Preservation Of Ovarian Function Research Articles

Preservation of ovarian function using human pluripotent stem cell-derived mesenchymal progenitor cells.

Ovarian reserve diminishes with age, and older women experience a corresponding shift in sex hormone levels. These changes contribute to an age-dependent decrease in fertility and a decline in overall health. Furthermore, while survival rates following cancer treatment have improved for young female patients, a reduction in ovarian function due to the side effects of such treatments can be difficult to avoid. To date, no effective therapy has been recommended to preserve ovarian health in these patients. Mesenchymal progenitor cells (MPCs) are considered a promising option for cell therapy aimed at maintaining fertility and fecundity. Although MPCs derived from human adult tissues are recognized for their various protective effects against ovarian senescence, they are limited in quantity. Consequently, human pluripotent stem cell-derived MPCs (hPSC-MPCs), which exhibit high proliferative capacity and retain genetic stability during growth, have been utilized to delay reproductive aging. This review highlights the impact of hPSC-MPCs on preserving the functionality of damaged ovaries in female mouse models subjected to chemotherapy and natural aging. It also proposes their potential as a valuable cell source for fertility preservation in women with a variety of diseases.

Postoperative Outcomes of Ovarian Preserving Surgery in Premenopausal Women With Adnexal Torsion

ABSTRACT Adnexal torsion, a state of twisted ovaries and adnexa in the infundibulopelvic and tuboovarian ligaments, can occur in benign masses, malignant neoplasms, and normal ovaries. Definitive diagnosis of this condition is surgical, with an incidence rate of 2%–15% in women undergoing surgery for an adnexal mass. This incidence rate is possibly low in its estimation, due to lack of diagnosis sans surgical observation of the condition. This state occurs most frequently in women of reproductive age, although it can occur at any age. A decrease in ovarian blood supply during adnexal torsion may lead to ovarian ischemia, for which a lack of immediate treatment results in reduced ovarian function and fertility damage. Patients with suspicion of this condition are treated via emergent surgery. The aim of this study was to analyze anti-Müllerian hormone (AMH) level changes in premenopausal women, along with possible postoperative complications after surgery preserving ovaries in the case of adnexal torsion. The authors’ intent was to prove the value of conservative surgery in preservation of ovarian function, even in cases with intraoperative findings or postsurgery ovarian color changes. The retrospective study was performed at Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, and included women surgically diagnosed with adnexal torsion between January 2015 and December 2020. Excluded were data for women with no adnexal torsion diagnosis, women who had undergone bilateral ovarian cystectomy, patients lacking AMH data (either prior to or after surgery), and menopausal patients. The study included 71 patients, with 15 in the oophorectomy group and 56 in the ovarian preservation group. Data collected included age, body weight, height, abdominal pain duration, time interval between symptoms and surgery, adnexal mass laterality and size based on the preoperative ultrasounds, and laboratory values (hemoglobin, platelet, white blood cells, and AMH levels). Serum AMH levels were determined both 6 months before surgery and 6–24 months after. Also included were data for postoperative fever/complications and duration of admission. There were 23 patients who had an AMH both before the surgery and postoperatively (19 in the preservation group and 4 in the oophorectomy group). In the ovarian preservation group, 21.0% of patients experienced postoperative fever, with none of the oophorectomy group experiencing similar symptoms. However, all of the fever-stricken patients were discharged with no further complications (ie, pneumonia, surgical site infections, etc). Comparison of both the oophorectomy and ovarian preservation group data showed similar preoperative AMH levels. Postoperatively, serum AMH levels decreased in the oophorectomy group, while slightly increasing in the ovary-preservation group. Despite discoloration and suspected ovarian necrosis, preservation of the ovary preserves ovarian function in reproductive-aged women with adnexal torsion. Only 1 patient undergoing emergent surgery experienced complications. Limitations of the study include its retrospective nature and small sample size when considering patients with emergency surgeries for adnexal torsion diagnoses. In addition, the number of cases with comparable before/after AMH level data available was small. Prospective studies for this area are difficult to perform due to low incidence rates and emergency characteristics. Despite these shortcomings, value can be found in the study data, such as the numerical comparison of ovarian function preservation based on AMH levels before and after surgery. In conclusion, the study found that complications in patients with adnexal torsion were not increased via ovarian-preserving surgery, even with suspected necrosis of the ovary. If preservation of the ovary occurs, the ovarian reserve may not be affected by torsion. For women with cystic masses and adnexal torsion, conservative ovarian surgery (detorsing) can be safely performed to preserve productive potential.

Comparison of the efficacy of Cf-252 neutron intracavitary brachytherapy monotherapy with neutron intracavitary brachytherapy plus external beam radiotherapy in stage IB1 cervical cancer

ObjectiveWe aimed to compare the efficacy of californium (Cf)-252 neutron intracavitary brachytherapy (NIBT) monotherapy with NIBT plus external beam radiotherapy (ERBT) in the treatment of stage IB1 cervical cancer. MethodsFrom May 2006 to March 2014, 38 patients with stage IB1 cervical cancer with negative pelvic lymph node metastasis (NPLNM) who were treated at our hospital were enrolled in this retrospective study. A matched-pair design based on age, hemoglobin level, and tumor histology was used for the analysis. The status of all patients was assessed by the positron emission tomography - computer tomography (PET-CT) scan or the contrast enhancement pelvic CT scan. Cf-252 NIBT was administered for four times, and the total dose at point A was 42–44 Gy. ResultsThe local tumor control rate, overall survival rate, tumor-free survival rate, and late complication incidence rate in the NIBT group were 94.7%, 100%, 94.7% and 0%, respectively, which in the EBRT + NIBT group were 94.7%, 89.5%, 89.5% and 5.26%, respectively. The return of menstruation incidence rate was 36.8% in the NIBT group and 0% in the EBRT + NIBT group. ConclusionThe treatment outcomes in the NIBT group were similar to those in the EBRT + NIBT group for patients with stage IB1 cervical cancer with NPLNM, regular menstruation and at least 3 years of follow-up data. The additional advantage of NIBT monotherapy is the potential preservation of ovarian and endometrial function and hence fertility.

Chinese Expert Consensus on ovarian function and fertility preservation of cervical cancer in pregnancy (2023).

Cervical cancer in pregnancy (CCIP) refers to cervical cancer diagnosed during pregnancy, the most common gynecological malignant tumor. Because of the special physiological changes of CCIP, although preserving ovarian function and fertility is very important, the methods are very limited. There is no guideline or consensus on the preservation methods of ovarian function and fertility in this special period. Therefore, the Committee of Fertility Protection and Preservation of China Association for the Promotion of Health Science and Technology, combined with the Chinese Society of Gynecological Endocrinology affiliated to the International Society of Gynecological Endocrinology, Society Endocrinology Branch of Beijing Institute of Obstetrics & Gynecology, combined with Society on Fertility Preservation affiliated with the Chinese Preventive Medicine Association, organized relevant experts from different disciplines to formulate this consensus, in order to guide ovarian function and fertility preservation of CCIP patients.

Uterine transposition for fertility and ovarian function preservation after radiotherapy

ObjectiveTo evaluate the feasibility of uterine transposition as a method of preserving fertility and ovarian function after pelvic radiation.MethodsThis prospective multicenter observational study included patients with non-gynecologic pelvic cancers who...

High-Dose-Rate Brachytherapy for Vaginal Rhabdomyosarcoma (RMS): Lessons Learned at a Single Institution

Botryoid RMS is a rare pediatric tumor most commonly arising within the vaginal wall of girls under age three. Most patients are successfully treated with low-risk chemotherapy protocols but local treatment is required to minimize risk of local relapse. Intravaginal brachytherapy is an effective local therapy that can minimize sequelae in these very young patients. We reviewed records of all patients with RMS who received intravaginal high-dose-rate brachytherapy from 2010-2022 at a single institution. All were treated with multiagent chemotherapy with or without minor surgical procedures, and had no gross disease prior to intravaginal brachytherapy. All patients underwent CT simulation under anesthesia and optimal-sized cylindrical applicators were chosen based on patient anatomy. Twelve girls, median age 23 months (range 3-33), were treated with daily anesthesia. All were Stage 1 and 92% had Group III disease. A single patient had Group IIA disease based on up-front resection. Early in the series, 5 patients received 21 Gy in 7 fractions according to COG protocol guidelines. Subsequent patients received higher doses of 28-30 Gy in 7-10 fractions. Custom sized cylinders were used with diameters ranging from 1.2-1.6 cm and dose was prescribed to a median depth of 3 mm. Median mean dose to the rectum, bladder, uterus, and bilateral ovaries was 8.7 Gy, 7.2 Gy, 6.9 Gy, and 5.0 Gy, respectively. Median follow-up was 4 years (range 1-10). No acute or late side effects have occurred. At follow-up, three girls were of pubescent age, all three exhibited signs of puberty and two had reached menarche. Three girls (25%) suffered local relapse at a median of 15 months (range 5-16 months) after brachytherapy. One-year and five-year local control rates were 92% (95% CI 54-99%) and 70% (95% CI 32-89%), respectively. All relapses were in patients receiving 21 Gy and two were beyond full dose coverage of brachytherapy at the introitus and in the uterus. Subsequent patients receiving higher doses and full coverage of the vagina have had no local failures. Two of three patients who failed were cured with salvage therapy resulting in one-year and five-year overall survival rates of 100% and 86% (95% CI 33-98%), respectively. Intravaginal high-dose-rate brachytherapy is an excellent option for local control of vaginal RMS with fewer long-term risks than external beam proton therapy or radical surgery. A dose of 28 Gy in 7 fractions prescribed to the entire vagina is necessary for optimal prevention of relapse. Longer follow-up is needed to confirm preservation of ovarian, reproductive, and sexual function.

Long-acting gonadotropin-releasing hormone agonist trigger in fertility preservation cycles before chemotherapy

Oocytes/embryo cryopreservation and ovarian function suppression with gonadotropin-releasing hormone (GnRH) agonists (GnRHas) are two established strategies for preserving fertility in patients with cancer, frequently both being offered to the same woman. As the first injection of GnRHa should be administered before chemotherapy, it is usually performed in the luteal phase of the urgent controlled ovarian stimulation (COS) cycle. The GnRHa flare-up effect on recently stimulated ovaries may cause ovarian hyperstimulation syndrome (OHSS) and this risk may discourage some oncologists to offer an ovarian function preservation method with proven efficacy. We suggest the long-acting GnRHa as an option to trigger ovulation for egg retrieval in oncological patients, whenever ovarian suppression during chemotherapy is planned. We retrospectively analyzed prospectively collected data from all consecutive ovarian stimulation cases in oncological patients for oocyte cryopreservation from 2016 to 2021 in a single academic referral center. The COS was performed according to good clinical practice standards. Since 2020 long-acting GnRHa trigger was offered to all patients for whom ovarian suppression after cryopreservation was planned. All other patients served as controls, stratified for the triggering method used: highly purified chorionic gonadotrophin 10 000 UI or short-acting GnRHa 0.2 mg. Mature oocytes were collected, with the expected maturation rate, in all the 22 cycles triggered with GnRHa. The mean number of cryopreserved oocytes was 11.1 ± 4, with a maturation rate of 80% (57%-100%), versus 8.8 ± 5.8, 74% (33%-100%) with highly purified chorionic gonadotrophin and 14 ± 8.4, 80% (44%-100%) with short-acting GnRHa. No case of OHSS was observed after long-acting GnRHa triggering and by 5 days after egg retrieval most patients had reached luteinizing hormone levels showing suppression. Our preliminary data show that long-acting GnRHa is efficacious in inducing the final oocytes' maturation, reducing OHSS risk and suppressing ovarian function by the start of chemotherapy.

Transumbilical Single-Port Laparoscopic Cystectomy of Giant Ovarian Teratoma

Mature ovarian teratomas are benign germ cell tumors of the ovary, accounting for about 10 % -20 % of ovarian tumors and 95 % of ovarian teratomas. Mature ovarian teratomas are common in young women. They are usually unilateral, slow growing, cystic, mobile, smooth, with little or no ascites. Ovarian cystectomy for benign neoplasms instead of oophorectomy is mandatory for ovarian function preservation. We report a case of a large pelvic teratoma in a 19-year-old adolescent female, approximately 20.7cm×10.5cm in size. The patient's main clinical presentation was mild lower abdominal pain, After transumbilical single-port laparoscopic ovarian cystectomy, the final histopathological report was bilateral ovarian mature teratoma. This case report suggests that transumbilical single-port laparoscopic-assisted in vitro giant ovarian tumor ablation is a safe and feasible surgical approach for patients with benign large adrenal tumors. it effectively combines the advantages of open surgery and laparoscopic resection of large ovarian tumors, which not only protects ovarian function, but also avoids cyst fluid overflow and has significant postoperative cosmetic effects. Nevertheless, this study also had some limitations. First, this was a case report and not a multi-center randomized controlled trial. Second, it included a single patient and the short follow-up data precluded us from deriving any conclusions about the long-term efficacy and safety of this method.

Cost-effectiveness analysis of ovarian function preservation with GnRH agonist during chemotherapy in premenopausal women with early breast cancer.

Is it economically worthwhile to use GnRH agonist (GnRHa) to prevent menopausal symptoms (MS) and protect fertility in premenopausal women with breast cancer (BC) during chemotherapy from the US perspective? It is cost-effective to administer GnRHa during chemotherapy in order to forefend MS in premenopausal patients with BC when the willingness-to-pay (WTP) threshold is $50 000.00 per quality-adjusted life-year (QALY), and to preserve fertility in young patients with BC who undergo oocyte cryopreservation (OC), or no OC, when the WTP thresholds per live birth are $71 333.33 and $61 920.00, respectively. Chemotherapy often results in premature ovarian insufficiency (POI) in premenopausal survivors of BC, causing MS and infertility. Administering GnRHa during chemotherapy has been recommended for ovarian function preservation by international guidelines. Two decision-analytic models were developed, respectively, for preventing MS and protecting fertility over a 5-year period, which compared the cost-effectiveness of two strategies: adding GnRHa during chemotherapy (GnRHa plus Chemo) or chemotherapy alone (Chemo). The participants were early premenopausal women with BC aged 18-49 years who were undergoing chemotherapy. Two decision tree models were constructed: one for MS prevention and one for fertility protection from the US perspective. All data were obtained from published literature and official websites. The models' primary outcomes included QALYs and incremental cost-effectiveness ratios (ICERs). The robustness of the models was tested by sensitivity analyses. In the MS model, GnRHa plus Chemo resulted in an ICER of $17 900.85 per QALY compared with Chemo, which was greater than the WTP threshold of $50 000.00 per QALY; therefore, GnRHa plus Chemo was a cost-effective strategy for premenopausal women with BC in the USA. Probabilistic sensitivity analysis (PSA) results showed an 81.76% probability of cost-effectiveness in the strategy. In the fertility model, adding GnRHa for patients undergoing OC and those who were unable to undergo OC resulted in ICERs of $67 933.50 and $60 209.00 per live birth in the USA, respectively. PSA indicated that GnRHa plus Chemo was more likely to be cost-effective over Chemo when the WTP for an additional live birth exceed $71 333.33 in Context I (adding GnRHa to preserve fertility in young patients with BC after OC) and $61 920.00 in Context II (adding GnRHa to preserve fertility in young patients with BC who cannot accept OC). The indirect costs, such as disease-related mental impairment and non-medical costs (e.g. transportation cost) were not included. All data were derived from previously published literature and databases, which might yield some differences from the real world. In addition, the POI-induced MS with a lower prevalence and the specific strategy of chemotherapy were not considered in the MS model, and the 5-year time horizon for having a child might not be suitable for all patients in the fertility model. When considering the economic burden of cancer survivors, the results of this study provide an evidence-based reference for clinical decision-making, showing that it is worthwhile to employ GnRHa during chemotherapy to prevent MS and preserve fertility. This work was supported by the Natural Science Foundation of Fujian Province [2021J02038]; and the Startup Fund for Scientific Research, Fujian Medical University [2021QH1059]. All authors declare no conflict of interest. N/A.

Laparoscopic ovarian transposition prior to pelvic radiation in young women with anorectal malignancies: a systematic review and meta-analysis of prevalence.

Young women undergoing radiotherapy (RT) for pelvic malignancies are at risk of developing premature ovarian insufficiency. Ovarian transposition (OT) aims to preserve ovarian function in these patients. However, its role in anorectal malignancy has yet to be firmly established. The aim of this review was to determine the effectiveness of laparoscopic OT in preserving ovarian function in premenopausal women undergoing neoadjuvant pelvic RT for anorectal malignancies. MEDLINE, Embase and CENTRAL were systematically searched from inception through to May 2022. Articles were included if they evaluated ovarian function after OT in women with anorectal malignancies undergoing pelvic RT. The primary outcome was ovarian function preservation. The secondary outcome was 30-day postoperative morbidity following OT. From 207 citations, 10 studies with 133 patients with rectal or anal cancer who underwent OT prior to RT were included. Meta-analysis of pooled proportions of preserved ovarian function demonstrated an incidence of 66.9% (95% CI 55.0-79.0%, I2 = 43%). The 30-day postoperative morbidity rate was 1.2% (n = 1). There was heterogeneity in interventions and outcome reporting. Laparoscopic OT in premenopausal patients undergoing pelvic radiation for anorectal malignancies might be an effective technique at reducing ovarian exposure to RT. The meta-analyses must be interpreted within the context of clinical heterogeneity of the included studies. Further studies are required to fully investigate the outcomes of OT in patients undergoing pelvic radiation for anorectal malignancies.

Abstract P5-07-01: Outcomes of multidisciplinary team approach and intensive patient education in young women with breast cancer to improve the rate of fertility preservation

Abstract Background Young breast cancer patients of childbearing age often had to give up their opportunity as women or mothers for cancer treatment. As the survival rate of young breast cancer patients increases with advances in early detection and treatment of breast cancer, interest in issues such as fertility preservation, which have not been satisfied so far, is increasing. This study aims to report the experience of improvement of the fertility preservation rate through a multidisciplinary team approach and systematic patient education for young breast cancer patients. Methods Patients treated with multidisciplinary team approach including surgical, medical oncologist and fertility specialist were included for analysis. Patient were divided into two periods: before and after intensive patient education. Patient education included in-person counseling, hand-out materials, and audiovisual education about ovarian dysfunctions related to cancer treatment and fertility preservation methods. We compared the rate of fertility counseling, preservation between two periods. Also, effect of hormonal receptor status on fertility outcome with pregnancy and birth were analyzed. Results The rates of fertility counseling (39.4% to 58.1%), ovarian function preservation with gonadotropin releasing hormone antagonists (37.8% to 49.7%), and either embryo (0.9% to 5.6%) or oocyte preservation (0 to 7.5%) were significantly increased (all, p< 0.001) after intensive patient education. Pregnancy (9.5% vs 14.2%, p=0.034) and birth rate (7.7% vs 12.2%, p=0.043) were significantly higher with women with negative hormone receptor status. In hormone receptor positive patients, similar pregnancy rates were observed (13.3 ~ 15.4%) in patients who complete 5yearsd of endocrine therapy, stopped endocrine therapy due to side effects, and received no endocrine therapy. Patients with any type of recurrence were not pregnant during follow up period. Patients who stopped endocrine therapy for child plan showed highest rate of pregnancy (56.0%). Multivariable analysis revealed intensive education were highly associated with improved fertility outcomes (OR 3.843 95% CI 2.781–5.311, p=< 0.001) after adjusted for different stage and treatment modality. Conclusion Multidisciplinary team approach with intensive patient education of fertility preservation in young women breast cancer significantly improved fertility preservation attempt. Hormonal receptor status and recurrence were associated with impaired fertility outcomes Citation Format: Young Joo Lee, Hayan Han, Hee Jeong Kim. Outcomes of multidisciplinary team approach and intensive patient education in young women with breast cancer to improve the rate of fertility preservation [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-07-01.

Abstract ED3-3: Oncofertility and other quality of life issues

Abstract The current availability of effective systemic treatment strategies has significantly improved the prognosis of patients with early breast cancer. However, this survival gain is often obtained at the cost of higher toxicity. The increase in life span among breast cancer survivors calls for the need to address both early and late potential adverse effects of anticancer therapies to maximize their quality of life. Among them, the potential gonadotoxicity of anticancer therapies and its implications on fertility and ovarian function need to be discussed with all young patients. According to available guidelines, oncofertility counseling should now be considered mandatory in the care of young women with newly diagnosed cancer. This counselling should focus on the risk of developing treatment-induced premature ovarian insufficiency and on the available techniques to preserve fertility and/or ovarian function. Oocyte/embryo cryopreservation, or ovarian tissue cryopreservation in those not eligible for gamete cryopreservation, are standard strategies to be offered to young patients interested in preserving fertility, i.e. to increase their chances of post-treatment pregnancies. Ovarian suppression with gonadotrophin-releasing hormone agonists (GnRHa) during chemotherapy can be offered to premenopausal patients interested in ovarian function preservation, i.e. to decrease their risk of developing chemotherapy-induced early menopause. Current available data confirm that pregnancy occurring following proper treatment for breast cancer and period of follow-up is safe, both in terms of long-term clinical outcomes for the patients and safety for the babies. However, there is a slightly higher incidence of obstetric and birth complications that require the need for a closer monitoring of these pregnancies. Beyond fertility and pregnancy-related issues, a long-term follow-up of young women with breast cancer by the oncofertility unit is recommended for improving the management of other additional gynecological-related issues faced by these women. Among them, contraception should be considered during active treatment and in the follow-up of women who do not wish to get pregnant. Moreover, in the current era of more complex endocrine therapy approaches with a major negative impact on the quality of life of premenopausal patients with breast cancer, it is essential to properly and proactively care about their treatment-related side effects. Among them, menopause related-symptoms and sexual dysfunction may be better managed by implementing a close collaboration between oncologists and gynecologists within the oncofertility unit. Citation Format: Matteo Lambertini. Oncofertility and other quality of life issues [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED3-3.

Human Pluripotent Stem Cell-Mesenchymal Stem Cell-Derived Exosomes Promote Ovarian Granulosa Cell Proliferation and Attenuate Cell Apoptosis Induced by Cyclophosphamide in a POI-like Mouse Model.

Premature ovarian insufficiency (POI) is a complex disease which causes amenorrhea, hypergonadotropism and infertility in patients no more than 40 years old. Recently, several studies have reported that exosomes have the potential to protect ovarian function using a POI-like mouse model induced by chemotherapy drugs. In this study, the therapeutic potential of exosomes derived from human pluripotent stem cell-mesenchymal stem cells (hiMSC exosomes) was evaluated through a cyclophosphamide (CTX)-induced POI-like mouse model. POI-like pathological changes in mice were determined by serum sex-hormones levels and the available number of ovarian follicles. The expression levels of cellular proliferation proteins and apoptosis-related proteins in mouse ovarian granulosa cells were measured using immunofluorescence, immunohistochemistry and Western blotting. Notably, a positive effect on the preservation of ovarian function was evidenced, since the loss of follicles in the POI-like mouse ovaries was slowed. Additionally, hiMSC exosomes not only restored the levels of serum sex hormones, but also significantly promoted the proliferation of granulosa cells and inhibited cell apoptosis. The current study suggests that the administration of hiMSC exosomes in the ovaries can preserve female-mouse fertility.

Gonadotropin-releasing hormone agonist for the preservation of ovarian function in survivors of haematopoietic stem cell transplantation for haematological diseases

ObjectiveAdministration of GnRH agonist (GnRHa) prior to chemotherapy may decreases the risk of gonadal dysfunction in patients with tumors. However, relevant data in haematopoietic stem cell transplantation (HSCT) recipients has not yet been established. Hence, the present study was designed to evaluate the clinical efficacy of GnRHa cotreatment prior to myeloablative regimens on ovarian protection in female survivors of HSCT for haematological diseases.Patients and methodsEligible patients were divided into a GnRHa group and a control group. Medical records regarding age at HSCT; diagnosis/indication for HSCT; pre- and posttransplantation serum sex hormone levels; menstruation and perimenopausal symptoms after HSCT were collected and compared. The primary and secondary outcome was the incidence of premature ovarian insufficiency (POI) symptoms associated with hypoestrogenism.ResultsA total of 330 patients were enrolled in the study: 19 patients were lost to follow-up, and clinical information was obtained in 311 patients. There was no significant difference in the primary outcome of follow-up between the two groups (78.50% [84 of 107] for the GnRHa group versus 83.33% [170 of 204] for the control group). The adjusted relative risks (RR) and 95% confidence interval (CI) were 1.19 and 0.73–1.93 (P = 0.487). Among patients who received cotreatment with GnRHa, 62.62% (67 of 107) complained of perimenopausal symptoms, which was significantly lower than the 74.51% (152 of 204) in the control group (adjusted RR: 1.46, 95% CI: 1.04–2.06, P = 0.031).ConclusionGnRHa cotreatment may not decrease the POI rate in HSCT survivors. However, it may reduce perimenopausal symptoms in this population, suggesting a potential benefit of GnRHa in clinical practice and warrant further researches.

Blue to Pink in 10 Minutes: Fallopian tube and Paratubal Cyst Torsion. Case Presentation and Demonstration of Dissection Principles

<h3>Study Objective</h3> To demonstrate immediate changes in fallopian tube appearance upon detorsion. To encourage fallopian tube preservation in circumstances of torsion, in patient at low risk of cancer and desiring future fertility. To demonstrate principles of robotic dissection and cooperation with bedside assistant. <h3>Design</h3> Video case report. <h3>Setting</h3> Tertiary Gynecologic Oncology Center. <h3>Patients or Participants</h3> 26yo desiring future fertility presenting with pelvic mass and subacute pain. <h3>Interventions</h3> Da Vinci Xi robotic surgery. <h3>Measurements and Main Results</h3> Dissection of fallopian tube from paratubal cyst and detorsion of fallopian tube took approximately 10 minutes. Immediate improvement in fallopian tube perfusion resulted in change in color from blue to pink. Since fallopian tube had been stretched, it was twice longer than usual. Fallopian tube, was attached to the ovary to keep fimbria in close proximity. Safe dissection principles including appropriate selection of instruments, creation of three-dimensional anatomy, defining surgical planes and organ borders, traction-countertraction, adjusting dissection direction to tissue response, active involvement of bedside assistant are discussed and demonstrated. <h3>Conclusion</h3> Fallopian tube detorsion should be attempted even in situations of significant change in tissue color when preservation of fertility is desired, and risk of cancer is low. Fixation of fallopian tube or ovary to prevent repeat torsion is controversial. Studies report preservation of ovarian function in 90% of detorsion cases. Tissue falling apart during handling suggests necrosis and requires removal, as it may result in peritonitis and sepsis.

Gonadotropin-releasing hormone agonist protects ovarian function in young patients with ovarian malignancy undergoing platinum-based chemotherapy: A prospective study.

We aimed to ascertain the effectiveness of gonadotropin-releasing hormone (GnRH) agonist co-therapy for the preservation of ovarian function in patients with ovarian malignancy who underwent unilateral salpingo-oophorectomy and platinum-based chemotherapy. We enrolled 158 patients with ovarian malignancy who underwent fertility preservation surgery and postoperative platinum-based chemotherapy between January 2018 and December 2020. Patients were divided into two groups based on the use of GnRH agonist (GnRHa) during chemotherapy. Two patients withdrew from the study. Laboratory tests (serum follicle-stimulating hormone [FSH], serum luteinizing hormone [LH], and serum anti-Müllerian hormone [AMH]) were performed pre-chemotherapy and one year post-chemotherapy. Data on menstruation resumption, perimenopausal symptoms (modified Kupperman Menopausal Index [KMI]), health-related quality of life (Medical Outcomes Study Short Form-36 [MOS SF-36]), and obstetric outcomes were collected. One year post-chemotherapy, the serum AMH level in the GnRHa group was higher than that in the control group (P<0.001), while the serum FSH and FSH/LH levels in the GnRHa group were lower than those in the control group (P<0.001). The mean period from last chemotherapy to menstrual resumption was 3.86 and 5.78 months in the GnRHa and control groups (P<0.001), respectively. The rate of menstrual resumption post-chemotherapy was 93.5% and 82.3% in the GnRHa and control groups (P<0.05), respectively. GnRHa co-administration during chemotherapy reduced the likelihood of low AMH levels post-chemotherapy and was significant in the multivariate analysis (P<0.05). The modified KMI scores and MOS SF-36 scores were better in the GnRHa group than in the control group (both P<0.001). GnRHa protects ovarian function during platinum-based adjuvant chemotherapy in young patients with ovarian malignancy. This study provides a therapeutic reference for gynecologists, especially for those in economically and medically underdeveloped areas. Chinese Clinical Trial Registry (chiCTR1800019114; October 26, 2018; http://www.chictr.org.cn/index.aspx).

Outcomes of ovarian transposition in cervical cancer; an updated meta-analysis

BackgroundCervical cancer is the most common indication for ovarian transposition in reproductive-age women. Ovarian transposition should be performed in premenopausal women undergoing pelvic irradiation to preserve ovarian function, and prevent early menopause. As women become more knowledgeable about their fertility options, it is still unclear who will benefit from the intervention. We updated our previous meta-analysis of ovarian function preservation, symptomatic ovarian cysts, and metastases to the transposed ovaries following ovarian transposition in cervical cancer patients to further guide current clinical practice.MethodsA systematic search of Medline, Embase, Web of Science, and The Cochrane Library databases, dating from January 1980 to July 2021, was conducted. We computed the summary proportions of women who had ovarian function preservation, non-ovarian cyst formation and metastases to the transposed ovaries following ovarian transposition by random-effects meta-analysis and we explored study heterogeneity by type of radiotherapy.ResultsThere were 29 publications reporting on 1160 women with cervical cancer who underwent ovarian transposition. In the group that underwent surgery alone, 91% of the women had preserved ovarian function (95% CI 83–100), 89% (95% CI 80–99) of women who did not develop ovarian cysts, and 99% (95% CI 1–5) of women who did not suffer metastases to the transposed ovaries. In the surgery ± brachytherapy (BR) group, the proportion of women with the preserved ovarian function was 93% (95% CI 76–113), 84% (95% CI 69–103) of women who did not develop ovarian cysts, and 99% (95% CI 82–120) of women who did not suffer metastases to the transposed ovaries. In the external beam pelvic radiotherapy (EBRT) ± BR ± surgery group, the proportion of women with the preserved ovarian function was 61% (95% CI 55–69), and 95% (95% CI 85–107) of women who developed ovarian cysts. There were no metastases to the transposed ovaries in that group.ConclusionsIn women with cervical cancer, ovarian transposition offers a significant preservation of the ovarian function. Despite an expected incidence of ovarian cyst formation, it carries almost no risk for metastases to the transposed ovaries.

Ovarian Auto-Transplantation of Cryopreserved Tissue on Muscle Surface Compared With Subrenal Capsular in Rats

Fertility protection and ovarian function preservation are important to those undergoing radiation therapy to fight female reproductive cancers. The aim of this study was to explore a new ovarian transplantation position, the surface of thigh muscle, which was biceps femoris muscle in rats. We hypothesized that this procedure was comparable to traditional subrenal capsular transplantation and realized a normal ovarian function. The ovarian tissue, after cryopreservation, were transplanted to surface of biceps femoris muscle by suturing. Histologic examination indicated that the transplanted tissues would survive and support a lower level of follicle growth compared with subrenal capsular (17 ± 2.6 vs 8.9 ± 4; P=.0018). According to weight gaining record, muscle surface transplantation supported appropriate weight gain although the β-estradiol levels did not completely recover. This new procedure could support a basic normal estrous cycle. Ovarian transplantation through this procedure partly rebuilt ovarian function, which was more likely to be an alternative way for those not suitable for subrenal capsular transplantation.

Laparoscopic Ovarian Transposition with Extraperitonealization of the Infundibulopelvic Ligament for Cervical Cancer in Ten Steps

Preservation of ovarian function is important for the physical and psychosexual well-being of young patients with cancer. Patients with pelvic malignancies such as cervical or rectal cancer planned for radiotherapy may benefit from ovarian transposition with the aim of moving the ovaries outside the radiation field.1 Different surgical techniques have been reported previously.2,3 With the present video, we aim to standardize the surgical technique of laparoscopic ovarian transposition in ten steps. We present the case of a 30-year-old nulliparous woman diagnosed with grade 3 squamous cell cervical carcinoma having a largest tumor diameter of 41 mm on magnetic resonance imaging (MRI) scan. The tumor was staged as FIGO 2018 stage IIIC1r with a common iliac lymphadenopathy reported on both MRI and positron emission tomography (PET)/computed tomography (CT) scan. The multidisciplinary team recommended exclusive chemoradiation extended to paraaortic area. The patient underwent laparoscopic bilateral salpingectomy and bilateral ovarian transposition with extraperitonealization of the infundibulopelvic ligament. The procedure was divided into the following ten steps: division of uteroovarian ligament, incision of lateral pelvic peritoneum, identification of ureter, incision of medial pelvic peritoneum, skeletonization of the infundibulopelvic ligament, retroperitoneal tunnel in paracolic gutter, creating the window (as high as possible), mobilization of the ovary without torsion, intraperitonealization of the ovary, and fix ovary with clips (Fig. 1). Surgical time was 30 min, with minimal estimated blood loss. No intra- or postoperative complication was recorded. The patient started radiotherapy 14 days after the procedure. In conclusion, we showed that laparoscopic ovarian transposition in cervical cancer before radiotherapy can be standardized in ten steps with encouraging perioperative results, making it an easily reproducible procedure. Ovarian function is reported to be preserved in 62–65% of cases undergoing ovarian transposition and radiation therapy.4,5Fig. 1Laparoscopic view of right ovary transposed below the liver edge after extraperitonealization of the infudibulopelvic ligament

Functional and structural assessment of the possible protective effect of platelet-rich plasma against ischemia/reperfusion-induced ovarian injury in adult rats.

This study aimed to evaluate the possible protective effect of platelet-rich plasma (PRP) on ischemia reperfusion (I/R)-induced ovarian injury in a rat model. Forty adult female albino rats were randomly assigned to four groups: control, ischemia, I/R, and I/R + intraperitoneal PRP. Induction of ischemia was done by bilateral ovarian torsion for 3 h, while reperfusion was done by subsequent detorsion for another 3 h. PRP was injected 30 min before detorsion. Histological assessment and measurement of ovarian anti-Mullerian hormone (AMH) were done to assess the degree of tissue damage and the remaining ovarian reserve. Ovarian malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured to evaluate the oxidant-antioxidant balance. Tumor necrosis factor-α (TNF-α) was measured to assess degree of inflammation. Immunohistochemical assessment of ovarian vascular endothelial growth factor-A (VEGF-A) was also done. PRP treated I/R group revealed a significant decrease in MDA (P = 0.007), TNF-α (P = 0.001), and a significant increase in TAC (P = 0.001) and VEGF-A (P = 0.003) in comparison to the untreated I/R group. Furthermore, limited vascular congestion and inflammatory infiltration were observed after PRP treatment. However, no significant difference was detected in AMH after PRP treatment. Our results denoted that PRP may help in preservation of ovarian function and structure during surgical conservative detorsion of the torsioned ovary. These protective effects could be attributed to its ability to reduce oxidative stress, inflammation and also to its high content of growth factors especially VEGF.