Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.
Pregnancy ; Female ; Humans ; Adult ; Hyperplasia ; Progestins ; Fertility Preservation ; Endometrial Neoplasms/pathology* ; Endometrial Hyperplasia/surgery* ; Treatment Outcome ; Precancerous Conditions ; Fertility ; Class I Phosphatidylinositol 3-Kinases ; Retrospective Studies

Objective: To analyze the clinical efficacy of fertility-preserving therapy in patients with atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC). Methods: The general condition, pathological type, treatment plan, tumor outcomes and pregnancy outcomes of 110 patients with AEH and EC treated with fertility-preserving therapy in Peking University People's Hospital from December 2005 to September 2019 were retrospectively analyzed. Kaplan-Meier and Log rank tests were used for survival analysis. Results: The response rate of 110 cases of AEH (62 cases) and EC (48 cases) was 94.5% (104/110) after fertility-preserving therapy. There were 93 cases (84.5%) achieved complete response and 11 cases (10.0%) achieved partial response, and the recurrence rate was 29.0% (27/93). The complete response rates of AEH and EC were 90.3% (56/62) and 77.1% (37/48), respectively, without significant difference (P=0.057). The recurrence rates of EC were significantly higher than that of AEH (40.5% vs 21.4%; P=0.022). Forty-one patients with complete response had pregnancy intention, the pregnancy rate was 70.7% (29/41), and the live birth rate was 56.1% (23/41). The live birth rate of AEH was 68.2% (15/22) and that of EC was 42.1% (8/19), the difference was statistically significant (P=0.032). The pathological type was related with the recurrence (P=0.044). Conclusions: Patients with AEH and EC can obtain high complete response rate and pregnancy rate after fertility-preserving therapy. The recurrence rate of EC is higher than that of AEH, while the live birth rate of AEH is higher than that of EC.
Endometrial Hyperplasia/surgery* ; Endometrial Neoplasms/surgery* ; Female ; Fertility ; Fertility Preservation ; Humans ; Pregnancy ; Retrospective Studies

OBJECTIVE: To analyze the efficacy and prognosis of fertility-sparing therapy of the patient with complex atypical hyperplasia (CAH) and endometrial cancer (EC). METHODS: Clinical data of 191 EC and CAH patients who received fertility-sparing therapy in Peking University People's Hospital between January 2009 and September 2021 were recruited retrospectively. Outcomes of remission, recurrence and pregnancy were analyzed. RESULTS: (1) Efficacy and efficacy-related factors: The complete response (CR) rate was 86.1% (161/187) for all the patients, and the CR rate of the CAH patients were higher than that of the EC patients (92.7% vs. 79.1%, P=0.007), the CR rate was significant higher in the CAH patients (OR=2.786, P=0.035). (2) The recurrence rate was 19.3% (31/161), and the recurrence rate of the EC patients were much higher than that of the CAH patients (26.4% vs. 13.5%, P=0.039). The median recurrence time was 22.5 (9.0, 50.0) months. (3) The high risk factors of recurrence were pathological type of EC (χ²=4.880, P=0.027), without the use of metfor-min (χ²=7.075, P=0.008), longer time to complete remission (>7 months) (χ²=6.204, P=0.013), and no pregnancy (χ²=6.765, P=0.009). (4) Results of pregnancy and related factors: Among the patients who achieved CR, 108 patients had fertility willing with the pregnancy rate of 41.7% (45/108), and the live birth rate was 34.3% (37/108). The live birth rate was lower in EC than that in the CAH patients (28.6% vs. 42.4%, P=0.045). The median time to achieve pregnancy was 10.50 (5.75, 33.25) months. The pregnancy rate was significant higher in the patients with pregnancy history (OR=9.468, P < 0.001) and in those who received assisted reproductive therapy (OR=7.809, P < 0.001). CONCLUSION Fertility-sparing therapy of CAH and EC patients is effective resulting in high disease remission and certain pregnancy. However, the high recurrence rate and low pregnancy rate are still key problems for EC and CAH patients, therefore close monitoring and follow-up are indicated.
Endometrial Hyperplasia/pathology* ; Endometrial Neoplasms/drug therapy* ; Female ; Fertility Preservation/methods* ; Humans ; Hyperplasia ; Retrospective Studies ; Treatment Outcome

Under the background of the trend in late marriage and the relaxation of family planning policy, the reproductive behavior of women has changed and the proportion of elderly pregnant women has increased progressively year by year. Thus the female fertility preservation is particularly important. As the cradle of life, uterine malformation and uterine cavity diseases may have adverse effects on embryo implantation and development. Several common intrauterine diseases, such as uterine submucosal fibroids, endometrial polyps, intrauterine adhesions, uterine malformation, cesarean scar diverticulum, and embryo residues, may affect female fertility. Hysteroscopy is the gold standard for the diagnosis and treatment for intrauterine diseases. With the progress in science and technology, the refinement of hysteroscopy instruments and the promotion of transvaginal endoscopic technology, hysteroscopy will yield brilliant results in female fertility preservation. The knowledge and training related to hysteroscopy should be continuously promoted and popularized, so that it can be mastered by more clinicians and applied in clinical practice to benefit more female patients.
Pregnancy ; Female ; Humans ; Aged ; Fertility Preservation

Background: Treatments for cancer have negative impact on fertility. Presently, there are technologies available to preserve the fertility of cancer patients even before gonadotoxic treatment is given. Several clinical practice guidelines on fertility preservation interventions for cancer patients have already been released. Among developed countries, Oncofertility is already an established field of clinical practice. Objectives: This study aims to determine the knowledge, attitudes, and practices of Filipino clinical practitioners on fertility preservation in cancer patients. Methodology: This was a cross-sectional study carried out between June and September 2019 using a self- administered questionnaire. The questionnaires were sent to clinicians (medical oncologists, hematologists, surgical oncologists, and radiation oncologists) who were directly involved in the treatment patients with cancer. Results: There were 213 respondents composed of 91 surgical oncologists (varied subspecialties), 81 medical oncologists, and 41 radiation oncologists. Most of the clinical practitioners, 58-85%, have not encountered patients who have availed of any fertility preservation method. In terms of knowledge, 53-73% of respondents were aware about some fertility preservation options, but had minimal knowledge. Ninety five percent of study participants acknowledged the need for more information on fertility preservation. Majority of clinicians (57%) have never referred to a fertility specialist; and only 38% have referred a patient for fertility preservation. The following factors were cited as barriers to discussion of fertility preservation: lack of knowledge of clinicians, poor success rates of fertility preservation, poor prognosis of patients, and prohibitive costs of treatment. Conclusion There is an acute need to increase knowledge and awareness about fertility preservation methods and international fertility preservation guidelines among Filipino health practitioners treating cancer patients.
Fertility Preservation ; Comprehensive Health Care ; Neoplasms

Background: The increasing number of young survivors after cancer treatment and of patients with non-malignant conditions who are at risk for subfertility has resulted in a demand for fertility preservation services, including the Philippines. Objective: The aim of this paper is to provide an overview of the history, indications, and management principles of fertility preservation. Also, the available strategies in the Philippines in both pre-pubertal and post-pubertal men and women and future directions of the field in the country will be discussed. Materials and methods: Literature review, historical accounts Results and conclusions Fertility preservation should be a priority when treating children and adults of reproductive age with agents that have deleterious effects on the gonads. If harmful treatment will be used, the options of fertility preservation should be discussed, as early as possible by the primary physician in collaboration with the oncologist and the reproductive medicine specialist. Most of the known options for fertility preservation are available in the Philippines and are being implemented in the local IVF centers. Recent developments hint of a potentially faster progress in the field with the establishment of the Philippine Society for Fertility Preservation in collaboration with other professional societies and a linkage with the Department of Health with the signing into law of the National Integrated Cancer Control Act of 2019.
Fertility Preservation ; Cryopreservation ; Oocytes ; Ovary ; Fertility

OBJECTIVE: To evaluate the efficacy of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment and to compare the diagnostic accuracy of endometrial aspiration biopsy with dilatation & curettage (D&C) in young women with early-stage endometrial cancer (EC) who wished to preserve their fertility. METHODS: A prospective phase II multicenter study was conducted from January 2012 to January 2017. Patients with grade 1 endometrioid adenocarcinoma confined to the endometrium were treated with combined oral MPA (500 mg/day)/LNG-IUS. At 3 and 6 months of treatment, the histologic change of the endometrial tissue was assessed. The regression rate at 6 months treatment and the consistency of the histologic results between the aspiration biopsy and the D&C were evaluated. RESULTS: Forty-four patients were enrolled. Nine voluntarily withdrew and 35 patients completed the protocol treatment. The complete regression (CR) rate at 6 months was 37.1% (13/35). Partial response was shown in 25.7% of cases (9/35). There were no cases of progressive disease and no treatment-related complications. A comparison of the pathologic results from aspiration biopsy and D&C was carried out for 33 cases. Fifteen cases were diagnosed as “EC” by D&C. Among these, only 8 were diagnosed with EC from aspiration biopsy, yielding a diagnostic concordance of 53.3% (ĸ=0.55). CONCLUSION: Combined oral MPA/LNG-IUS treatment for EC showed 37.1% of CR rate at 6 months. Considering the short treatment periods, CR rate may be much higher if the treatment continued to 9 or 12 months. So, this treatment is still a viable treatment option for young women of early-stage EC. Endometrial aspiration biopsy with the LNG-IUS in place is less accurate than D&C for follow-up evaluation of patients undergoing this treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01594879
Biopsy, Needle ; Carcinoma, Endometrioid ; Dilatation and Curettage ; Endometrial Neoplasms ; Endometrium ; Female ; Fertility ; Fertility Preservation ; Follow-Up Studies ; Humans ; Levonorgestrel ; Medroxyprogesterone Acetate ; Prospective Studies

OBJECTIVE: To evaluate patient perceptions of preoperative reproductive counseling and to evaluate complications and pregnancy outcomes in women who had radical trachelectomy (RT) for early stage cervical cancer. METHODS: Patients who underwent RT from January 1, 2004, through July 31, 2017, and had been cancer free for more than 1 year after RT were eligible; consented patients were sent a 16-item online survey. RESULTS: Of the 58 eligible patients, 39 patients (67%) completed the questionnaire. Eighteen patients (46%) reported receiving reproductive counseling and 26 (68%) reported receiving counseling about pregnancy risks and complications prior to RT, mainly delivered by gynecologic oncologists. Twenty-nine patients (74%) reported having a complication after RT, and cervical stenosis was the most common complication, occurring in 13 patients (33%). Twenty-four patients actively attempted to conceive after RT, and 20 pregnancies were achieved in 13 patients for a pregnancy rate of 54%. Eight pregnancies were spontaneous and 12 required a fertility treatment. There were 5 spontaneous first-trimester miscarriages; 14 of the 20 pregnancies (70%) resulted in live births. The median time to conception was 13.5 months (range, 1–120). CONCLUSION: A significant proportion of women with early stage cervical cancer do not receive adequate reproductive counseling before RT, and many women undergoing RT experience complications that can negatively impact their fertility. We recommend a preoperative consultation with a reproductive endocrinologist for all patients considering RT.
Abortion, Spontaneous ; Constriction, Pathologic ; Counseling ; Female ; Fertility ; Fertility Preservation ; Fertilization ; Humans ; Live Birth ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Pregnancy ; Trachelectomy ; Uterine Cervical Neoplasms

PURPOSE: Sperm cryopreservation before cancer treatment is the most effective method to preserve the fertility of male patients. We present our 21 years experience with sperm cryopreservation for cancer patients, including an examination of semen quality, the current status of cryopreserved sperm, and the rate of sperm use for assisted reproductive technology (ART). MATERIALS AND METHODS: A total of 721 cancer patients at Fertility Center of CHA Gangnam Medical Center successfully performed sperm cryopreservation for fertility preservation from January 1996 to December 2016. Medical chart review was used to analyze patient age, marital status, cancer type, semen volume, sperm counts and motility, length of storage, and current banking status. RESULTS: The major cancers of the 721 patients were leukemia (28.4%), lymphoma (18.3%), testis cancer (10.0%). The mean age at cryopreservation was 27.0 years, and 111 patients (15.4%) performed sperm cryopreservation during or after cancer treatment. The mean sperm concentration was 66.7±66.3 ×106/mL and the mean sperm motility was 33.8%±16.3%. During median follow-up duration of 75 months (range, 1–226 months), 44 patients (6.1%) used their banked sperm at our fertility center for ART and 9 patients (1.2%) transferred their banked sperm to another center. The median duration from cryopreservation to use was 51 months (range, 1–158 months). CONCLUSIONS: Sperm cryopreservation before gonadotoxic treatment is the most reliable method to preserve the fertility of male cancer patients. Sperm cryopreservation should be offered as a standard of care for all men planning cancer therapy.
Cryopreservation ; Fertility Preservation ; Fertility ; Follow-Up Studies ; Humans ; Leukemia ; Lymphoma ; Male ; Marital Status ; Methods ; Reproductive Techniques, Assisted ; Semen ; Semen Analysis ; Semen Preservation ; Sperm Count ; Sperm Motility ; Spermatozoa ; Standard of Care ; Testicular Neoplasms

The survival rates of boys and men with cancer have increased due to advances in cancer treatments; however, maintenance of quality of life, including fertility preservation, remains a major issue. Fertile male patients who receive radiation and/or chemotherapy face temporary, long-term, or permanent gonadal damage, particularly with exposure to alkylating agents and whole-body irradiation, which sometimes induce critical germ cell damage. These cytotoxic treatments have a significant impact on a patient's ability to have their own biological offspring, which is of particular concern to cancer patients of reproductive age. Therefore, various strategies are needed in order to preserve male fertility. Sperm cryopreservation is an effective method for preserving spermatozoa. Advances have also been achieved in pre-pubertal germ cell storage and research to generate differentiated male germ cells from various types of stem cells, including embryonic stem cells, induced pluripotent stem cells, and spermatogonial stem cells. These approaches offer hope to many patients in whom germ cell loss is associated with sterility, but are still experimental and preliminary. This review examines the current understanding of the effects of chemotherapy and radiation on male fertility.
Alkylating Agents ; Cryopreservation ; Drug Therapy ; Embryonic Stem Cells ; Fertility ; Fertility Preservation ; Germ Cells ; Gonads ; Hope ; Humans ; Induced Pluripotent Stem Cells ; Infertility ; Infertility, Male ; Male ; Methods ; Quality of Life ; Radiotherapy ; Spermatogenesis ; Spermatozoa ; Stem Cells ; Survival Rate ; Whole-Body Irradiation