregnant. Additionally, there was no significant difference in clinical pregnancy rates between the quartiles of AMH, FSH and AFC. (P values were 0.668, 0.071, and 0.252, respectively.) CONCLUSION: Serum AMH and FSH, and AFC cannot predict clinical pregnancy in IVF patients under 40; the pregnancy rate tends to increase as AMH increases, although this remains non-significant.

The association between homocysteine in the follicular fluid with embryo quality and pregnancy rate in assisted reproductive techniques.

PURPOSE: To investigate the association between follicular fluid homocysteine levels and embryo quality and pregnancy rates in patients undergoing assisted reproduction. METHODS: Fifty infertile women who were admitted to our clinic were enrolled in the study. Ovulation induction was performed by using GnRH agonist and gonadotropins. For each patient, homocysteine level in the follicular fluid was measured by using nephelometric method after the oocyte pick-up. The association between the homocysteine concentration in the follicular fluid and the oocyte-embryo quality, pregnancy rates and hormone levels were investigated. RESULTS: Mean ± SD Hcy was 9.6 ± 2.02 µmol/L and 14.9 ± 2.93 µmol/L in pregnant and non-pregnant women, respectively (p < 0.0001). There were no statistically significant differences between pregnant and non-pregnant women in mean age, duration of infertility, body mass index, the oocyte-embryo quality parameters, and hormone levels. Homocystein did not have any correlation with M2, late M2, and total number of oocytes, number of fertilized oocytes and transferred embryos, and embryo quality grade. Area under curve (AUC) of hcy for prediction of pregnancy failure was 0.922 (p = 0.0001, 95% Confidence interval 0.85-0.99). A threshold of 11.9 µmol/L of hcy had a sensitivity of 82%, specificity of 100%, positive predictive value of 100% and negative predictive value of 91.6% for prediction of pregnancy failure. The subgroup analysis in male factor infertility group (n = 28), showed that mean homocystein was 9.9 ± 2.44 µmol/L and 14.1 ± 2.72 µmol/L in pregnant and non-pregnant women, respectively (p = 0.002). CONCLUSION: Low follicular fluid homocysteine level is associated with a better chance of clinical pregnancy.

Different serum anti-Müllerian hormone concentrations are associated with oocyte quality, embryo development parameters and IVF-ICSI outcomes.

OBJECTIVE: To evaluate the association between different basal serum levels of anti-Müllerian hormone (AMH) and oocyte-embryo quality and IVF outcomes. MATERIALS AND METHODS: Two hundred and nine infertile women who underwent in vitro fertilization treatment with intracytoplasmic sperm injection (ICSI) between January 2009 and February 2011 were included in the study. Mean age, BMI, FSH, E(2), inhibin B, duration of infertility, total gonadotropin dose, antral follicle count, morphology of all oocytes, percentage of MII, early cleavage rate, the number of good quality embryos in transfer and ongoing pregnancy (>12 weeks) rates were evaluated. RESULTS: Six groups were formed according to the percentiles as <10% (≤0.89 ng/ml; n = 21), 10-25% (0.89-1.40 ng/ml; n = 31), 25-50% (1.40-2.89 ng/ml; n = 53), 50-75% (2.89-4.83 ng/ml; n = 28), 75-90% (4.83-8.06 ng/ml; n = 55), >90% (>8.06 ng/ml; n = 21). Central granulation, cytoplasmic granulation, oocyte postmaturity, percentage of embryos, early cleavage and percentage of transferred good quality embryos were significantly different in five groups (ANOVA test). Ongoing pregnancy rate (PR) was the lowest in <10% (9.5%), and the highest in 50-75% group (39.3%). (P = 0.040) CONCLUSION: Different AMH levels may predict the quality of oocytes, presence of postmaturity and nucleoli Z score, early cleavage and ICSI outcomes.

Does granulosa cell apoptosis have a role in the etiology of unexplained infertility?

OBJECTIVE(S): To compare granulosa cell apoptosis in patients with unexplained infertility and tubal factor. Accelerated granulosa cell apoptosis may be the cause of unexplained infertility. STUDY DESIGN: Setting was IVF-ET Unit of Cerrahpasa Medical Faculty, Istanbul University. GnRH analogs and gonadotropins were used for ovulation induction in patients with unexplained infertility (n=15) and tubal factor (n=15) undergoing in vitro fertilization and embryo transfer (IVF-ET) procedures. Following HCG injection and follicular aspiration, apoptosis of granulosa cells was assessed using the in situ DNA nick end labelling method and apoptosis rate was further determined by flow cytometry. Apoptosis rates were compared between two groups. Mann-Whitney's U-test and Student's t-test were used for statistics. RESULTS: Apoptosis rate was significantly higher in the unexplained infertility group (33.20 +/- 35.62% versus 10.10 +/- 17.23%). CONCLUSION(S): Granulosa cell apoptosis seems to have a role in the etiology of unexplained infertility.