Telomerase activity, telomere length, and the euploidy rate of human embryos.

BACKGROUND: Telomeres maintain chromosome stability, while telomerase counteracts their progressive shortening. Telomere length varies between cell types, with leukocyte telomere length (LTL) decreasing with age. Reduced telomerase activity has been linked to reproductive issues in females, such as low pregnancy rates and premature ovarian failure, with recent studies indicating correlations between telomere length in granulosa cells and IVF outcomes. OBJECTIVES: The study aims to explore the relationship between telomere length, telomerase activity, and euploid blastocyst rate in infertile women undergoing IVF/ICSI PGT-A cycles. METHODS: This prospective study involves 108 patients undergoing controlled ovarian stimulation and PGT-A. Telomere length and telomerase activity were measured in peripheral mononuclear cells and granulosa cells (GC), respectively. RESULTS: The telomere repeat copy number to single gene copy number ratio (T/S) results respectively 0.6 ± 0.8 in leukocytes and 0.7 ± 0.9 in GC. An inverse relationship was found between LTL and the patient's age (p < .01). A higher aneuploid rate was noticed in patients with short LTL, with no differences in ovarian reserve markers (p = .15), number of oocytes retrieved (p = .33), and number of MII (p = 0.42). No significant association was noticed between telomere length in GC and patients' age (p = 0.95), in ovarian reserve markers (p = 0.32), number of oocytes retrieved (p = .58), number of MII (p = .74) and aneuploidy rate (p = .65). CONCLUSION: LTL shows a significant inverse correlation with patient age and higher aneuploidy rates. Telomere length in GCs does not correlate with patient age or reproductive outcomes, indicating differential telomere dynamics between leukocytes and granulosa cells.

PGT-M, a Useful Tool to Manage the Lynch Syndrome Transmission.

Lynch syndrome is one of the most common hereditary cancer sensitivity syndromes and is caused by autosomal-dominant germline mutations in DNA mismatch repair genes. In patients affected by this syndrome, pre-implantation genetic testing for monogenic disorders (PGT-M) could be the elective technique used to prevent the transmission of this hereditary syndrome to offspring. Notably, despite the severity of the condition, some authors have observed a markedly lower demand for PGT-M in these patients compared to those with other hereditary conditions. A 34-year-old woman with a medical history of Lynch syndrome associated with endometrial cancer came to the Villa Mafalda fertility center in Rome in order to conceive a healthy baby. In a pre-implantation genetic testing for aneuploidy (PGT-A) + PGT-M cycle, eight blastocysts were formed. Six out of eight blastocysts were affected by the same mother syndrome. One of the other two was aneuploid and the other one was a mosaic embryo, which resulted in a healthy pregnancy. The aim of this report is to emphasize the importance of a multidisciplinary approach to managing patients with this condition. In vitro fertilization (IVF), specifically PGT-M, is a tool that allow patients to conceive biological children with lower risk of inheriting the disease.

HCG administration after endogenous LH rise negatively influences pregnancy rate in modified natural cycle for frozen-thawed euploid blastocyst transfer: a pilot study.

PURPOSE: The aim of the present study was to evaluate whether in a modified natural cycle (modified-NC) for a frozen-thawed single euploid blastocyst transfer, a critical LH value, above which human chorionic gonadotropin (hCG) administration should be avoided, may be defined. METHODS: One hundred and sixty-seven patients underwent modified natural cycle in order to transfer a single frozen-thawed euploid blastocyst. All embryos were obtained by intracytoplasmic sperm injection and were biopsied at the blastocyst stage and analyzed by means of array comparative genomic hybridization (aCGH). Ovulation was induced using 10.000 IU hCG when the mean follicle diameter was at least of 17 mm, independently from LH values. The primary end points were the hCG-positive test and clinical pregnancy. The interim analysis showed that LH value ≥ 13 mIU/ml on the day of hCG injection may negatively influence the clinical results, suggesting that in this condition, it should be advisable waiting for spontaneous ovulation. RESULTS: Among patients who received hCG for ovulation induction, the hCG-positive test and clinical pregnancy rates in modified-NC were significantly lower in cycles with LH ≥ 13 mIU/ml in respect to those with LH < 13 mIU/ml (45.4 vs 73.3 and 36.4 vs 65.9%, in LH ≥ 13 and LH < 13 groups, respectively). In patients with LH value ≥ 13 mIU/ml, hCG administration led to significantly lower rates of hCG-positive test (45.4 vs 74.5% in hCG administration and spontaneous ovulation groups, respectively) and clinical pregnancy (36.4 vs 64.7% in hCG administration and spontaneous ovulation groups, respectively). The baseline patient characteristics were comparable in all groups. CONCLUSIONS: The findings of this study highlight that LH elevation ≥ 13 mIU/ml prior to hCG administration may negatively affect clinical pregnancy rates in modified-NC for single euploid blastocyst transfer. The LH determination should be routinely performed during follicular monitoring. In the presence of LH level ≥ 13 mIU/ml, hCG administration should be avoided, and the embryo transfer should be planned only after spontaneous follicular rupture.

The endometrial preparation for frozen-thawed euploid blastocyst transfer: a prospective randomized trial comparing clinical results from natural modified cycle and exogenous hormone stimulation with GnRH agonist.

PURPOSE: The aim of the study was to evaluate two methods of endometrial preparation for frozen-thawed single euploid blastocyst transfer: modified natural and artificial cycle with GnRH-agonist pituitary suppression. METHODS: In this prospective, controlled randomized trial, a total of 236 patients undergoing infertility treatment were randomized in 1:1 ratio; 118 received a frozen-thawed single euploid blastocyst transfer in a modified natural cycle and 118 in an artificial cycle with GnRH-agonist pituitary suppression. In the artificial protocol, GnRH-agonist combined with estradiol valerate was administered. In the natural protocol, only final oocyte maturation was induced using human chorionic gonadotropin administration. The primary end-points were the clinical pregnancy and implantation rates; the secondary end-points were the cost-benefit in terms of drug cost and the number of visits and the woman psychological distress caused by the treatment. RESULTS: No significant differences were found in clinical pregnancy, implantation, and miscarriage rates between protocols. The number of clinical and ultrasound controls and the number of laboratory dosages and venous samplings were similar in both study groups. No significant differences were found between the groups in the anxiety and depression values before the start of treatment, on the days of progesterone administration, the blastocyst transfer, and pregnancy test. CONCLUSIONS: The findings of this study evidence that in case of frozen-thawed single euploid blastocyst transfer, both protocols are equally effective in terms of clinical outcomes, cost-benefit, and patient compliance. The choice of endometrial preparation protocol should be based on women menstrual and ovulatory characteristics or otherwise on patient need for cycle planning. TRIAL REGISTRATION: www.clinicaltrials.gov with number NCT02378584.

In women with thyroid autoimmunity, does low-dose prednisolone administration, compared with no adjuvant therapy, improve in vitro fertilization clinical results?

AIM: The objective of the study was to verify if prednisolone treatment may influence the in vitro fertilization (IVF) outcome in euthyroid women affected by thyroid autoimmunity. METHODS: One hundred and ninety-four patients including 60 positive for antithyroid antibodies (ATA) underwent the ovarian stimulation in the standard long protocol for IVF and 30 women received the low-dose prednisolone from the day of oocyte retrieval. RESULTS: The overall, clinical pregnancy and live birth rate in ATA-positive patients receiving prednisolone supplementation was significantly higher when confronted with ATA-positive untreated subjects (60.0% vs 30.0%, P = 0.02; 46.6% vs 16.6%, P = 0.03; and 46.6% vs 20.0%, P = 0.05, respectively). The same parameters in ATA-positive untreated women were significantly lower than in the controls (30.0% vs 50.7%, P = 0.0001; 16.6% vs 38.1%, P = 0.04; and 20.0% vs 40.3%, P = 0.04, respectively). CONCLUSION: There is a strong association between the presence of thyroid autoantibodies and poor IVF outcome. The prednisolone co-treatment may improve the clinical pregnancy rate and reduce the miscarriage rate after IVF in women affected by thyroid autoimmunity.

Accumulation of oocytes from a few modified natural cycles to improve IVF results: a pilot study.

PURPOSE: To evaluate the role of co-transfer of embryos derived from vitrified oocytes accumulated during the previous modified natural cycles and an embryo developed from the last one as an alternative to repetitive single embryo transfer ina fresh modified natural cycle. METHODS: Thirty-six patients underwent ICSI procedure with three frozen natural oocytes supplemented by a fresh one obtained from the fourth modified natural cycle. Thirty-one controls received at least three consecutive single embryo transfer in a fresh modified natural cycle. RESULTS: In the study group the oocyte retrieval, survival and total fertilization rate were 73.0 %, 78.1 %, and 64.5 %, respectively. Fifty-two embryos were transferred in 29 transfers. In the control group the oocyte retrieval and fertilization rate was 77.4 % and 83.7 %, respectively. Fifty single embryo transfers were performed. Of a total 14 pregnancies obtained in the study group 10 were defined as clinical and 4 as abortions. In the control group a total of 8 single clinical pregnancies and 2 miscarriages were encountered. The overall (20.0 % vs 48.2 %) and the clinical (16.0 % vs 34.4 %) pregnancy rate were significantly higher in the study group having cumulative embryo transfer following the oocyte accumulation. CONCLUSIONS: These data demonstrate that the co-transfer of embryos derived from vitrified oocytes accumulated during the previous modified natural cycles and an embryo developed from the last fresh modified natural cycle assure an excellent clinical outcome with the overall and clinical pregnancy rate significantly higher compared to the repetitive single embryo transfer in a fresh modified natural cycle.

Three-day topotecan schedule in heavily pretreated recurrent ovarian cancer patients.

OBJECTIVE: To evaluate the clinical benefit of a 3-day topotecan schedule in heavily pretreated recurrent ovarian cancer patients scheduled for palliative treatment. METHODS: Eligibility criteria were 2 or more prior chemotherapy regimens, Eastern Cooperative Oncology Group performance status of 2 or less; adequate organ function, assessable disease by serum CA-125 measurement before each cycle; and 1 or more cycle of topotecan (1.5 mg/m per day) on 3 consecutive days of a 28-day treatment cycle. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 3. Tumor response, stable disease, and progression were evaluated on the basis of CA-125 levels. RESULTS: A total of 68 patients were considered eligible for the study. Median age was 58 years (range, 40-77 years), and the median number of prior chemotherapy regimens was 2 (range, 2-6). A total of 272 cycles of topotecan were administered, with a median of 4 cycles per patient (range, 1-8). No treatment delays or dose reduction was recorded. Major toxicities were grade 3/4 (18%) neutropenia, neutropenic fever (6%), grade 4 thrombocytopenia (3%), requirements for blood (5%), and platelet transfusions (3%). Thirty-five (54%) of the 64 evaluable patients showed a clinical benefit. Of these, 11 patients (17%) had a partial response, and 24 (37%) had stable disease with a median time to progression of 7.5 months (range, 6-10 months) and 4 months (range, 2-6 months), respectively. CONCLUSION: More than half of heavily pretreated ovarian cancer patients may benefit from 3-day topotecan.

Aortic lymphadenectomy in cervical cancer: anatomy, classification and technique.

Lymphatics are the main pathway of dissemination for gynaecologic malignancies and in particular those with preferential regional spread, so the evaluation of lymph node status has an important role in diagnosis, prognosis and treatment of patients with gynaecologic cancer. Hence, gynecologic oncologist must be familiar with lymphatic anatomy and the ability to perform a systematic retroperitoneal pelvic and aortic lymph node dissection is an important skill in their surgical armamentarium. This review will focus on the performance of systematic aortic lymphadenectomy in cervical cancer.

Persistent posttrachelectomy cervical stenosis treated with Petit-Le Four pessary in early cervical cancer patients: a report of two cases.

OBJECTIVE: To report on posttrachelectomy refractory cervical stenosis in two women with early cervical cancer that was resolved by using a Petit-Le Four tube, an older type of cervical pessary. DESIGN: Case report. SETTING: Tertiary care, university hospital. PATIENT(S): Two young women with FIGO stage IB1 cervical cancer and posttrachelectomy cervical stenosis. INTERVENTION(S): Cervical dilatations and Petit-Le Four cervical pessary insertion. MAIN OUTCOME MEASURE(S): Treatment of hematometra, pelvic pain, and infertility. RESULT(S): The Petit-Le Four cervical pessary is a good therapeutic option for the treatment of cervical stenosis after trachelectomy performed for early cervical cancer. CONCLUSION(S): Persistent hematometra from cervical stenosis could compromise both fertility and quality of life, and often requires dilatation of the cervical ostium, which must be performed several times in the same patient to obtain optimal results. Cervical dilators left in place could help physicians in the treatment of recurrent cervical stenosis after trachelectomy.