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.

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.

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.

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.

The role of p53, Bcl-2 and Ki-67 in premalignant cervical lesions and cervical cancer.

PURPOSE: The aim of this study was to determine the role of p53, Bcl-2 and Ki-67 expression in the carcinogenesis of cervical carcinoma and aggressiveness of cervical intraepithelial neoplasia (CIN). METHODS: The pathology specimens of 63 patients with a diagnosis of normal squamous epithelium (22 cases), CIN I (14), CIN II (5), CIN III (8) and squamous cell carcinoma (14) were evaluated immunohistochemically for the expression of p53, Bcl-2 and Ki-67 in paraffin sections. RESULTS: The expression of p53 and Ki-67 increased proportionally to the grade of CIN and cervical cancer, but only the increase of p53 expression was statistically significant (p = 0.002). There was no significant correlation between Bcl-2 expression and premalignant and malignant cervical lesions. CONCLUSION: p53 expression may have a role in the carcinogenesis of squamous cell cervical carcinoma whereas Bcl-2 expression has no role. Ki-67 expression can not be used in determining the aggressiveness of CIN lesions.

Preliminary experience with salvage weekly paclitaxel in women with advanced recurrent ovarian carcinoma.

PURPOSE OF INVESTIGATION: To assess the role of palliative chemotherapy with weekly paclitaxel in patients with recurrent ovarian cancer. METHODS: Thirty-two patients with paclitaxel- and platinum-resistant ovarian cancer were treated with weekly paclitaxel at 80 mg/m2 as a 1-hour intravenous infusion weekly for six weeks every eight weeks (1 cycle). This schedule was considered to be given for three cycles. Evaluation of radiographically measurable disease was used in the assessment of response. CA-125 was used to classify responses only in the absence of a measurable lesion. RESULTS: Thirty-two patients were all assessable for response. Of these, nine patients (28.1%) achieved a partial response and one patient achieved a complete response, leading to an overall response rate of 31.2%. Stable disease occurred in six patients (18.8%), and 16 patients (50%) had progressive disease. Nine patients died of progressive disease while on treatment. The median survival for the entire group was 10.5 months (range 2.5-22 months). Grade 3 or 4 leukopenia and neutropenia occurred in eight and six patients, respectively. Four of these patients developed febrile neutropenia without infection. Grade 1 and 2 peripheral neuropathies were observed in 50% of the patients without causing any premature drop out. Severe (grade 3 or 4) peripheral neuropathy was not observed. There were 11 patients with grade 1 or 2 myalgias. CONCLUSION: Weekly paclitaxel regimen is well tolerated with acceptable toxicity. The favorable toxicity profile and the encouraging antitumor activity observed in this study makes this regimen an option for the salvage treatment of patients with recurrent ovarian cancer.