Ovarian tissue cryopreservation and transplantation as a natural means to delay menopause.

Ovarian tissue cryopreservation and transplantation (OTCT) offers hope for preserving fertility and endocrine functions in patients undergoing gonadotoxic treatments. Advancements in techniques for the procedure have transformed OTCT from an experimental procedure into a viable option. There is a growing interest in utilizing OTCT to delay menopause and alleviate associated health issues. Menopausal transition affects women globally, leading to symptoms and long- term health risks. OTCT has the potential to restore endocrine functions, reducing menopause-related symptoms while mitigating health consequences such as osteoporosis and cardiovascular diseases. Although the use of OTCT for delaying menopause is not clinically proven, the discussion around shows potential for future utilization. In essence, the remarkable advancements in OTCT have bestowed upon us the ability to safeguard fertility and sustain the delicate endocrine functions of the ovaries. However, it is the tantalizing prospect of utilizing this technique to postpone menopause and alleviate its associated symptoms that truly captivates the imagination. Further research is imperative to substantiate the clinical efficacy of OTCT; nonetheless, its potential in menopausal therapy is both promising and warrants comprehensive exploration. This review highlights advancements and the feasibility of OTCT to postpone menopause as an alternative approach to currently used conventional menopause therapy methods.

Maximizing Success: An Overview of Optimizing the Ovarian Tissue Transplantation Site.

Ovarian tissue cryopreservation and transplantation (OTCT) has emerged in recent years as a potential method for reversing abnormal endocrine and reproductive functions, particularly in patients receiving gonadotoxic cancer treatments having longer survival rates. From its first rodent experiments to human trials, OTCT has evolved tremendously, opening new windows for further utilization. Since then, significant progress has been achieved in terms of techniques used for surgical removal of the tissue, optimal fragment size, freezing and thawing procedures, and appropriate surgical sites for the subsequent reimplementation of the graft. In addition, various approaches have been proposed to decrease the risk of ischemic injury, which is the leading cause of significant follicle loss during neo-angiogenesis. This review aims to discuss the pros and cons of ovarian and retroperitoneal transplantation sites, highlighting the justifications for the viability and efficacy of different transplantation sites as well as the potential advantages and drawbacks of retroperitoneal or preperitoneal area.

Random start ovarian stimulation before gonadotoxic therapies in women with cancer: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian stimulation (CSOS) in cancer patients before gonadotoxic treatment. The final analytical cohort encompassed 688 RSOS and 1076 CSOS cycles of cancer patients before gonadotoxic treatment. Eleven studies were identified by database searches of MEDLINE, Cochrane Library and cited references. The primary outcomes of interest were the number of oocytes and mature oocytes collected, the number of embryos cryopreserved and the metaphase II (MII)-antral follicle count (AFC) ratio. The studies were rated from medium to high quality (from 6 to 9) according to the Newcastle-Ottawa Quality Assessment Scale. The two protocols resulted in similar numbers of oocytes collected, MII oocytes, embryos available for cryopreservation and comparable MII-AFC and fertilization rates. The duration of ovarian stimulation was longer (standardized mean difference [SMD] 0.35, 95% CI 0.09 to 0.61; P = 0.009) and gonadotrophin consumption was higher (SMD 0.23, 95% CI 0.06 to 0.40; P = 0.009) in RSOS compared with CSOS. This systematic review and meta-analysis show that the duration of stimulation is longer, and the total gonadotrophin consumption is higher in cancer patients undergoing RSOS compared with those undergoing CSOS, with no significant effect on mature oocyte yield.

Investigation of the risk factors associated with osteoporosis in postmenopausal women

Objective: Osteoporosis is a substantial global public health issue. The objective of this study was to evaluate the risk variables associated with osteoporosis among patients seeking care at an outpatient menopausal clinic in a tertiary university hospital. Material and Methods: In this retrospective, cross-sectional study postmenopausal women who attended the outpatient menopause clinic of Baskent University Hospital between June 01, 2014, and August 31, 2015, were enrolled. Patients' datasheets were reviewed and data including age, body mass index, parity, duration and age of menopause, history of smoking and oral contraceptive pills (OCPs) use, natural or surgical menopause, and calcium-containing food consumption were collected through a standardized questionnaire. Bone mineral density (BMD) was measured at the femur neck and lumbar spine by dual energy X-ray absorptiometry. Results: A total of 1,148 women with a mean age of 53.5±6.7 years, mean duration of menopause 7.1±6.2 years and mean age of menopause 46.3±5.1 years were identified. Of these, 235 (20.5%) were diagnosed as having osteoporosis. The average femur and lumbar T-values showed a decrease in normal weight patients compared to overweight, obese, and morbidly obese patients (F=22,337, p<0.001 and F=50,195, p<0.001, respectively). The mean femur T-values were higher in participants who used OCPs, regularly consumed a calcium-rich diet, and performed regular physical activity (p<0.05, p<0.01 and p<0.05). Positive correlations were noted between giving birth and femur T-values (r=0.065, p=0.027), between natural menopause and lumbar T-values (r=0.060, p=0.043), and between consuming a calcium-rich diet and femur T-values (r=0.087, p=0.003 and r=0.064, p=0.031, respectively). Conclusion: Using OCPs, lifelong physical activity, and a healthy diet rich in calcium are important factors for the prevention of low lumbar spine and femoral BMD and by implication, osteoporosis.

Neurovascular bundle-sparing ventral clitoroplasty in adult patients: description of the technique and long-term outcome on clitoral functions

Objective: To describe the technique and assess long term effects of neurovascular bundle-sparing adult clitoroplasty on clitoral functions in patients. Material and Methods: A case series study enrolling three patients diagnosed with adult clitoromegaly who underwent neurovascular bundle-sparing ventral clitoroplasty operation. All of the patients were examined at the first, third, sixth, twelfth and twenty-fourth months post-operatively to evaluate clitoral functions. Results: Three patients diagnosed with adult clitoromegaly, aged 17, 21 and 24 years, were enrolled in the study. The primary complaint of all patients was unpleasant enlarged appearance and hypersensitive clitoris. Mean calculated clitoral index was 143 mm2, 150 mm2, and 120 mm2. Operation time was 90, 140 and 120 minutes, respectively. No major complication occurred during the operation but moderate ecchymosis and edema of the vulva occurred in all patients, lasting up to three weeks. On follow up examination, partial sensorial loss was noted at the first month in one patient, which completely resolved by the third month and beyond. Two patients who were sexually active reported that they were very comfortable with intercourse and cosmetic appearance. No clitoral enlargement or pain were reported by patients through the 24-month follow up period. Conclusion: Neurovascular bundle-sparing ventral clitoroplasty is a safe and cosmetically acceptable procedure, which effectively preserves the neurovascular bundle and long-term clitoral functions.

Transabdominal ultrasound-guided oocyte retrieval for oocyte cryopreservation using a vaginal probe: a comparison of applicability, effectiveness, and safety with conventional transvaginal approach.

PURPOSE: We aimed to compare the feasibility, effectiveness, and safety of transabdominal ultrasound-guided oocyte retrieval (TUGOR) using a vaginal probe and traditional vaginal approach in virgin patients undergoing oocyte cryopreservation. METHODS: A total of 116 virgin patients who underwent transabdominal ultrasound-guided oocyte retrieval using a vaginal ultrasound probe and 33 patients matched for BMI, antral follicle count, age, day 3 FSH, estradiol, and AMH who underwent vaginal approach were enrolled. Mean number of total oocytes collected, mean number of cryopreserved MII oocytes, duration of the procedure, duration of stimulation, mean gonadotropin consumption, mature oocyte ratio, and a modified follicle-oocyte index were compared between the groups. RESULTS: No statistical difference was found between the groups in mean number of follicles > 12 mm (4.62 ± 4.54 vs. 5.44 ± 4.52), mean number of oocytes collected (4.44 ± 4.14 vs. 5.33 ± 4.52), mean number of cryopreserved MII oocytes (4.01 ± 3.67 vs. 4.53 ± 4.13), mean duration of the procedure (12.4 ± 1.2 vs. 13.4 ± 1.6 min), mean days of stimulation (8.05 ± 1.91 vs. 8.35 ± 1.72 days), mean gonadotropin consumption (1507.9 ± 475.3 vs. 1571.74 ± 404.6 units), mature oocyte ratio (0.78 ± 0.24 vs. 0.82 ± 0.26), and modified follicle oocyte index (0.86 ± 0.63 vs. 0.84 ± 0.19). In the TUGOR group, superficial epigastric artery injury occurred in two patients and resolved spontaneously. CONCLUSION: Transabdominal oocyte retrieval using a vaginal ultrasound is a safe, effective, and feasible method of oocyte retrieval in some selected patient groups.

Laparoscopy versus open surgery for the surgical management of tubo-ovarian abscess (TOA). Is there a beneficial impact of early endoscopic intervention in terms of fertility rates?

OBJECTIVES: To compare success rates and complications in women undergoing laparoscopic versus open surgical management of tubo-ovarian abscess. We further examined whether early laparoscopic intervention has any impact on pregnancy rates in a subgroup of infertile patients following frozen-thawed embryo transfer. MATERIAL AND METHODS: Hospital records of 48 patients diagnosed with TOA between January 2015 and December 2020, who underwent surgical intervention or received only medical treatment were analyzed. All patients were hospitalized, and parenteral antibiotics were commenced on admission initially. Laparoscopic or open surgery was performed within 48 hours course of intravenous antibiotherapy (early intervention) or later according to the clinical findings and antibiotherapy response. RESULTS: Of 48 patients with TOA, 18 (37.5%) underwent laparoscopic and 30 (62.5%) underwent open surgical intervention. The median postoperative hospital stay was shorter (4.5 days vs 7.5 days, respectively; p = 0.035), and postoperative opioid analgesic requirement was lesser in the laparoscopy group compared to open surgery group (22% vs 53%, respectively; p = 0.034). Intra- and post-operative complication rates were similar between the groups. Of these 48 patients, seven were diagnosed to have TOA following oocyte retrieval, and four of these conceived with frozen thawed embryo transfer all of whom underwent laparoscopic surgery within 48 hours of diagnosis. CONCLUSIONS: Minimal invasive surgery should be preferred even in the presence of severely adhesive and inflammatory TOA in order to improve postoperative outcomes. Moreover, early laparoscopic intervention may be considered in infertile patients with an aim to optimize pregnancy rates in a subsequent frozen-thawed embryo transfer.

Ongoing pregnancy and healthy live births following very short ovarian stimulation of incidentally observed big antral follicles in oligoamenorrheic patients with extremely decreased ovarian reserve.

In the present case series our aim is to present seven patients with extremely decreased ovarian reserve and oligomenorrhea, conceived with in vitro fertilization following a very short ovarian stimulation of incidentally detected big antral follicles. The study included women pursuing in vitro fertilization due to premature ovarian failure risk. When an incidental growing antral follicle was detected under ultrasound, immediate ovarian stimulation was initiated if the blood estradiol, luteinizing hormone and progesterone levels were correlated. Serum anti-Mullerian hormone measurements of all patients were consistent with extremely diminished ovarian reserve (ranged between 0.01 and 0.09ng/ml) and FSH levels varied between 13-104IU/l. The mean stimulation length ranged between 2-4 days. A total of 8 oocytes were retrieved; 6 MII, 1 GV and 1 degenerated. All 6 MII oocytes were fertilized with intracytoplasmic sperm injection. Two patients conceived after fresh embryo transfer, whereas the one conceived following frozen thawed embryo transfer. The ongoing pregnancy rate was 50% per transfer, and two of them resulted in a healthy live birth. In conclusion, close monitoring of oligoamenorrheic infertile patients who are at high risk of imminent ovarian failure using ultrasound and blood hormone levels is very important. Albeit low, the possibility of having a healthy pregnancy following "a very short ovarian stimulation" in such a specific patient group is emphasized.

Comparison of Oocyte and Embryo Quality Between Random Start and Controlled Ovarian Stimulation Cycles in Cancer Patients Undergoing Fertility Preservation.

Conventional assisted reproductive technology (ART) cycles may delay cancer treatment and compromise survival, and also increase patients' psychological burden as a result of delayed chemotherapy. The aim of this study was to compare the success rates of random start and conventional start GnRH antagonist protocols in terms of oocyte and embryo outputs in cancer patients. Data of 111 patients with a newly diagnosed cancer who underwent ART for fertility preservation at a university-based infertility clinic between January 2010 and September 2019 were reviewed. The study group underwent random start controlled ovarian hyperstimulation (RS-COH) and the control group underwent conventional start COH (CS-COH). The main outcome measures were the number of total oocytes, MII oocytes, and embryo yield. A total of 46 patients (41.5%) underwent RS-COH and 65 (58.5%) underwent CS-COH. Baseline characteristics were similar between the groups. The most common cancer type in both groups was breast cancer (60.9% vs. 52.3%, respectively). The median duration of stimulation was significantly longer in RS-COH than in CS-COH (12 vs. 10 days; P = 0.005). The median number of MII oocytes was significantly higher in RS-COH than in CS-COH (7 vs. 5 oocytes, respectively; P = 0.020). The MII/AFC ratio was significantly higher in the RS-COH group compared to the CS-COH group (74% and 57% respectively; p = 0.02). In the linear regression analyses, RS-COH protocol did not have a significant impact on MII/AFC (standardized ß coefficient - 0.514; P = 0.289 {adjusted R2 for the model = 0.779}), oocyte yield (standardized ß coefficient - 0.070; P = 0.829 {adjusted R2 for the model = 0.840}), and MII rate (standardized ß coefficient - 0.504; P = 0.596 {adjusted R2 for the model = 0.271}). In conclusion, RS-COH protocol is as effective as CS-COH protocols for fertility preservation in cancer patients.

The efficacy of dydrogesterone use to suppress premature luteinizing hormone surge on cycle outcomes in controlled ovarian stimulation

Objective: Progestins are used as an alternative to gonadotropin releasing hormone (GnRH) antagonists to suppress premature luteinizing hormone (LH) surge and a flexible protocol has been defined recently. The aim of this study was to compare the efficacy of flexible protocols with dydrogesterone and GnRH antagonist in suppressing LH surge. Material and Methods: This retrospective, case-control study, was conducted in an infertility unit of a tertiary university hospital. A daily dose of 40 mg dydrogesterone was compared with GnRH antagonist (GnRHant) in controlled ovarian hyperstimulation cycles between July 2018 and July 2019. Dydrogesterone was started when the leading follicle was 12 mm or serum estradiol was over 300 pg/mL. A subgroup analysis of poor responder patients was also performed. Results: In total there were 105 subjects aged between 23 and 41 years, 52 in the dydrogesterone group and 53 in the GnRHant group. Duration of pituitary suppression was longer in dydrogesterone group. Premature ovulation was observed in 11.5% (6/52) and 0% in the dydrogesterone and GnRHant groups, respectively. However, collected oocyte counts and metaphase II oocyte counts were found to be similar between the groups. The six patients with premature ovulation were in poor responder subgroup. Conclusion: Dydrogesterone can be used as an alternative to antagonist regimen in patients where embryo transfer is not planned in the same cycle. However, flexible regimen may not be appropriate in patients with diminished ovarian reserve, as advanced follicular maturation and delayed suppressive effect of oral progesterone may cause premature ovulation. Randomized controlled trials in particular patient groups are required to determine the most effective minimum dose and time of application to ensure treatment success.

Transabdominal ultrasound guided oocyte retrieval using vaginal ultrasound probe: Definition of the technique.

PURPOSE: To define whether transabdominal ultrasound guided oocyte retrieval (TUGOR) is a feasible, effective and safe method. METHODS: A total of 64 patients who underwent TUGOR in a tertiary referral university hospital in vitro fertilization (IVF) clinic were enrolled. Indications, total number of oocytes collected, total number and percentage of mature oocytes, duration of procedure, complication rates and total number of fertilized oocytes were assessed. RESULTS: The indications for TUGOR were as follows; virgin women with decreased ovarian reserve who opted fertility preservation (n = 52, 81.1%), Ewing Sarcoma (n = 1, 1.56%), breast cancer (n = 4, 6.2%), lymphoma (n = 1, 1.56%) endometrioma (n = 1, 1.56%), immature teratoma of the ovary (n = 1, 1.56%), multiple large uterine fibroids (n = 2, 3.1%), adnexal transposition due to bowel surgery (n = 1, 1.56%) and Mayer Rokitansky Küster Hauser Syndrome (n = 1, 1.56%). Total number of oocytes retrieved and mean number of oocytes collected were 315 and 4.92 ± 1.7 (range 1-21), respectively. The mean duration of the procedure was 12.4 ± 1.2 min. The number and percentage of mature oocytes were 272 and 86.3%, respectively. A total of 14 embryos were frozen in four patients and one blastocyst transfer was performed ending up with live birth. Superficial epigastric artery injury occurred in two patients and resolved spontaneously. No oocyte was retrieved in five patients with single growing follicle in the first attempt. CONCLUSION: TUGOR is a feasible, effective and safe method of oocyte retrieval for the purpose of fertility preservation or in patients with inaccessible ovaries via transvaginal route undergoing IVF.