Asprosin-induced alterations in female rat puberty and reproductive hormonal profiles.

OBJECTIVE: To investigate the comprehensive effects of daily chronic asprosin administration on various pubertal and reproductive parameters in female rats. This study aims to elucidate the role of asprosin in regulating the onset of puberty and its influence on hormonal profiles and ovarian histology. METHODS: Asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg daily for eight weeks. Hormonal assays and histological analyses were performed to evaluate the effects of asprosin on the onset of puberty and reproductive function. RESULTS: Daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays revealed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. CONCLUSIONS: Role of adipokines in regulating puberty and reproductive function has increasingly gained recognition. This study aimed to provide the first comprehensive examination of the effects of daily chronic asprosin administration on pubertal and reproductive parameters in female rats. Utilising hormonal assays and histological analyses, asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg, daily, for eight weeks. Our findings revealed that daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays showed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. These results provide new insights into asprosin's role in advancing the age of first oestrus and modulating hormonal profiles, thereby offering potential benefits to the female reproductive system.

Factors associated with successful intraoperative oocyte retrieval for fertility preservation during open pelvic surgery for gynecologic indications.

OBJECTIVE: The study investigated factors associated with successful intra-operative oocyte retrieval for fertility preservation during transabdominal gynecologic surgery. STUDY DESIGN: A total of 29 patients who underwent intraoperative oocyte retrieval during staging surgery at a single academic hospital from May 2014 to August 2022 were enrolled in this study, and their outcomes were analyzed. RESULTS: Among 29 patients who underwent intra-operative oocyte retrieval during staging surgery, oocytes were obtained in 24 patients, representing 82.8 % of the retrieval rate (24/29), and two patients returned to use cryopreserved oocytes (6.9 %). Among 24 women who succeeded in obtaining oocytes, 20 patients succeeded in oocyte cryopreservation, and two patients proceeded to embryo cryopreservation. The cryopreservation rate was 91.7 % (22/24). All patients with failed oocyte retrieval (n = 5) and cryopreservation (n = 7) were diagnosed with malignancy. AMH of those with successful cryopreservation oocytes was higher than those without cryopreservation (4.10 ng/mL vs. 1.18 ng/mL, p = 0.003). A higher portion of the unstimulated cycle was observed in those with failed cryopreservation (8.3 % vs. 40.0 %, p = 0.01). No complications were noted. CONCLUSION: For women planning to undergo open pelvic surgery, intra-operative oocyte retrieval is a feasible option. High serum AMH and ovarian stimulation before surgery may predict successful oocyte cryopreservation.

Screening of cytokine expression in human seminal plasma in associations with sperm disorders and markers of oxidative-antioxidant balance.

Among the many factors with a proven relation to semen quality and male fertility, the determination of seminal plasma cytokines provides a promising direction for research into the identification of factors connected with male infertility. The interleukins: IL-1α, -1ß, -2, -4, -6, -8, -10, -12p40, -12p70, -18, IFNγ, and GM-CSF, total oxidant (TOS) and antioxidant (TAS) status, were simultaneously examined in seminal plasmas and blood sera in terato- (n = 32), asthenoterato- (n = 33), and oligoasthenoteratozoospermic (n = 29) infertile men and in normozoospermic fertile men (n = 20). Our research shows different cytokine composition of the sera and seminal plasmas in all studied groups, along with much higher concentrations of seminal plasma GM-CSF, IFNγ, IL-1α, IL-4, IL-6, and IL-8 and lower IL-18 and TOS in the comparison to their sera levels. The seminal plasma concentrations of GM-CSF, IFNγ, IL-1α, -4, and -6 differ significantly between fertile and infertile as well as between teratozoospermic, asthenoteratozoospermic, and oligoasthenoteratozoospermic groups. The indication of the cause of different concentrations of cytokines in seminal plasmas of infertile men, and their associations with semen parameters and oxidative status, may be a promising direction for the search for new therapeutic targets that would directly affect the cells and tissues of male reproductive organs.

The safety of recombinant human hyaluronidase PH20 in nonclinical models: An overview of toxicology, pharmacology, and impact of anti-PH20 antibodies.

Hyaluronan (HA) is a glycosaminoglycan that forms a gel-like barrier in the subcutaneous (SC) space, limiting bulk fluid flow and the dispersion of SC-administered therapeutics. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the rapid delivery of co-administered therapeutics by depolymerizing HA in the SC space. Administration of rHuPH20 can induce the formation of anti-rHuPH20 antibodies, or anti-drug antibodies (ADAs), with the potential to bind endogenous PH20 hyaluronidase in the adult testes and epididymis. Using a variety of relevant animal models and multiple dose regimens of rHuPH20 across the full spectrum of animal development, we demonstrated that rHuPH20 administration resulted in the formation of ADAs. Although these ADAs can bind both the recombinant rHuPH20 enzyme and recombinant versions of animal model-specific hyaluronidases, they had no impact on fertility parameters (as measured by sperm concentration and motility, litter size, and litter viability) or fetal development. We present the result of our nonclinical studies in order of the developmental lifecycle, beginning with adults. Toxicology studies that extend beyond the standard package are also presented. These studies demonstrate the favorable safety profile of rHuPH20 and ADAs in nonclinical models. Additionally, we identified substantial safety margins for therapeutically relevant doses of rHuPH20.

[Gender medicine in peritoneal diseases]. / Gendermedizin bei peritonealen Erkrankungen.

Diseases of the peritoneum are divided into benign and malignant, whereby malignant diseases are more frequent. The incidence of peritoneal metastases is difficult to determine as they are frequently not listed separately in cancer databases and registries. Peritoneal metastases can be caused by many primary tumors but are particularly frequent in gastric, ovarian and colorectal carcinomas. Systemic chemotherapy shows gender-specific differences in the tolerability, especially gastrointestinal side effects and hematological toxicity occur more often in women. Surgical treatment options in selected patients include cytoreductive surgery with or without hyperthermic intraperitoneal chemoperfusion (HIPEC). The treatment recommendations depend on the primary tumor entity and the stage of the disease. Hysterectomy and/or salpingo-oophorectomy is often necessary during cytoreductive surgery. As the incidence of cancerous diseases is increasing in younger patients, the aspect of fertility is becoming increasingly more important. The iatrogenically induced menopause is another aspect that needs to be addressed after these types of procedures. Women with gastric and colorectal cancer tend to have a slightly better survival rate, especially in localized tumors; however, in advanced tumor stages the survival rates are comparable. Even if gender-specific differences in incidence, treatment response and adverse events are conspicuous, there is so far no exact explanation for these differences. More studies are needed in order to treat both genders as adequately as possible, with low adverse events and to achieve the best possible outcome.

Comprehensive fertility preservation can be offered in a timely manner around gonadotoxic therapy in children and adolescents.

BACKGROUND: Treatment for certain childhood cancers and nonmalignant conditions can lead to future infertility and gonadal failure. The risk of treatment delay must be considered when offering fertility preservation (FP) options. We examined the timeline from FP referral to return to treatment (RTT) in pediatric patients who underwent FP due to iatrogenic risk for infertility. METHODS: A retrospective review was performed of patients with FP consultation due to an increased risk of iatrogenic infertility at Ann & Robert H. Lurie Children's Hospital of Chicago from 2018 to 2022. Data on diagnosis, age, treatment characteristics, and procedure were collected. RESULTS: A total of 337 patients (n = 149 with ovaries, n = 188 with testes) had an FP consultation. Of patients with ovaries, 106 (71.1%) underwent ovarian tissue cryopreservation (OTC), 10 (6.7%) completed ovarian stimulation/egg retrieval (OSER), and 33 (22.1%) declined FP. Of the patients with testes, 98 (52.1%) underwent testicular tissue cryopreservation (TTC), 48 (25.5%) completed sperm banking (SB), and 42 (22.3%) declined FP. Median time from referral to FP consultation was short (ovaries: 2 days, range: 0-6; testes: 1 day, range: 0-5). OSER had a significantly longer RTT versus OTC and no FP (52.5 vs.19.5 vs. 12 days, p = .01). SB had a significantly quicker RTT compared to TTC or no FP (9.0 vs. 21.0 vs. 13.5 days; p = .008). For patients who underwent OTC/TTC and those who declined FP, there was no significant difference in time from consultation to treatment. CONCLUSIONS: It is feasible to promptly offer and complete FP with minimal delay to disease-directed treatment.

Pregnancy after advanced ovarian cancer with spontaneous uterine rupture in second trimester: A case report and review of the literature.

Fertility-preserving surgery (FPS) in advanced ovarian cancer (AOC) is extremely rare and consequently, information about the pregnancies of these patients is anecdotal. Therefore, management of the pregnancy after AOC is challenging, especially if an unexpected situation arises. A 31-year-old nulliparous woman was admitted to our tertiary hospital in the 18th week of twin pregnancy with sudden severe abdominal pain. Her medical history included a low-grade AOC stage IIIc diagnosed 2 years before pregnancy and treated by debulking FPS and systemic therapy with carboplatin/paclitaxel and bevacizumab. Clinical examination described normal vital signs and peritoneal irritation without any vaginal discharge. Sonography revealed free fluid in the pouch of Douglas and intact twin pregnancy. Laboratory work showed elevated leukocytes with neutrophilia. To evaluate appendicitis magnetic resonance imaging of the abdomen was indicated. This revealed a uterine rupture with the now extra-cavitary position of the twins. Simultaneously, the patient's symptoms deteriorated, and emergency surgery was necessary where hemoperitoneum with avital fetuses were present. Despite excessive blood loss the uterus could be repaired and preserved. Previous resection of the uterine serosa during her debulking FPS, administration of bevacizumab affecting smooth muscles, and overstretching the uterus in the twin pregnancy were considered as possible risk factors for the presenting uterine rupture. Pregnancy after AOC is possible but should be monitored closely, especially due to the hidden long-term consequences of its therapy. In the differential diagnosis of sudden abdominal pain during pregnancy uterine rupture should be considered even in patients with an unscared uterus.

A new look at the theoretical causes of endometriosis: Narrative review.

Endometriosis is a major health concern in women who have it. Unfortunately, there is no definitive cure except panhysterectomy with its sequelae including induction of premature menopause due to loss of ovaries. Therefore, revealing the causes of this puzzling disease is necessary to avoid contracting it, and to spare women the health disorders resulting from it and the difficulties of treating it. We aimed to study endometriosis with a focus on its theoretical causes. Its classification reports and theories of pathogenesis were identified and studied from available database searches. The causes of endometriosis remain mysterious. Many theories have been proposed to explain the etiology, but retrograde menstruation (RM) remains the closest in this regard. Although this theory is the most accepted in the pathogenesis of endometriosis, its causes are still a matter of debate, especially in women who do not suffer from obstructions to menstrual outflows, such as cases of congenital cervical stenosis and imperforate hymen. It is suggested in some studies that there may be a relationship between women who engage in sexual activity during menstruation and the development of endometriosis. It is concluded that endometriosis is a painful and debilitating disease. Identifying its causes is essential to control the disease and avoid any burdens on health. RM is the main theory for its pathogenesis but its causes are still uncertain. Sexual activity during menstruation may be a possible cause of RM but needs more evidence. Future studies are recommended to reveal all aspects of the pathogenesis of endometriosis.

Semen Washing and Intrauterine Insemination for Reducing the Risk of Human Immunodeficiency Virus Transmission in Serodiscordant Couples: A Cross-sectional Study.

Background: Antiretroviral therapy has helped human immunodeficiency virus (HIV)-infected people live an enhanced quality of life and attempt for a pregnancy, without placing their partner at risk. Although periconceptional pre-exposure prophylaxis for the uninfected partner and consistent antiretroviral therapy for the HIV-infected partner are important to prevent HIV transmission, semen washing could be a great option to further reduce the semen viral load. Aim: The aim of this study were as follows: to determine if semen washing with intrauterine insemination provides an added safety net to HIV-serodiscordant couples when the male partner is HIV-infected and virally suppressed and to determine if the U = U concept (undetectable = untransmittable) holds true in virally suppressed HIV-infected males. Settings and Design: This was an observational study conducted in seropositive HIV men under treatment with highly active antiretroviral therapy (HAART) in collaboration with Metropolis Laboratory, a CAP recognised private Healthcare Laboratory in Mumbai, India. Materials and Methods: Blood and semen samples were collected from a total of 110 adult HIV-1-infected males virally suppressed on HAART. These samples were processed to assess the viral load in plasma as well as raw and processed semen fractions. Statistical Analysis Used: Descriptive statistics were used to analyse the data. Results: Only men with plasma viral loads < 1000 copies were selected in our study. Out of the 110 HIV-infected individuals, 102 (92.73%) patients had undetectable (<20 copies/ml) plasma viral load while 8 (7.27%) patients had a detectable (>20 copies/ml) viral load, who were excluded from the study. In the virally suppressed 102 men, the raw semen samples of 100 men showed an undetectable viral load, while 2 samples showed detectable contamination, even though their plasma samples from the blood showed a viral load of <20 copies/ml. The semen was then separated into the sperm and the seminal plasma samples. The seminal plasma had <20 copies/ml in 95 samples (93.14%) but a detectable viral load in 7 (6.86%) samples. After subjecting all the 102 processed (post-wash) sperm samples to quantitative analysis, an undetectable viral load of <20 copies/ml was found in all the samples. Thus, the raw sample (prewashed),seminal plasma and processed (postwash) samples were evaluated. The post-wash sperm sample showing zero contamination was frozen for intrauterine insemination (IUI) in the uninfected female partner. Conclusions: Semen washing with IUI should be advocated as a safe, efficacious way to increase the safety net and to further reduce the minimal risk of HIV transmission in serodiscordant couples in addition to the U = U concept.

Prostate radiotherapy may cause fertility issues: a retrospective analysis of testicular dose following modern radiotherapy techniques.

BACKGROUND: Prostate cancer in younger men is rare but not exceptional. Radiotherapy is a cornerstone of prostate cancer treatment and yet, its impact on fertility is scarcely reported in literature. Given the radiosensitivity of testicular tissue, this study aimed to determine the testicular dose using modern radiotherapy techniques for definitive prostate irradiation. METHODS: One hundred radiotherapy plans were reviewed. Testicles were contoured retrospectively without dosimetric optimization on testicles. RESULTS: The median testicular dose was 0.58 Gy: 0.18 Gy in stereotactic plans, 0.62 Gy in Volumetric Modulated Arc Therapy plans and 1.50 Gy in Tomotherapy plans (p < 0.001). Pelvic nodal irradiation increased the median testicular dose to 1.18 Gy versus 0.26 Gy without nodal irradiation (p < 0.001). Weight and BMI were inversely associated with testicular dose (p < 0.005). 65% of patients reached the theoretical dose threshold for transient azoospermia, and 10% received more than 2 Gy, likely causing definitive azoospermia. CONCLUSION: Despite being probably lower than doses from older techniques, the testicular dose delivered with modern prostate radiotherapy is not negligible and is often underestimated because the contribution of daily repositioning imaging is not taken into account and most Treatment Planning Systems underestimate the out of field dose. Radiation oncologists should consider the impact on fertility and gonadal endocrine function, counseling men on sperm preservation if they wish to maintain fertility. TRIAL REGISTRATION: retrospectively registered.

No guarantees: planned oocyte cryopreservation, not quite an insurance policy.

Planned oocyte cryopreservation (OC) has the potential to address the burden of the biological clock, giving women and individuals with ovaries more autonomy in choosing when to have children and with whom. In the United States, the annual number of OC cycles has grown significantly, yet many questions remain regarding planned OC. The field is starting to gather data on the clinical practice and social perspectives around planned oocyte cryopreservation, including the optimal age range at which to offer planned OC, what factors are most predictive of a successful outcome, and the optimal number of oocytes and ovarian stimulation cycles to achieve a live birth. There is a clear need for setting realistic expectations about the chance of success with OC; however, most patients have yet to return to thaw their oocytes, and outcomes data are limited. Clinical models have been developed to predict OC success based on surrogate markers such as age, number of oocytes retrieved, and anti-Müllerian hormone level. Patient education should emphasize the age-related decline in fertility, that eggs do not equal embryos, and that more than one cycle may be needed to obtain sufficient oocytes to have a reasonable chance of future success. While planned OC is not quite an insurance policy against future reproductive challenges, it provides the best option to date for expanding the reproductive window and maximizing reproductive options while navigating individual life circumstances in the context of family building.

Activated dormant stem cells recover spermatogenesis in chemoradiotherapy-induced infertility.

Male infertility is a recognized side effect of chemoradiotherapy. Extant spermatogonial stem cells (SSCs) may act as originators for any subsequent recovery. However, which type of SSCs, the mechanism by which they survive and resist toxicity, and how they act to restart spermatogenesis remain largely unknown. Here, we identify a small population of Set domain-containing protein 4 (Setd4)-expressing SSCs that occur in a relatively dormant state in the mouse seminiferous tubule. Extant beyond high-dose chemoradiotherapy, these cells then activate to recover spermatogenesis. Recovery fails when Setd4+ SSCs are deleted. Confirmed to be of fetal origin, these Setd4+ SSCs are shown to facilitate early testicular development and also contribute to steady-state spermatogenesis in adulthood. Upon activation, chromatin remodeling increases their genome-wide accessibility, enabling Notch1 and Aurora activation with corresponding silencing of p21 and p53. Here, Setd4+ SSCs are presented as the originators of both testicular development and spermatogenesis recovery in chemoradiotherapy-induced infertility.

Study on the value of MRI in locating the internal OS of the cervix and influencing factors.

The position of the internal os of the cervix reported in the literature was inconsistent on MRI images. Additionally, the practical impactful data influencing the internal os located by MRI is limited. We aimed to confirm the position of the internal os of the cervix on MRI images, and the influencing factors locating the the internal os by MRI. A single-center retrospective study was conducted. Data from 175 patients who underwent total hysterectomy for stage I endometrial cancer were collected. The internal os of the cervix is positioned as the starting point for measuring the length of the cervix on MRI images. On dynamic contrast-enhanced MRI (DCE-MRI), the section formed by the enhancement difference between the uterus and cervix, and on T2-weighted imaging(T2WI), the section formed by the physiological curvature of the uterus and the low signal intensity of the cervical stroma were used as starting points. The results showed no statistically significant difference compared with the removed uterus specimens (p = 0.208, p = 0.571, p = 0.804). A history of cesarean section(p < 0.001), irregular vaginal bleeding for more than three months(p < 0.001), cervical adenomyosis(p = 0.043), and premenopause(p = 0.001) were not conducive to locating the internal os of the cervix by MRI. Our findings provide valuable information and confirm the position of the internal os of the cervix on MRI images, and the several important infuencing factors. We hope that some patients will benefit from our study.

Iodine and other factors associated with fertility outcome following oil-soluble contrast medium hysterosalpingography: a prospective cohort study.

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM). Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG. Setting: Auckland, New Zealand (2019-2021). Sample: 196 women with primary or secondary infertility who underwent OSCM HSG. Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented. Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]. Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.

Uterine Transposition.

In this video, we review the steps of uterine transposition, emphasizing robotic trocar placement and docking, how to optimize organ manipulation and tissue handling, and our pearls for successful perioperative management. The patient is a 27-year-old woman with T2 node-positive rectal cancer. Uterine transposition is a new surgical procedure with limited information regarding outcomes. Although evolving over time, we present our preferred patient selection criteria and identify key stakeholders, which include colorectal surgeons, radiation oncologists, fertility specialists, social workers, and radiologists.

Addressing the consequences of the corporatization of reproductive medicine.

In Australia and the UK, commercialization and corporatization of assisted reproductive technologies have created a marketplace of clinics, products, and services. While this has arguably increased choice for patients, 'choice', shaped by commercial imperatives may not mean better-quality care. At present, regulation of clinics (including clinic-corporations) and clinicians focuses on the doctor-patient dyad and the clinic-consumer dyad. Scant attention has been paid to the conflicts between the clinic-corporation's duty to its shareholders and investors, the medical profession's duty to the corporations within which they practice, and the obligations of both clinicians and corporations to patients and to health systems. Frameworks of regulation based in corporate governance and business ethics, such as stakeholder models and 'corporate social responsibility', have well-recognized limits and may not translate well into healthcare settings. This means that existing governance frameworks may not meet the needs of patients or health systems. We argue for the development of novel regulatory approaches that more explicitly characterize the obligations that both corporations and clinicians in corporate environments have to patients and to society, and that promote fulfilment of these obligations. We consider mechanisms for application in the multi-jurisdictional setting of Australia, and the single jurisdictional settings of the UK.

Exposome Profiling of Environmental Pollutants in Seminal Plasma and Novel Associations with Semen Parameters.

Indicators of male fertility are in decline globally, but the underlying causes, including the role of environmental exposures, are unclear. This study aimed to examine organic chemical pollutants in seminal plasma, including both known priority environmental chemicals and less studied chemicals, to identify uncharacterized male reproductive environmental toxicants. Semen samples were collected from 100 individuals and assessed for sperm concentration, percent motility, and total motile sperm. Targeted and nontargeted organic pollutant exposures were measured from seminal plasma using gas chromatography, which showed widespread detection of organic pollutants in seminal plasma across all exposure classes. We used principal component pursuit (PCP) on our targeted panel and derived one component (driven by etriadizole) associated with total motile sperm (p < 0.001) and concentration (p = 0.03). This was confirmed by the exposome-wide association models using individual chemicals, where etriadizole was negatively associated with total motile sperm (FDR q = 0.01) and concentration (q = 0.07). Using PCP on 814 nontargeted spectral peaks identified a component that was associated with total motile sperm (p = 0.001). Bayesian kernel machine regression identified one principal driver of this association, which was analytically confirmed to be N-nitrosodiethylamine. These findings are promising and consistent with experimental evidence showing that etridiazole and N-nitrosodiethylamine may be reproductive toxicants.

A case report and literature review: A 19-year-old with endometrial carcinoma treated with medroxyprogesterone acetate. Importance of the medical interview and endometrial examination.

A 19-year-old woman had stage IA endometrial carcinoma treated with medroxyprogesterone acetate and experienced a recurrence. This patient's experience illustrates the importance of a thorough history and endometrial assessment in younger patients.

Clinical and pathological characteristics of cervical clear cell carcinoma in patients not exposed to diethylstilbestrol: a comprehensive analysis of 49 cases.

Purpose: This study aimed to investigate the clinical and pathological characteristics, treatment strategies, and prognosis of cervical clear cell carcinoma (CCCC) in patients not exposed to diethylstilbestrol in utero. Methods: The patients diagnosed with CCCC at West China Second University Hospital of Sichuan University between January 2011 and Jun 2023 were enrolled for this retrospective study. The clinical characteristics and information on treatment and follow-up were collected. The Kaplan-Meier method and Cox regression analysis were performed to identify the relative variables for predicting progression-free survival (PFS) and overall survival (OS). Results: Of the 49 patients included, the Federation International of Gynecology and Obstetrics (FIGO) (2018) stage distribution was 37 (75.5%) stage I, 6 (12.2%) stage II, and 6 (12.2%) stage III. The median follow-up interval was 24.1 months. Six (12.2%) patients had a recurrence, and five (10.2%) patients died. The 5-year PFS rate was 86.8%, and the 5-year OS rate was 88.2%. No recurrence or death was detected in two patients who successfully completed fertility-preserving treatment and seven patients who underwent surgery to preserve ovaries. Two patients became pregnant, giving birth to two babies. The univariate analysis showed that FIGO stage, Pelvic lymph node (PLN) metastasis, lymph vascular space invasion, and depth of stromal invasion (P < 0.05) were significantly associated with PFS and OS. However, no significant prognostic factors were identified in the multivariate analysis. Conclusion: Ovary-preserving treatment and fertility-preserving surgery are safe and feasible in early-stage CCCC. Surveillance other than adjuvant treatment may be a better choice for early-stage CCCC without any pathological risk factors. More targeted therapies and immunotherapy should be pursued in future studies.

Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.