Provision of Fertility Preservation for Young Women with Early-Stage Breast Cancer

Breast cancer is the most common cancer in women worldwide, constituting 25% of all cancer diagnoses. Even though it is only affecting 4% - 6% of women under the age of 40, it remains the most common malignancy among younger patients. Advancement in the treatment and earlier detection gives excellent 5 years of survival. However, the standard treatment that comprises surgical-chemo radiation therapy or hormonal treatment often results in an increased incidence of treatment-induced infertility. Therefore, adding fertility preservation to primary cancer treatment may offer the best opportunity for future fertility. However, despite advancements in Assisted Reproductive Technology (ART), the uptake of fertility services in this group remains low. In this review, we highlighted the effect of all breast cancer treatments on women’s fertility, the effectiveness and safety of ART in breast cancer patients as well as the safety of pregnancy in breast cancer survivors. Our aim is to improve awareness of fertility preservation for breast cancer to ensure all women diagnosed with breast cancer have multidisciplinary approaches with early referral to fertility specialists to discuss regarding potential risks and benefits of fertility preservation to improve the uptake of fertility preservation among this group of patients.

Stem cell-based therapies for fertility preservation in males:Current status and future prospects

With the decline in male fertility in recent years,strategies for male fertility preservation have received increasing attention.In this study,by reviewing current treatments and recent publications,we describe research progress in and the future directions of stem cell-based therapies for male fertility preservation,focusing on the use of spermatogonial stem cells(SSCs),SSC niches,SSC-based testicular organoids,other stem cell types such as mesenchymal stem cells,and stem cell-derived extracellular vesicles.In conclusion,a more comprehensive understanding of the germ cell microenvironment,stem cell-derived extracellular vesicles,and testicular organoids will play an important role in achieving male fertility preservation.

Update Knowledge Assessment and Influencing Predictor of Female Fertility Preservation in Oncologists

Objective:This study aims to offer an update assessment of the knowledge of Chinese oncologists on female fertility preservation,and identify the determinants that influence the implementation of fertility preservation.Methods:A total of 713 Chinese oncologists with different specialties completed the online self-report questionnaire to assess their understanding of fertility risks in cancer treatment,knowledge on female fertility preservation,and perceptions on the barriers in referring patients for fertility preservation.Results:Although most oncologists were familiar with fertility risk in cancer treatment,half of them lacked the knowledge for reproduction and preservation methods.In the multivariable model,oncologists in a hospital with a specialized reproductive institution,positive precaution for fertility risk,and fertility preservation discussion with patients were significantly correlated with the possibility of fertility preservation referral.Conclusions:The intervention targets based on the update evaluation and identified influencing determinants will be helpful for all the oncofertility researchers,oncologists and institutions in future efforts for well-established female fertility preservation services.

Conservative laparoscopic surgery of adnex torsion for fertility preservation

Objectives:To evaluate the safety and efficacy of conservative laparoscopic surgery for adnexal torsion and the feasibility of secondary operation.Methods:This is a retrospective study that consists of 17 patients with clinically diagnosed adnexal torsion who have a desire for pregnancy in the future.We performed conservative laparoscopic adnexal detorsion operations from January 2014 to June 2016 in Sir Run Run Shaw Hospital.The collected data,including age,onset time,maximum diameter of adnexal lesion,local blood flow signal,torsion degree,and recovery of local blood supply after detorsions,were analyzed.The blood flow of the lesion side,the antral follicles development,the basal endocrine hormone levels and the menstrual cycle were examined one-month and three-month post operation.Future fertility was investigated postoperatively.Results:All cases had no obvious clinical postoperative complications.There were no significant changes on menstrual cycle and ovarian function during the follow-up period.Conclusions:Adnexal torsion in young patients should be carefully treated and fertility reservation should be thoroughly considered.The decision to remove adnexa needs careful consideration.Conservative laparoscopic surgery is safe and does not increase the occurrence of serious complications.There is a higher possibility of a long delay between surgery and onset necrosis,but this is not always the case.Even if there is adnex thromboembolic infarction it does not result in serious complications such as pulmonary infarction.Conservative laparoscopic surgery can be performed first unless the clinician is certain it is already necrotic.We should do our best to reserve patients’fertility as much as possible.If necessary,a secondary surgery can be performed.

Chinese expert consensus on clinical practice of female fertility preservation

Many female fertility preservation-related technologies have recently been developed in response to increasing demand for such treatments. To establish standard practices of female fertility preservation in China, the Chinese Maternal and Child Health Association Affiliated Fertility Preservation Professional Committee assembled specialists to construct a consensus, referring to the current clinical guidelines of some countries combined with clinical practice and expert opinions. The consensus includes two parts: (1) indications for female fertility preservation and related techniques, in which we sought to be inclusive regarding the indications for fertility preservation;and (2) practical guidance for the clinical application of the female fertility preservation technologies.

Source of human oocytes for infertility treatment and fertility preservation

The source of human oocytes is directly associated with the success of infertility treatment and fertility preservation. The number of oocytes obtained is possibly correlated with the success rate in terms of live birth rates. However, oocyte quality must be refined such that the number of oocytes is not positively correlated with the quality of oocytes. Different ovarian stimulation protocols can be used to obtain numerous oocytes. However, oocyte quality should be considered the most important factor affecting infertility treatment and fertility preservation. Infertile women are generally willing to take health-related risks to achieve a live birth, and ovarian stimulation using high-dose hormonal treatments may be harmful for both women and infants. Therefore, successful infertility treatment and fertility preservation should be defined as the birth of a healthy baby at term without compromising the health and safety of the mother and infant. Therefore, the source of high-quality oocytes must be carefully considered prior to infertility treatment and fertility preservation.

Fertility Preservation in Cancer Patients

Traditional radiotherapy and chemotherapy often cause irreversible damage to the fertility and endocrine function of cancer patients.The current methods of fertility preservation include freezing the sperms of adult and adolescent males after puberty;freezing the embryos,oocytes,and ovarian tissue of females;and drug intervention and fertility preservation surgery.This article reviews fertility preservation in cancer patients with respect to current methods,indications,and some more recently developed methods that remain under investigation.

How fertility preservation guidelines have progressed worldwide:Potential implications and inspiration

To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women’s and Children’s Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.

Fertility preservation for female patients with childhood and adolescent cancer

With the significant cancer treatment in the past decades,>85%of children with cancer now survives into adulthood,and fertility preservation has become an important quality-of-life technology for them.1 Cancer treatment may include surgery,chemotherapy,radiotherapy,and/or hematopoietic stem cell transplantation(HSCT).2 Except for non-pelvic surgery,these treatments may affect ovarian function and consequently cause varying degrees of gonadal toxicity.3 Patients cured by anti-cancer treatment have a very high risk of premature ovarian insufficiency(POI).

Reproductive advance of fertility preservation in patients with early endometrial carcinoma or endometrial atypical hyperplasia

Endometrial cancer(EC)is the fourth common cancer in women worldwide with its incidence rising each year.10%–15%young patients are diagnosed of EC.For patients of childbearing age with early endometrial cancer or atypical hyperplasia,it is necessary to consider surgical removal of uterus after they have given birth.It is a big challenge for reproductive doctors and oncologists to help such patients get pregnant safely as soon as possible.In this article,we will review the latest progress in conservative treatment and candidates for fertility preservation,application of molecular detection,the fertility outcome and follow-up treatment which aims to stimulate more thinking.

Abnormal uterine bleeding successfully treated via ultrasoundguided microwave ablation of uterine myoma lesions: Three case reports

BACKGROUND Microwave endometrial ablation(MEA)is a minimally invasive treatment method for heavy menstrual bleeding.However,additional treatment is often required after recurrence of uterine myomas treated with MEA.Additionally,because this treatment ablates the endometrium,it is not indicated for patients planning to become pregnant.To overcome these issues,we devised a method for ultrasound-guided microwave ablation of uterine myoma feeder vessels.We report three patients successfully treated for heavy menstrual bleeding,secondary to uterine myoma,using our novel method.CASE SUMMARY All patients had a favorable postoperative course,were discharged within 4 h,and experienced no complications.Further,no postoperative recurrence of heavy menstrual bleeding was noted.Our method also reduced the myoma’s maximum diameter.CONCLUSION This method does not ablate the endometrium,suggesting its potential appli-cation in patients planning to become pregnant.

Oncological and Reproductive Outcomes of Fertility-sparing Surgery in Women with Early-stage Epithelial Ovarian Carcinoma:A Multicenter Retrospective Study

Summary:With delayed childbearing in women,preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma(EOC).Fertility-sparing surgery(FSS)can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life.In order to evaluate oncological safety,attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS,this multicenter retrospective study was conducted.Between January 2005 and December 2014,total of 87 young women with FIGO stage I EOC were included,with their clinicopathologic parameters in relation to disease-free survival(DFS)and overall survival(OS)assessed.Attitudes toward childbearing,ovarian function and fertility were studied in women undergoing FSS(n=36).As a result,in contrast to radical sur ery,FSS did not affect prognosis by Kaplan-Meier curves(log-rank test;DFS:P=0.484;OS:P=0.125).However,two of the three recurrence cases and both death cases were in FSS group stage IC.All women undergoing FSS resumed regular menstrual periods after chemotherapy.Only 16(44.44%)had tried to conceive,and 17 pregnancies occurred in 15(93.75%)women.Among 20 women who did not attempt conception,the most common reason was not being married(70%),followed by already having children(15%).In summary,FSS is considered safe in young women with stage IA EOC.Regular menstruation and good obstetric outcomes can be achieved.This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.

Ultrasound-guided local ethanol injection for fertility-preserving cervical pregnancy accompanied by fetal heartbeat: Two case reports

BACKGROUND The incidence of cervical pregnancy is increasing due to the recent widespread application of assisted reproductive technology.Although hysterectomy has been a treatment option,high-sensitivity human chorionic gonadotropin testing and improved accuracy of transvaginal ultrasound imaging have increased possibility of uterine preservation.Dilation and curettage with methotrexate therapy and uterine artery embolization have been reported as treatments with fertility preservation;however,certain disadvantages limit their use.CASE SUMMARY In our two reported cases,we avoided massive bleeding and immediately resumed infertility treatment using ultrasound-guided local ethanol injection for cervical pregnancies with fetal heartbeats.CONCLUSION This treatment may be a new fertility-preserving option for cervical pregnancy.

Prevention and treatment of iatrogenic premature ovarian insufficiency:r interpretation of the first Chinese guideline on ovarian tissue cryopreservation and transplantation

In recent years,with the rapid development of medical research,cancer diagnosis and treatment technology have significantly improved young cancer patient’s survival rate.Anticancer therapy such as chemotherapy,radiotherapy,or hematopoietic stem cell transplantation can lead to premature ovarian insufficiency.The endocrine and reproductive function of the ovary is critical to women’s physical and mental health.Ovarian tissue cryopreservation and transplantation can protect not only female fertility but also preserve ovarian endocrine function.This paper interprets the guidelines for ovarian tissue cryopreservation and transplantation issued by the Chinese Society of Gynecological Endocrinology affiliated to the International Society of Gynecological Endocrinology.The purpose of this guideline’s interpretation is to promote more medical workers to understand the technology of ovarian tissue cryopreservation and transplantation,which can provide patients with more choices of fertility protection methods and improve their quality of life.

Role of Ovarian Fertility Sparing Surgery (FSS) in Cases of Early Stage 1 Ovarian Cancer in Patients in Reproductive Age Group

Objective: To assess the role of FSS in women with early stage 1 ovarian cancer. Methods: This was a retrospective analytic study of the results of treatment of 24 patients all under 40 years of age who underwent a full conservative staging laparotomy procedure in oncology center of El Shatby Maternity hospital, Alexandria University in the period of one year from October 2019 to September 2020. All patients were followed up for a six month period following surgery by the pre-operatively elevated tumor marker and by a CT abdomen and pelvis to detect any tumor recurrence. Results: The mean age at diagnosis was 24.29 Years. 6/24 (25%) of surface epithelial tumor were G1, 8/24 (33.3%) were G2, 4/24 (16.7%) were G3. 20/24 (83.3%) of patients were stage FIGO 1a, 4/25 (16.7%) were stage 1b, and none of them was stage 1c. 20/24 (83.3%) of patients were stage FIGO 1a, 4/25 (16.7%) were stage 1b, and none of them was stage 1c. Recurrence was reported in 3/24 of cases (12.5%), such 3 cases underwent unilateral SO plus a FCSLP. No recurrence was reported in cases of bilateral tumors that underwent unilateral SO and a contralateral cystectomy. 100% of recurrence was in epithelial tumors. 1/24 (4.1%) was clear cell, 1/24 (4.1%) was serous and 1/24 (4.1%) was mucinous. None of the endometroid tumors did recur. Also none of the non-epithelial tumors showed any recurrence. Tumors of G1 showed no recurrence, G2 tumors showed 33.3% recurrence and G3 tumors showed the highest recurrence rate (66.6%). Conclusion: ovarian FSS is a safe surgical option for nearly all OC patients with low risk of recurrence, with apparently early stage OC, after being confirmed by a FCSLP to exclude any occult metastasis (occult advanced stage OC), including those cases of early epithelial OC, germ cell and gonadal stromal tumors and it should be considered for patients who have a strong desire to keep their fertility.

A Retrospective Study on the Use of High-Dose Letrozole while Undergoing Ovarian Stimulation for Oocyte and Embryo Cryopreservation in Cancer Patients

Objective: To determine the efficacy of letrozole in suppressing estradiol levels during ovarian stimulation in cancer patients. Methods: A retrospective chart review of cancer patients undergoing ovarian stimulation for fertility preservation between 2014-2019 at a private university-affiliated fertility clinic in Canada was conducted. Ovarian stimulation was completed with no letrozole (Group A, n = 10), and adjuvant daily letrozole use at 5.0 (Group B, n = 34) or 7.5 mg (Group C, n = 61). The primary outcomes were peak estradiol levels and oocyte yield. ANOVA with a post hoc two-tailed t-test assuming equal variance was utilized as a statistical method. Result(s): Patient age and AFC count were not different between groups. The yield of mature eggs was not different at each letrozole dose;9.2 ± 6.0, 13.9 ± 6.5 and 12.7 ± 7.2 for Groups A to C respectively (p = 0.18). Mean estradiol levels(pmol/L) were reduced in a dose-dependent manner;7432 ± 4553 for Group A, 2072 ± 1656 for Group B, and 1445 ±1238 for Group C (A vs. C, p vs. C, p Conclusion(s): The use of letrozole during ovarian stimulation for oocyte and embryo cryopreservation in cancer patients can maintain physiologic estradiol levels, while ensuring satisfactory oocyte and embryo yield. Letrozole can, therefore, minimize the theoretical risk of stimulating residual and metastatic diseases, while still optimizing future fertility outcomes.

Cesarean Scar Pregnancy: A Report of 11 Cases and Review of the Literature Regarding Subsequent Pregnancy

Background: There is no consensus regarding the optimal treatment for cesarean scar pregnancy (CSP) because treatment efficacy, safety, and the influence on subsequent pregnancy must be taken into consideration. Here we report our experience with 11 cases of CSP and review the literature regarding subsequent pregnancy. Methods: Records of 11 CSP cases that were treated at our hospital were retrospectively reviewed. CSP was treated by local methotrexate (MTX) injection or laparotomic or laparoscopic removal of the gestational mass and myometrial repair. Outcome of subsequent pregnancy after treatment was followed-up until delivery. Results: Local MTX injection was performed for six cases, laparotomic removal of the gestational mass and myometrial repair was performed for two, and laparoscopic removal of the gestational mass and myometrial repair was performed for three. The uterus was preserved in all cases. After CSP treatment, eight pregnancies occurred in five cases, resulting in six live births and two miscarriages. Conclusion: Advantages and disadvantages of various treatment methods for CSP continue to be elucidated. Serum hCG level, location of the gestational mass, thickness of the lower uterine segment at the time of diagnosis, and whether the patient wishes for fertility preservation should be considered when choosing a treatment plan.

A retrospective study on sperm cryopreservation in 1034 patients diagnosed with cancer in southern China

Sperm cryopreservation is an effective fertility preservation method for cancer patients before anticancer treatments. However, thereare little data on fertility preservation in large cohorts of patients with cancer in southern China. This retrospective cross-sectionalstudy aimed to assess the fertility preservation status of 1034 newly diagnosed male patients with cancer in the Human SpermBank of Guangdong Province in southern China (Guangzhou, China). Of these, 302 patients had reproductive system tumors,mostly testicular cancers (99.0%), and 732 had other tumors, including lymphoma (33.1%), gastrointestinal cancer (16.3%),nasopharyngeal carcinoma (15.7%), leukemia (7.7%), sarcoma (3.6%), and others (23.6%). Patients with reproductive systemtumors had lower sperm concentration and prefreezing and post-thawing progressive motility than those with non-reproductive systemtumors (all P < 0.001). Differences in sperm concentration, progressive motility, and normal morphology rate were observed betweenpatients with and without anticancer surgery before sperm cryopreservation (all P < 0.05). As of April 30, 2022, 63 patients usedtheir cryopreserved sperm for assisted reproductive technology treatments and 39 pregnancies were achieved. This study providesvaluable data on the fertility preservation status in newly diagnosed cancer patients in southern China, demonstrating that patientswith reproductive system tumors had poor sperm quality for their pretreatment fertility preservation.

Oncofertility:Treatment options from bench to bedside

In recent years,there has been continuous improvement in the treatment and diagnosis of cancer,which has led to a significant improvement in the survival rate of cancer patients.Treatments that include chemotherapy,radiotherapy,surgery,or combined therapy have several side effects that may lead to premature ovarian insufficiency in females or substantial male germ cell loss.Reproductive biologists recommend that all patients who are diagnosed with a malignant tumor must undergo a consultation for fertility protection and preservation.In this review,we discuss the background knowledge,methods,and options for fertility preservation and how these new strategies help oncologists,surgeons,pediatricians,and hematologists,conserve fertility and be aware of the concepts,methods,and importance of fertility guards.This review may aid in the advancement of novel personalized methods for fertility preservation according to patients’conditions.

Postnatal germ cell development in cryptorchid boys

Cryptorchidism is associated with infertility in adulthood.Early orchiopexy is suggested to reduce the risk.Information is lacking on the potential link between infant germ cell maturation and the risk of future infertility.The objective of the study was to evaluate age-related germ cell development in cryptorchidism.Immunostaining for markers of germ cell development(octamerbinding transcription factor 3/4[0CT3/4],placental alkaline phosphatase[PLAP],KIT proto-oncogene[C-KIT],podoplanin[D2-40],Lin-28 homolog A[LIN28],and G antigen 7[GAGE-7])was performed in testicular biopsies from 40 cryptorchid boys aged 4-35 mon ths.Germ cell nu mbers and distributi ons were evaluated in cross sectio ns of semi niferous tubules,with and without immuno staini ng.OCT3/4,D2-40,and LIN 28 were gen erally expressed in the early stages of germ cell development,as show n by positive expression in germ cells in the central region of seminiferous tubules・In contrast,PLAP and GAGE-7 were expressed in both central and peripheral parts of the tubules in the early stages of development and expressed mainly in a peripheral position with advancing age.Germ cell maturation was delayed in this study population as compared with that observed in our previous study on germ cell markers in a healthy population.The number of GAGE-7-positive germ cells per tubular cross section obtained by immunostaining was significantly higher than that obtained by standard hematoxylin and eosin staining.Double immunostaining revealed heterogeneity in germ cell development in cryptorchid testes.These results shed light on the pathophysiology of germ cell development in boys with cryptorchidism.