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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.

Research Question: Which factors influence the success rate of egg donation programmes with imported vitrified oocytes?, Design: Observational longitudinal cohort study of 431 oocyte donation cycles conducted between January 2015 and February 2019. A total of 398 couples underwent an IVF cycle with imported donated vitrified eggs. All consecutive oocyte donation cycles conducted at the Centre for Reproductive Medicine of the European Hospital in Rome, Italy, were included., Results: A univariable analysis was conducted. Among the demographic characteristics studied, body mass index (BMI) was significantly able to influence outcome. In 49% of unsuccessful cycles, men were overweight, compared with 39.4% in cycles with a positive beta-HCG test (P = 0.03). The relationship between female or donor BMI and treatment outcome, however, was not statistically significant. The day on which the embryo is transferred affects the outcome of the cycle: transferring on day 2 versus day 5 reduces the probability of clinical pregnancy. The relationship between male BMI classes and semen parameters was studied: obese men have a significantly lower sperm concentration than normal-weight men (P = 0.006 after Bonferroni correction). No statistically significant differences were found in semen volume (P = 0.722), sperm morphology (P = 0.100) and motility (P = 0.179) in obese men compared with normal weight men., Conclusion: In addition to the number of oocytes available after warming, male BMI, semen characteristics and blastocyst transfer are critical parameters able to influence the reproductive outcomes of egg donation programmes with imported vitrified oocytes., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: The need for protective measures during the COVID-19 pandemic forced assisted reproduction centers to adopt new protocols in order to reduce the risk of infection for patients and staff. A COVID-19 Compliant IVF ( in vitro fertilization) program based on the use of follitropin delta to induce ovarian stimulation and fixed protocol with GnRH (Gonadotropin-Releasing Hormone) antagonists was applied to demonstrate the efficacy of this program in reducing the necessity of patients to be present within the clinic while maintaining the expected success rate., Methods: The program was applied to 100 patients (women aged between 20 and 40 years, at their first IVF cycle): pretreatment assessment was carried out via video conference and clinical documentations were sent by email. Ovarian stimulation was based on doses of Follitropin delta selected on the basis of body weight and serum AMH (Anti-Müllerian Hormone). The study population was then compared with historical controls to assess the percentage of patients receiving fresh embryo transfer. Finally, a questionnaire was proposed to assess patient satisfaction., Results: The ovarian stimulation protocol with a fixed dose of follitropin delta led to an optimal ovarian response (8-14 oocytes) in 54% of the women included in the study. The rate of hyper response was 15% and was significantly lower that what reported in the control group (26.8%, p  < .05). The good control of ovarian response to stimulation is the reason for the large percentage of cycles associated with fresh embryo transfer (84%, n 84/100). The rate of fresh embryo transfer was significantly higher that what reported for the control population (68.5%, p  < .05). In 40 out of 84 patients, blastocysts were available for the fresh embryo transfer procedure. Eighty-five percent (89/100) of survey responders reported being extremely satisfied with the simplified approach to the IVF cycle because of reduced number of visits, easy management of working hours and reduction in travel costs., Conclusions: The use of follitropin delta and fixed protocol with GnRH antagonist in COVID-19 - Compliant IVF program is associated to a low percentage of patients developing excessive ovarian response compared to conventional strategy and a very good level of patient satisfaction. Beyond the pandemic, the new approach to ovarian stimulation, modern technologies and telemedicine could play a key role in bridging the gap between different geographic areas and could offer advantages such as increased accessibility, cost saving and patient satisfaction.

Background: Preimplantation genetic testing (PGT) is widely used today in in-vitro fertilization (IVF) centers over the world for selecting euploid embryos for transfer and to improve clinical outcomes in terms of embryo implantation, clinical pregnancy, and live birth rates., Methods: We report the current knowledge concerning these procedures and the results from different clinical indications in which PGT is commonly applied., Results: This paper illustrates different molecular techniques used for this purpose and the clinical significance of the different oocyte and embryo stage (polar bodies, cleavage embryo, and blastocyst) at which it is possible to perform sampling biopsies for PGT. Finally, genetic origin and clinical significance of embryo mosaicism are illustrated., Conclusions: The preimplantation genetic testing is a valid technique to evaluated embryo euploidy and mosaicism before transfer.

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.

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.

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., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Purpose of Review: The current review aims to provide an overview of the already available and emerging treatment modalities for caesarean scar pregnancy (CSP)., Recent Findings: CSP is a type of ectopic gestation associated with a high risk of serious complications. The cause of this condition and the best management are still unclear. However, some medical and surgical treatment modalities have been suggested. The main objectives in the clinical management of CSP should be the prevention of massive blood loss and the conservation of the uterus to maintain further fertility, women's health and quality of life. Current data suggest that expectant management should not be recommended, whereas there are accumulating data suggesting that early diagnosis offers single or combined medical and surgical treatment options avoiding uterine rupture and haemorrhage, thus preserving the uterus and fertility., Summary: No universal treatment guidelines for management of CSP have been published up to now. The lack of data on the best evidence should encourage any individual case report and further multicentre studies for recommendation establishment.

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.

Objective: To retrospectively evaluate whether sperm vacuoles influence clinical results, with a particular focus on live-birth rates, in 101 intracytoplasmic morphologically selected sperm injection (IMSI) cycles., Design: Retrospective, observational study., Setting: Medical center., Patient(s): A total of 101 couples with at least two failed intracytoplasmic sperm injection (ICSI) attempts and impaired sperm morphology., Intervention(s): Patients divided into two groups according to sperm morphology and vacuolization pattern: group A comprising patients with good quality spermatozoa (type I and/or type II spermatozoa) (n = 63 patients); group B comprising patients with low quality spermatozoa (type III and/or IV spermatozoa) (n = 38 patients)., Main Outcome Measure(s): Fertilization rate, embryo quality, pregnancy, implantation, and live-birth rates., Result(s): No statistically significant differences were observed between group A and B with regard to "early" assisted reproduction outcomes (fertilization rate and embryo quality). However, the "late" outcomes (pregnancy, implantation, and live-birth rates) were statistically significantly higher in group A., Conclusion(s): These results confirm a correlation between sperm vacuoles and a negative IMSI outcome, suggesting that sperm vacuoles are related to the late paternal effect., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficiency of slush nitrogen vitrification of human oocytes with or without cumulus cells in terms of survival rate and maintenance of meiotic spindle., Design: Randomized, comparative study., Setting: Medical center., Patient(s): A total of 274 oocytes obtained from 46 couples undergoing infertility treatment., Intervention(s): Metaphase II oocytes were divided into groups A and B, vitrified with and without cumulus cells, respectively., Main Outcomes Measure(s): Survival rates and maintenance of meiotic spindle observed immediately after warming and 3 hours after incubation., Result(s): No statistically significant difference was detected between the two groups in terms of survival rate, but a significantly higher percentage of detectable spindle was observed in group B (completely denuded oocytes), either immediately after warming or 3 hours after incubation., Conclusion(s): Complete denudation of oocytes before slush nitrogen vitrification does not influence survival rates but positively affects oocyte meiotic spindle competence. These data support the hypothesis that cumulus cells during vitrification represent an obstacle to cryoprotectant penetration more than having a protective role for the oocyte., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The current review aims to provide an overview of the already available and emerging treatment modalities for caesarean scar pregnancy (CSP)., Recent Findings: CSP is a type of ectopic gestation associated with a high risk of serious complications. The cause of this condition and the best management are still unclear. However, some medical and surgical treatment modalities have been suggested. The main objectives in the clinical management of CSP should be the prevention of massive blood loss and the conservation of the uterus to maintain further fertility, women's health and quality of life. Current data suggest that expectant management should not be recommended, whereas there are accumulating data suggesting that early diagnosis offers single or combined medical and surgical treatment options avoiding uterine rupture and haemorrhage, thus preserving the uterus and fertility., Summary: No universal treatment guidelines for the management of CSP have been published up to now. The lack of data on the best evidence should encourage any individual case report and further multicentre studies for recommendations establishment.

Objective: To report a case of a triplet heterotopic caesarean scar pregnancy (CSP) with two gestational sacs implanted in the caesarean scar after in vitro fertilization-embryo transfer., Design: Case report., Settings: Private reproductive medicine center and obstetric department of a university hospital., Patient(s): A 31-year-old woman with previous caesarean section affected by secondary infertility related to male azoospermia., Intervention(s): In vitro fertilization-embryo transfer followed by early ultrasound diagnosis of heterotopic CSP and selective embryo reduction performed by transvaginal ultrasound-guided potassium chloride and methotrexate injection in the ectopic gestational sacs., Main Outcome Measure(s): Successful pregnancy outcome., Result(s): An ongoing intrauterine pregnancy with a live birth after successful management of ectopic gestational sacs., Conclusion(s): Triplet heterotopic CSP with two ectopic gestational sacs may occur after IVF-ET and, to our knowledge, this is the first time such a complication has been reported. Ultrasound is the main tool allowing early diagnosis of this condition, and the injection of potassium chloride and methotrexate is a safe and efficacious treatment method. The gynecologist managing early pregnancy should be aware of the possibility of CSP, and patients must be appropriately counseled about the different treatment options., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the influence of specific oocyte morphologic features (morphotypes) on intracytoplasmic sperm injection (ICSI) outcome. The identification of oocyte quality markers is particularly important when a low number of oocytes can be used for IVF., Design: Retrospective analysis., Setting: Medical center., Patient(s): Five hundred sixteen consecutive ICSI cycles. Only couples affected by severe male factor infertility were excluded., Intervention(s): A total of 1,191 metaphase II (MII) oocytes (1-3 per patient) were randomly selected from the cohort of oocytes obtained from each patient and evaluated for morphologic appearance., Main Outcome Measure(s): Fertilization, pronuclear morphology, embryo quality, pregnancy rate., Result(s): There was a presence of vacuoles, abnormal I polar body, and large perivitelline space related to a lower fertilization rate. Pronuclear morphology was effected by the presence of a large perivitelline space, diffused cytoplasmic granularity, and/or centrally located granular area. The latter characteristic also negatively related to day 2 embryo quality. According to the odds ratios obtained for each oocyte morphotype to reach at least one outcome, an MII oocyte morphologic score (MOMS) was calculated. A significant relationship was found between MOMS and female age, female basal FSH, and clinical outcome., Conclusion(s): Morphologic evaluation before ICSI helps to identify MII oocytes with higher developmental potential.

Italian legislation regarding reproductive medicine prohibits embryo storage while allowing cryopreservation of supernumerary oocytes. This study evaluated the effect of fresh oocytes obtained from natural unstimulated cycles on the clinical success rates derived from the use of frozen-thawed (FR-TH) oocytes obtained following ovarian stimulation. For 36 women, intracytoplasmic sperm injection was performed on FR-TH oocytes supplemented by a fresh oocyte, if available, derived from a natural cycle in which gonadotrophin-releasing hormone-antagonist was used for premature LH surge control. The retrieval rate of fresh oocytes was 61.1% and survival rate of FR-TH oocytes was 43.6%. The fertilization rate of fresh and FR-TH oocytes was 70% and 52.5%, respectively. Fifty embryos were transferred, 14 of them developed from fresh oocytes and 36 from FR-TH oocytes. Six pregnancies occurred in 10 cycles in which the embryos developed from fresh and FR-TH oocytes (pregnancy rate 60.0%) and two in 12 patients in whom the embryos were obtained from only FR-TH oocytes (pregnancy rate 16.7%) (P < 0.05). In summary, the data demonstrate that the transfer of embryos derived from oocytes cryopreserved following a previous ovarian stimulation and an embryo developed from a fresh one retrieved in natural cycle ensures an excellent clinical outcome.

Over the last two decades, easier and less expensive stimulation treatments have been largely replaced by more complex and more demanding protocols. Since the mid-nineties, long-term gonadotrophin-releasing hormone agonist stimulation protocols have been widely used. Such lengthy expensive regimens are not free from short- and long-term risks and complications. Mild stimulation protocols reduce the mean number of days of stimulation, the total amount of gonadotrophins used and the mean number of oocytes retrieved. The proportion of high quality and euploid embryos seems to be higher compared with conventional stimulation protocols and the pregnancy rate per embryo transfer is comparable. Moreover, the reduced costs, the better tolerability for patients and the less time needed to complete an IVF cycle make mild approaches clinically and cost-effective over a given period of time. However, further prospective randomized studies are needed to compare cumulative pregnancy rates between the two protocols. Natural cycle IVF, with minimal stimulation, has been recently proposed as an alternative to conventional stimulation protocols in normo- and poor responder patients. Although acceptable results have been reported, further large prospective randomized studies are needed to better evaluate the efficacy of these minimal regimens compared with conventional stimulation approaches.

Italian legislation regarding reproductive medicine limits the number of embryos transferred per attempt to three. Thus, in order to achieve pregnancy, more IVF cycles may be required, generating a need for methods of ovarian stimulation with fewer side effects. The gonadotrophin-releasing hormone (GnRH) antagonists have several advantages in this respect, but there is a debate regarding a possible lower pregnancy rate from resulting cycles. This study evaluated the clinical applicability of GnRH antagonists for ovarian stimulation in young women undergoing intracytoplasmic sperm injection (ICSI) in which only three oocytes can be fertilized. The 200 women treated with GnRH antagonist had a significantly shorter stimulation and lower gonadotrophin consumption, oestradiol concentration, total and mature oocyte recovery as compared with 200 matched controls treated with GnRH agonist. No differences were found between the groups in the number of normal zygotes, total cleaved, transferred and high quality embryos, or in the clinical outcomes. Thus, the previously reported lower pregnancy rate in GnRH antagonist cycles may be related to the oocyte characteristics. Finally, under conditions of oocyte number restriction, the GnRH antagonist-based cycles may be proposed as an efficacious, safe and minimally invasive alternative to GnRH agonist in a standard long protocol.

Objective: To evaluate the impact of uterine artery embolization (UAE) for fibroids on ovarian reserve in women younger than 40 years., Design: Prospective study., Setting: University-based reproductive endocrinology unit., Patient(s): Twenty regularly cycling women aged 33-39 years undergoing UAE for fibroids. All had cycle day 3 FSH levels <10 mIU/mL., Intervention(s): Measurements of serum FSH and E2 levels and of the total ovarian volume and antral follicle number by transvaginal ultrasonography on day 3 of the menstrual cycle preceding UAE and on day 3 of the cycles occurring in months 3, 6, and 12 after UAE., Main Outcome Measure(s): Preprocedural and postprocedural hormone levels, ovarian volumes, and antral follicle numbers., Result(s): There were no significant changes from baseline in the mean day 3 FSH and E2 levels, ovarian volume measurements, and antral follicle numbers measured at 3, 6, and 12 months after UAE., Conclusion(s): Although this study might be not sensitive enough to conclude that UAE for fibroids does not interfere with a woman's ovarian status, these data indicate that in this series of reproductive-aged women UAE did not have short- or mid-term effects on ovarian reserve as assessed by hormonal and sonographic parameters.

Objective: To report a case of permanent amenorrhea associated with endometrial atrophy after uterine artery embolization for symptomatic uterine fibroids., Design: Case report., Setting: Gynecologic clinic of a university hospital., Patient(s): A 44-year-old woman with menorrhagia and anemia caused by multiple fibroids., Intervention(s): Transcatheter bilateral uterine artery embolization with polyvinyl alcohol particles, with hormonal, sonographic, and hysteroscopic follow-up procedures., Main Outcome Measure(s): Serum follicle-stimulating hormone (FSH) and estradiol levels were measured, and sonographic appearance of the ovaries and the endometrium at baseline and 1, 3, 6, and 12 months after treatment were recorded. Hysteroscopy was performed with endometrial biopsy at baseline and 6 months after embolization., Result(s): The patient remained amenorrheic from the procedure. Serial posttreatment measurements of FSH and estradiol levels and repeated ovarian imaging showed no change in ovarian function as compared with baseline. A reduction in endometrial thickness (