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.

Safety of ovarian cryopreservation and transplantation in patients with acute leukemia: a case series.

BACKGROUND: With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through ovarian tissue transplantation remains a major concern for patients with acute leukemias. OBJECTIVE: This study aimed to investigate the safety of performing autologous ovarian tissue transplantation in survivors of acute leukemia. STUDY DESIGN: Clinical, histopathological, and molecular data of 4 women with acute myeloid leukemia and 2 women with acute lymphoblastic leukemia who underwent ovarian tissue cryopreservation and transplantation were analyzed in this case series. Following cryopreservation of 66% to 100% of an ovarian cortex with a slow freezing method, all women received high-dose multiagent alkylating preconditioning chemotherapy for allogeneic hematopoietic stem cell transplantation. Before the ovarian tissue transplantation, (1) antral follicle counts, serum antimüllerian hormone and follicle-stimulating hormone levels were assessed to confirm primary ovarian insufficiency; (2) all recipients were cleared by their hematologist-oncologists; (3) representative cortical strips were screened for leukemia infiltration by histologic (hematoxylin and eosin staining), immunohistochemical (CD3, CD20, CD34, CD68, CD117, CD163, PAX-5, Tdt, lysozyme, and MPO), and molecular marker evaluation (BCR/ABL p190 and AML1/ETO) where appropriate. RESULTS: The median age was 20 years (interquartile range, 15-32) at ovarian tissue cryopreservation. Before undergoing hematopoietic stem cell transplantation, all patients received induction or consolidation chemotherapy that included cytarabine + daunorubicin or Berlin-Frankfurt-Munich-95 protocol and were in remission. The mean serum antimüllerian hormone was 1.9±1.7 ng/mL before ovarian tissue cryopreservation. In all cases, ovarian tissue screening for leukemic cells was negative. Ovarian transplantation was performed laparoscopically with or without robotic assistance, after a median of 74.5 months (interquartile range, 41-120) after ovarian tissue cryopreservation. Ovarian function resumed in all patients after a median of 3.0 months (range, 2.5-4.0), and 2 women had 1 live birth each. The median graft longevity was 35.5 months (interquartile range, 18-57) after ovarian tissue transplantation. After a median follow-up of 51 months (interquartile range, 20-74), all patients remained relapse-free. In 1 patient, the graft was removed during cesarean delivery and was negative for immunochemical leukemia markers. CONCLUSION: Our long-term follow-up demonstrated no evidence of disease relapse after ovarian tissue transplantation in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation. This safety profile may be explained by the fact that these patients are induced into remission by nongonadotoxic induction chemotherapy before undergoing ovarian tissue cryopreservation. We propose that ovarian tissue cryopreservation should not be excluded as a fertility preservation option for young women with leukemia who are due to receive preconditioning chemotherapy before allogeneic hematopoietic stem cell transplantation.

Is Vulvodynia Associated With an Altered Vaginal Microbiota?: A Systematic Review.

INTRODUCTION: Vulvodynia is defined as vulvar pain of at least 3 months' duration, without clear identifiable cause, which may have potential associated factors. It can have a significant impact on women's quality of life due to a combination of physical pain, emotional distress, and limited treatment options. Despite affecting a considerable number of women worldwide, the causes and underlying mechanisms of vulvodynia remain poorly understood. Given the recognized association of the vaginal microbiota with various gynecologic disorders, there has been growing interest in exploring the potential role of the vaginal microbiota in the etiology of vulvodynia. This systematic review aims to evaluate the current literature on the association between the vaginal microbiota and vulvodynia. MATERIAL AND METHODS: A systematic search of multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE, was conducted to identify relevant peer-reviewed studies up to May 12, 2023. The following search terms were used across these databases: "vulvodynia," "vestibulodynia," "vulvar vestibulitis," "microbiome," "microbiota," and "flora." RESULTS: A total of 8 case-control studies were included, the quality of which was assessed using the Newcastle-Ottawa Scale. Data extraction and synthesis were performed using a standardized protocol. In most studies, no major differences were found between the vaginal bacterial composition of women with vulvodynia and that of controls. No specific bacterial taxa were consistently associated with vulvodynia. The relationship between vaginal microbiota diversity and vulvodynia remains to be fully understood. CONCLUSIONS: The role of vaginal microbiota in vulvodynia, if any, remains unclear. Because of the cross-sectional nature of the included studies, it is not possible to make any causal inferences. Further research, using larger and more diverse study populations and advanced sequencing techniques, is necessary to gain a better understanding of the potential relationship between the vaginal microbiota and vulvodynia.

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.

Minimal Invasive Abdominal Sacral Colpopexy and Abdominal Lateral Suspension: A Prospective, Open-Label, Multicenter, Non-Inferiority Trial.

BACKGROUND: Abdominal minimally invasive surgery has become increasingly prominent for the treatment of prolapse. Abdominal sacral colpopexy (ASC) is the gold standard for the treatment of advanced apical prolapse; however, alternative surgical approaches such as the abdominal lateral suspension (ALS) have been developed to improve patient outcomes. This study aims to determine whether ALS improves outcomes compared to ASC in multicompartmental prolapse patients. METHODS: A prospective, open-label, multicenter, non-inferiority trial was conducted in 360 patients who underwent ASC or ALS for the treatment of apical prolapse. The primary outcome was anatomical and symptomatic cure of the apical compartment at 1-year follow-up; secondary outcomes included prolapse recurrence, re-operation rate, and post-operative complications. A 300-patient cohort was subdivided into 200-patients who underwent ALS and 100-patients who underwent ASC. The confidence interval method was used to calculate the p-value of non-inferiority. RESULTS: At the 12-months follow-up, the objective cure rate of the apical defect was 92% for ALS and 94% for ASC (recurrence rates were 8% and 6%, respectively, and the p-value for non-inferiority was <0.01). The mMesh complication rates were 1% and 2% for ALS and ASC, respectively. CONCLUSIONS: This study demonstrated that the ALS technique is not inferior to the gold standard ASC for the surgical treatment of apical prolapse.

The size, number and bilaterality of endometriomas do not affect spontaneous conception chance following surgical removal.

OBJECTIVE: Endometrioma surgery is associated with a reduction in ovarian reserve. However, removal of an endometrioma may increase the likelihood of a spontaneous conception. The objective of this study was to assess the pre-operative and operative variables affecting spontaneous conception following endometrioma surgery. METHODS: Data from 211 women ≤40 years of age who underwent an endometrioma surgery at a university-based infertility clinic between January 2005 and June 2020 were reviewed retrospectively. The main outcome measure was spontaneous clinical pregnancy. We had 84 women with and 127 women without a successful spontaneous conception making up the case and control groups. RESULTS: The median ages of the cases and controls were 27 and 32 years, respectively (p<0.001). The rate of recurrence was significantly lower in the spontaneous conception group when compared to controls (29.8% vs. 52.8%, respectively; p=0.001). Our results showed no differences in the number, size, or side of the endometriomas in both groups. Multivariate logistic regression analysis showed significant independent effects of age (B: -.166, OR {odds ratio}: 0.847, 95% CI {confidence interval}: 0.791-0.907, p<0.001), recurrence (B: -1.030, OR: 0.357, 95% CI: 0.188-0.678, p=0.002), and laparoscopic surgery rather than laparotomy (B: 1.585, OR: 4.879, 95% CI: 1.029-23.133, p=0.046) for spontaneous conception. CONCLUSIONS: The size, number and bilaterality of the endometrioma did not affect the spontaneous conception likelihood following surgical removal. However, increasing age and recurrence are negatively associated with the likelihood of spontaneous conception. Laparoscopic surgery may increase the chance of spontaneous conception when compared to laparotomy.

A Holistic Approach To Oncofertility In A Patient With Rectal Cancer: A Case Report.

OBJECTIVE: Cryopreservation techniques are used to preserve fertility before cancer treatment with gonadotoxic agents. Herein, we report a case of fertility preservation involving a 29-year-old G0P0 woman, married for one year, who was referred to our hospital for fertility preservation before starting rectal cancer treatment. CASE DESCRIPTION: Ovarian tissue and embryo cryopreservation were performed. Before the procedure, ovarian reserve was evaluated, and antral follicle counts were determined. Laparoscopic ovarian tissue cryopreservation was performed from the left side with a lower antral follicle count. Thus, we were able to keep the number of oocytes obtained in the following controlled ovarian hyperstimulation cycle at the highest level. Subsequently, the right ovary was transposed into the lateral wall of the abdomen under the peritoneum. Conventionally controlled ovarian hyperstimulation was initiated on the first postoperative day, depending on the menstrual cycle phase. Intracytoplasmic sperm injection was performed on four mature oocytes obtained, and one embryo was cryopreserved. Controlled ovarian hyperstimulation was initiated on the first postoperative day, and the process was repeated on the seventh postoperative day, yielding a total of seven viable embryos for cryopreservation. CONCLUSIONS: There is usually only one chance of controlled ovarian hyperstimulation in patients requiring a fertility-sparing approach due to malignancy. In the combined technique, performing ovarian tissue resection from the ovary with a lower number of antral follicles can keep the number of oocytes at the highest level in the following controlled ovarian hyperstimulation cycle.

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.

Longitudinal change in serum inflammatory markers in women with tubo-ovarian abscess after successful surgical treatment: a retrospective study.

High levels of serum inflammatory markers are related to extended hospitalisation and more severe disease in the case of tubo-ovarian abscess (TOA). There is scarce information on the serial measurement of inflammatory markers during the postoperative follow-up period of surgically treated TOA. The present study aimed to assess the postoperative longitudinal changes in serum inflammatory markers following surgery for TOA. In this retrospective cohort study, patients who underwent surgery for TOA between January 2010 and March 2020 were reviewed. All inflammatory markers peaked within 48 hours after surgical intervention and then declined with time. The predicted mean of white blood cell count (WBC) to return to normal was 2.5 days (95% CI: 1.0-4.3), which was followed by neutrophil to lymphocyte ratio (NLR) (7.1 days, 95% CI: 4.7-10.8) and C-reactive protein (CRP) (+14 days). In conclusion, serum inflammatory markers increase in the very early post-operative period. While the normalisation period is very slow, it may not be appropriate to use CRP for evaluating the treatment success of TOA surgery. However, WBC and NLR measurements might be useful for follow-up and predicting the need for medical or surgical intervention.Impact statementWhat is already known on this subject? Serum inflammatory markers such as C-reactive protein, white blood cell count, and neutrophil to lymphocyte ratio are usually elevated in women with tubo-ovairan abscess, and high levels of these markers are associated with extended hospitalisation and more severe disease.What do the results of this study add? Our results indicate that the serum inflammatory markers increase and peak within the first 48 hours after surgery for tubo-ovarian abscess. Normalisation of white blood cell count is the fastest in successfully treated patients. However, normalisation of C-reactive protein is slowest, reaching 14 days and might not be as feasible as white blood cell count and neutrophil to lymphocyte ratio in postoperative patient follow-up.What are the implications of these findings for clinical practice and further research? The serum inflammatory markers should be interpreted with caution within 48 hours after surgical treatment for tubo-ovarian abscess. Instead of C-reactive protein white blood cell count, and neutrophil to lymphocyte ratio measurements can be preferred in post-operative follow-up to predict the need for further medical or surgical intervention.

Combined Fertility Preservation Technique before Gonadotoxic Treatments in Cancer Patients.

Although ovarian tissue cryopreservation is still considered as an experimental technique, several authors from around the world have reported successful and promising results. Currently, oocyte cryopreservation seems to be the most feasible technique for fertility preservation when there's some kind of a time constraint in adolescents and adults. However, it has been estimated that a young woman would be expected to have a 94% likelihood of having a live birth with 20 mature frozen oocytes (1). At age 34 years, however, this expectation is decreased to 90% with 20 mature frozen oocytes. In addition to age-related limitations, an immediate obstacle for obtaining oocytes in cancer patients is the fact that only one controlled ovarian hyperstimulation (COH) cycle can usually be performed in these women because of time constraints, yielding a relatively low number of oocytes and/or embryos. For this reason, results from egg donation programs cannot be extrapolated to cancer patients, nor can the quality of oocytes be guaranteed. Hence, a combined fertility preservation technique can be of valuable in increasing the chances of successful future pregnancies following gonadotoxic cancer therapies. Previously, Dolmans et al. (2) suggested that cryopreservation of bilateral ovarian cortex followed by COH is a feasible and safe approach to preserve fertility before gonadotoxic treatment, and that the number of cryopreserved embryos was similar to the controls. We have been offering the option of the combined technique to fertility preservation patients for a couple of years and have performed it in a series of eight candidate patients. All patients had enough time for COH before oncology treatments. We first performed laparoscopic ovarian resection for ovarian tissue cryopreservation and then started COH on postoperative day 0 or 1 in each patient (Table 1). The main point in our findings is that ovarian resection is performed from the side with less antral follicle count of the patients. We suggest that this approach can increase the oocyte yield in a single available COH cycle. The data is limited on the effectiveness of combined technique and more long-term follow-up studies are needed in larger groups with appropriate controls. According to our clinical experience, we believe that combined technique is a valid approach, which is expanding beyond the experimental stage and has become a clinical technique for fertility preservation. We particularly suggest selecting the ovary with a low antral follicle count for wedge resection to increase oocyte yield. The information gathered from large international multicenter reports would encourage physicians to agree that the method should complete the experimental phase and be ready for wider clinical use in female fertility preservation.

Prenatal diagnosis of persistent cloaca accompanied by uterus didelphys: A case report.

Persistent cloaca is a rare abnormality that occurs usually in females and is characterized by direct communication between the gastrointestinal, urinary, and genital structures resulting in a single perineal opening. We report a case of persistent cloaca accompanying uterus didelphys that was diagnosed antenatally with fetal ultrasonography. A gravida 3, para 2, 35-year-old women at 22 weeks of gestation was referred to our hospital with a diagnosis of moderate pyelectasis of the fetal kidneys and fetal diffuse intestinal dilation. Detailed ultrasound scan findings were reported as a small thick-walled septated cystic pelvic mass of 5.2×5.5 cm size seen at the level of the fetal pelvic region. The target sign could not be visualized, it was considered as anal atresia. In the following weeks, the patient, who was evaluated together with meconium on the uterine septum, and monitoring of the neighboring bladder and anal atresia, was diagnosed as having persistent cloaca. Ultrasound findings showed that it could be persistent cloaca accompanying uterus didelphys. The fetus postnatally manifested persistent cloaca. On the first day after vaginal delivery, pelvic ultrasound in the neonatal intensive care unit showed bilateral 2nd-degree hydronephrosis, presacral enlarged bowel loops, uterus didelphis, vaginal septum, direct contact between urethra and vagina, proximal end in the rectum compatible with atresia. On the second day, colostomy was performed. Her renal condition continued to be stable. She is now waiting for definitive surgery for cloaca. Persistent cloaca should be considered in any female fetus presenting with hydronephrosis and a cystic pelvic mass lesion as diagnosed by ultrasound. Prenatal diagnosis allows time for parental counseling and delivery planning at a tertiary hospital for neonatal intensive care and pediatric surgery.