Age and dual trigger were found to be significant predictors of live birth in POSEIDON group 3 and 4 women treated with the GnRH antagonist protocol: a retrospective cohort study.

OBJECTIVE: Despite recent advancements in assisted reproductive technology (ART), the effective management of patients with poor ovarian response (POR) remains a formidable challenge. While various treatment strategies and predictors of live births have been documented to provide guidance to fertility specialists in managing poor responders, research efforts have predominantly encompassed all POSEIDON groups. In this study, our objective was to analyze the factors correlated with live births (LB) within a subset of the POSEIDON groups, with a particular focus on POSEIDON groups 3 and 4. PATIENTS AND METHODS: Charts of 406 patients belonging to POSEIDON groups 3 and 4 who underwent ART treatment at a university-affiliated infertility clinic following a gonadotropin-releasing hormone (GnRH) antagonist cycle between January 2016 and December 2021 were analyzed. Clinically significant factors associated with live births were incorporated into a logistic regression model for multivariate analysis to ascertain independent predictors of LB. Additionally, a receiver operating characteristic (ROC) curve analysis was conducted to establish the optimal cut-off values. RESULTS: Live births were achieved in 48 cycles (8.7%). Female age (OR, 0.930; 95% CI: 0.874-0.991; p < 0.024), baseline serum luteinizing hormone (LH) levels (OR, 0.854; 95% CI: 0.741-0.984; p < 0.029), and dual triggers (OR, 4.004; 95% CI: 1.290-12.426; p < 0.016) were identified as independent factors associated with LB following multivariate logistic regression analysis. The optimal age cut-off was determined to be 33 years, with a sensitivity of 70.8% and specificity of 75%. CONCLUSIONS: Younger age, lower baseline serum LH levels, and dual-trigger administration appear to enhance the likelihood of live birth in POSEIDON groups 3 and 4 following treatments with the GnRH antagonist protocol.

Dual suppression with oral contraceptive pills in GnRH antagonist cycles for patients with polycystic ovary syndrome undergoing intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the effects of a gonadotropin-releasing hormone (GnRH) antagonist protocol, with or without oral contraceptive pill (OCP) pretreatment, in patients with polycystic ovary syndrome (PCOS) undergoing intracytoplasmic sperm injection (ICSI). STUDY DESIGN: In this retrospective cohort study, 410 infertile patients with PCOS were assessed in their first ICSI cycles between January 2006 and June 2013. In Group A (n=208), patients underwent a long luteal GnRH agonist protocol, and in Groups B (n=143) and C (n=59), patients underwent a GnRH antagonist protocol. The patients in Group C also received OCPs containing 30mg of ethinyl oestradiol and 3mg of drospirenone prior to treatment. The main outcome measures were pregnancy and ovarian hyperstimulation syndrome (OHSS) rates. RESULTS: Demographic features, body mass index, duration of infertility, serum baseline hormone levels, cycle outcomes, multiple pregnancy rates, miscarriage rates, OHSS rates, total number of Grade A embryos and total number of transferred embryos were comparable between the groups. Clinical pregnancy rates were 27.4%, 26.6% and 23.7% in Groups A, B and C, respectively (p=0.853). CONCLUSIONS: OCP pretreatment was found to have no beneficial or adverse effects in patients with PCOS undergoing a GnRH antagonist protocol for ICSI, but can be used for cycle scheduling.

Impact of unilateral tubal blockage diagnosed by hysterosalpingography on the success rate of treatment with controlled ovarian stimulation and intrauterine insemination.

The aim of this study was to evaluate the success rates of intrauterine insemination (IUI) in infertile women with unilateral proximal and distal tubal blockage. A total of 161 couples with unilateral tubal blockage and unexplained infertility were included. The primary outcome measure was the cumulative pregnancy rate (CPR). The CPRs after three cycles of IUI were 26.3% (10/38) in patients with unilateral tubal blockage, and 44.7% (55/123) in patients with unexplained infertility (p = 0.043). CPRs were similar in patients with proximal unilateral tubal blockage and unexplained infertility (38.1% vs 44.7%, respectively, p = 0.572). CPR was significantly lower in patients with distal unilateral tubal blockage than in patients with unexplained infertility (11.7% vs 44.7%, respectively, p = 0.01). In conclusion, IVF instead of IUI may be a more appropriate approach for distal unilateral tubal blockage patients.

Serum anti-Mullerian hormone levels correlate with ovarian response in idiopathic hypogonadotropic hypogonadism.

PURPOSE: The role of serum AMH levels in prediction of ovarian response in idiopathic hypogonadotropic hypogonadism (IHH) was evaluated. MATERIAL METHOD(S): Twelve patients with IHH underwent controlled ovarian hyperstimulation (COH) for IVF were enrolled in this prospective study. Serum AMH levels were studied on the 2nd or 3rd day of an induced menstrual cycle by a preceding low-dose oral contraceptive pill treatment. A fixed dose (150-300 IU/day) of hMG was given in all COH cycles. Correlations between serum AMH levels, COH outcomes and embryological data were investigated. RESULTS: Mean serum AMH levels was 3.47 ± 2.15 ng/mL and mean serum peak estradiol was 2196 ± 1705 pg/mL. Mean number of follicles >14 mm, >17 mm on hCG day and MII oocytes were 4.14 ± 3.2, 4 ± 2.5 and 7.28 ± 3.5, respectively. Mean number of grade A embryos and transferred embryos were 3.28 ± 2.4 and 2.5 ± 0.7, respectively. The clinical pregnancy rate per patient was 41.6 % (5/12). Positive correlations were observed between serum AMH levels and MII oocytes (r = 0.84), grade A embryos (r = 0.85), serum peak estradiol levels (r = 0.87), and number of follicles >14 mm (r = 0.83) and >17 mm (r = 0.81) on hCG day, respectively. CONCLUSION: AMH appears as a promising marker of ovarian response in patients with IHH undergoing IVF.

Ovarian cryopreservation.

Cryopreservation of ovarian tissue and future autotransplantation are new promising strategies for fertility preservation in various malignant and non-malignant diseases facing the risk of ovarian failure. Ovarian cortrical tissue pieces or intact whole ovary can be removed by laparoscopy without any significant delay in chemotherapy. Slow freezing and vitrification methods are developed to avoid damage to follicles. Ovarian tissue can be transplanted in an orthotopic or heterotopic location when the patient is cured from the disease. Autotransplantation can be performed if absence of malignant cells in the graft is confirmed. Although the procedures are still experimental, ovarian cryopreservation is the single option in prepubertal girls who have not sexual maturity. Earlier team approach of oncologists and reproductive endocrinologists may provide a more successful and professional way of fertility preservation.

The effect of total abdominal hysterectomy on serum anti-Müllerian hormone levels: a pilot study.

OBJECTIVE: To evaluate the effect of hysterectomy on levels of serum anti-Müllerian hormone (AMH), an indicator of ovarian reserve. METHOD: Twenty-two premenopausal women between 40 and 50 years of age who underwent total abdominal hysterectomy for uterine leiomyoma were enrolled to the patient group and unaffected women in a similar age range constituted the control group. Samples were collected preoperatively and at the 4th month postoperatively from the patients and two times at 4 months apart from the controls. Serum AMH levels were detected with enzyme-linked immunosorbent assay and compared within each group and between groups. RESULTS: Baseline serum AMH values were similar (1.46 ± 2.02 ng/ml for the hysterectomy group and 1.53 ± 1.82 ng/ml for the control group, p = 0.73). Serum AMH levels at month 4 decreased to 0.62 ± 0.9 ng/ml and 1.26 ± 1.78 ng/ml for hysterectomy patients and controls, respectively (p = 0.001 and < 0.001, respectively). Although the percentage median decrease was higher in hysterectomized women (58.9% vs. 28.5%), this was statistically insignificant (p = 0.26). CONCLUSION: Although not statistically significant, our study demonstrated that total abdominal hysterectomy causes 30% more loss of ovarian reserve in addition to the effects of aging. Further research on larger populations is needed to confirm our results and to apply them in clinical practice.

Closure vs non-closure of peritoneum at caesarean section: evaluation of pain.

We evaluated the effect of closure or non-closure of parietal and visceral peritoneum during caesarean section (CS) on post-caesarean pain and analgesic requirement. A total of 94 primigravidas planned for elective CS were prospectively enrolled into closure (n = 46) and non-closure (n = 48) groups. Analgesia was provided by a patient-controlled analgesia pump (PCA) postoperatively. Pain was evaluated using a visual analogue scale (VAS) and verbal rating scale (VRS). Total dose of analgesics administered through PCA and times of analgesia demand and additional analgesics were also assessed. VAS and VRS scores were similar between the groups. The total dose of analgesics administered were similar (p = 0.095) between groups, however the mean number of analgesic demand (p = 0.020) and the additional analgesics (p < 0.001) were higher in the closure group. As a conclusion, the closure or non-closure of the peritoneum does not have any impact on postoperative pain intensity, however the analgesia demand and additional analgesia requirement decreases with non-closure.

Outcomes after early or midfollicular phase LH supplementation in previous inadequate responders.

Second cycle outcomes of 75 patients who had previous inadequate ovarian response with recombinant FSH (rFSH)-only ovarian stimulation during gonadotrophin-releasing hormone analogue (GnRHa) down-regulated cycles were evaluated retrospectively. In these second cycles, both rFSH and human menopausal gonadotrophin (HMG) in GnRHa long down-regulation were given to all patients, HMG initiated either on day 1 (group A, n=37) or day 5-6 of the ovarian stimulation (group B, n=38). Total HMG dose was higher (1198+/-514 IU versus 726+/-469 IU; P<0.001), cumulative rFSH consumption was lower (1823+/-804 IU versus 2863+/-1393 IU; P=0.001) and duration of stimulation was shorter (8.94+/-1.15 days versus 10.37+/-1.80 days; P<0.001) in group A than in group B. No significant differences were found regarding fertilization, implantation or pregnancy rates and embryo quality between the groups. Further analysis by supplementary HMG dose (75 IU versus 150 IU) revealed that total gonadotrophin and HMG consumption was lower in 75 IU-supplemented subgroups. Notably, pregnancy rate was higher in patients where 75 IU HMG was supplemented on day 5-6 of ovarian stimulation, which deserves further evaluation.

Dehydroepiandrosterone supplementation improves ovarian response and cycle outcome in poor responders.

The effect of dehydroepiandrosterone (DHEA) supplementation on cycle outcome was assessed in patients with poor ovarian response. In total, 19 poor responder patients who were scheduled to undergo a second intracytoplasmic sperm injection (ICSI)/embryo transfer cycle were enrolled and first ICSI/embryo transfer cycles were taken as the control group. All subjects were given DHEA supplementation (25 mg t.i.d.) for at least 3 months prior to their second ICSI/embryo transfer cycle. In both cycles a fixed dose of rFSH (300 IU/day) and human menopausal gonadotrophin (HMG) (75 or 150 IU/day) along with a flexible gonadotrophin-releasing hormone (GnRH) antagonist protocol were administered. A favourable decrease was noted in mean day 3 serum oestradiol concentrations after DHEA supplementation (75.14 +/- 28.93 versus 43.07 +/- 11.77; P < 0.01). Increased number of >17 mm follicles (3 +/- 0.7 versus 1.9 +/- 1.3; P < 0.05), MII oocytes (4 +/- 1.8 versus 2.1 +/- 1.8; P < 0.05), top quality day 2 (2.2 +/- 0.8 versus 1.3 +/- 1.1; P < 0.05) and day 3 embryos (1.9 +/- 0.8 versus 0.7 +/- 0.6; P < 0.05) were achieved in DHEA-supplemented cycles. Cycle cancellation rates were reduced (5.3% versus 42.1%; P < 0.01), and the pregnancy rate per patient and clinical pregnancy rate per embryo transfer (47.4% versus 10.5%; P < 0.01 and 44.4% versus 0%; P < 0.01) were improved after DHEA supplementation. DHEA supplementation might enhance ovarian response, reduce cycle cancellation rates and increase embryo quality in poor responders.

The role of telomerase activity in predicting early recurrence of epithelial ovarian cancer after first-line chemotherapy: a prospective clinical study.

PURPOSE OF INVESTIGATION: To investigate the value of telomerase activity (TA) in the detection of early recurrence in primary epithelial ovarian cancer (EOC). METHOD(S): In this study, TA was studied in 30 patients with Stage III EOC and 50 control patients with benign gynecological disease. All enrolled EOC patients had had primary cytoreductive surgery and six cycles of platinum-based first-line chemotherapy previously. Semi-quantative TA measurements were done by TRAP assay in ascites, taken at second-look surgery, of cancer patients and in peritoneal washings, taken during planned surgery, of the control group. RESULT(S): Early recurrence was diagnosed in ten EOC patients (33.3%). Mean TA was statistically higher in EOC patients than in patients with benign disease. However, the mean TA was insignificantly lower in early recurrent EOC patients than in disease-free EOC patients. CONCLUSION(S): The value of TA is limited in the detection of early recurrence in primary EOC.

Assisted reproduction and breast cancer.

Breast cancer is the most frequent cancer in reproductive age women. Although well known causal link between estrogen and breast cancer, the impact of ovulation induction on the risk of breast cancer still remains to be clarified. One of the recently recognized long term adverse effects of adjuvant cytotoxic chemotherapy given for breast cancer is premature ovarian failure and infertility, both of which significantly compromise the quality of life of a cancer survivor. Thanks to significant developments in assisted reproductive technologies these patients may benefit from a wide range of fertility preservation options. The most established technique is embryo cryopreservation; oocyte cryopreservation can be considered in single women; both of which require at least 2 weeks of ovarian stimulation beginning with the onset of the patient's menstrual cycle. Novel ovarian stimulation protocols using tamoxifen and letrozole can be used to increase the margin of safety in estrogen sensitive breast tumors. When there is no time available for ovulation induction, ovarian tissue can be cryopreserved for future transplantation without delay in cancer therapy. The benefit of ovarian protection by gonadotropin-releasing hormone analogues is unproven and unlikely, and thus this treatment should not be recommended as the sole method of fertility preservation.

Depot-medroxyprogesterone acetate in anticoagulated patients with previous hemorrhagic corpus luteum.

OBJECTIVE: To investigate the safety of depot-medroxyprogesterone acetate (DMPA) in women of reproductive age with prosthetic heart valves, as well as the impact of DMPA on the prevention of hemorrhagic corpus luteum in these patients with previous bleeding events. METHODS: In this prospective study we enrolled 13 patients who were receiving chronic anticoagulation for prosthetic heart valves, and who suffered from ovarian bleeding. After the initial bleeding episode(s), DMPA was initiated with the intent of preventing recurrent bleeding events by means of ovulation suppression. Follow-up included close monitoring of anticoagulation intensity, lipid profile, measurement of systolic and diastolic blood pressures and weight, and a general physical and gynecological examination. RESULTS: Of the participating 13 patients, one stopped DMPA after the third injection because she wanted to have a child. Among the remaining 12 women, over a mean follow-up of 39.9 months all patients were well and no hemorrhagic corpus luteum was observed. During the follow-up, anticoagulation intensity, assessed by the international normalized ratio (INR), was in the optimum therapeutic ranges at all times (range 2.5-3.5), except for values of 4.6, 5.8 and 5.9 in three patients at 9, 12 and 24 months, respectively. With regard to lipid profile, we observed a significant decrease in high-density lipoprotein cholesterol levels at 12 months, and significant increases in total cholesterol and triglyceride levels after 30 months compared to baseline serum levels. No significant changes were observed in serum low-density lipoprotein cholesterol levels. Mean body weight was higher at months 12 and 30, compared with baseline values (p > 0.05). CONCLUSION: DMPA, which is an effective contraceptive agent, can be used to prevent bleeding from the corpus luteum by means of ovulation suppression in anticoagulated patients with prosthetic heart valves. However, meticulous surveillance should be provided during the follow-up, including close monitoring of anticoagulation intensity and lipid profile.

Prognostic significance of tumor angiogenesis in epithelial ovarian cancer: in association with transforming growth factor beta and vascular endothelial growth factor.

We aimed to evaluate the prognostic significance of microvessel density (MVD), vascular endothelial growth factor (VEGF), and transforming growth factor beta (TGFbeta), as well as to find out the relationship between MVD, and VEGF and TGFbeta in epithelial ovarian cancer (EOC). Surgical specimens of 47 patients with stage I-IV primary EOC, who underwent extended surgical staging according to FIGO, were investigated. Five- micro m thick tissue sections were immunostained with antibody to factor VIII-related antigen, and MVD was assessed at three separate areas of x200 magnification. Expressions for VEGF and TGFbeta were evaluated by immunohistochemical staining using related monoclonal antibodies. Results were correlated with clinicopathologic factors and survival. We did not find any correlation between MVD and clinicopathologic factors, or patient survival. Similarly, there was no association between the degree of VEGF staining and survival or clinicopathologic factors, except preoperative ascites volume, which was higher in patients showing moderate and intense VEGF staining than those with weak VEGF staining (P = 0.052). The expression of TGFbeta was inversely correlated with preoperative CA-125 levels (P < 0.05). Furthermore, there was no correlation between MVD and the staining intensity of VEGF or TGFbeta. In conclusion, angiogenesis does not appear as a prognostic factor in EOC. We suggest that VEGF is an important mediator of ascites formation, and that TGFbeta, which is supposed to have tissue-specific actions in tumorigenesis, may have growth-inhibitory functions in EOC.

Primary carcinoma of the fallopian tube in a 88 years old woman: review of the literature.

A woman of 88 years old with primary carcinoma of the fallopian tube, the oldest patient reported in the English literature according to the best of our knowledge, was presented. After debulking surgery four courses of chemotherapy including paclitaxel and carboplatin was performed. The patient was free of disease during two years follow-up.