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,thefindings 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 thisfield that upcoming research should focus on.

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.

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.

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.

Analysis of the Application Effect and Value of Dydrogesterone in The Treatment of Preeclampsia for Fetal Preservation

Objective: To analyze the application effect and value of dydrogesterone in the fertility preservation treatment of preeclampsia. Methods: Forty cases of patients with preeclampsia admitted to our hospital between January 2023 and January 2024 were divided randomly into a control group and an observation group of 20 cases each. The control group applied progesterone to preserve the fetus, and the observation group applied dydrogesterone. The symptom relief time, hormone levels before and after treatment, as well as adverse drug reactions, and the effect of fetal preservation between the two groups were compared. Results: The time to relieve vaginal bleeding, abdominal pain. and lumbago in the observation group was shorter than that in the control group (P < 0.05). After treatment, the progesterone levels and incidence of adverse drug reactions in the observation group were lower than those in the control group (P < 0.05). The success rate of fertility preservation in the observation group was higher than that in the control group (P < 0.05). Conclusion: In the treatment of fetal preservation of preeclampsia, the application of dydrogesterone positively alleviated vaginal bleeding, abdominal pain, and lumbago, with mild adverse reactions and a good effect on fetal preservation.

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.

Gonadal damage and options for fertility preservation in female and male cancer survivors

It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization （IVF） after cancer treatment are also presented.

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.

Impact of pelvic radiotherapy on the female genital tract and fertility preservation measures

Radiotherapy to the pelvis can have a major and deleterious impact on the female genital tract. Despite significant advances in the technical delivery of radical pelvic radiotherapy there remains no way to avoid delivering substantial radiation doses to the ovaries and uterus for patients undergoing treatment for gynaecological cancers. Due to improved cure rates from radical chemo-radiotherapy and social trends toward delayed childbirth many women treated for cervical cancer with radical chemo-radiotherapy will wish to attempt to preserve their fertility. Whilst there are now established and emerging techniques for preserving ovarian function and ovarian tissue, there remains the difficulty of the irradiated uterus which, even if pregnancy can be achieved, results in an increased risk for pregnancyrelated complications. Future developments may offer women in this difficult situation more and improved options for fertility preservation.

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.

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.

Fertility preservation in female cancer patients

Cancer is not rare in younger women of reproductive age therefore the preservation of fertility among them has become a significant concern due to aggressive cancer therapy they must undergo.Today different strategies for fertility preservation are available in patients at risk.However,many of these available techniques are still experimental and have limited clinical experience.Under ethical principle,better interdisciplinary cooperation between clinicians and patients,appropriate counseling and further research on cryopreservation and transplantation techniques may enhance their success to preserve fertility of young cancer victims.In this article,the existing and emerging fertility preserving strategies in young cancer female as well as their safety and ethical issues are discussed.

Successful pregnancy in a seminoma patient after fertility preservation

The frequency of invasive cancer in young patients is increasing worldwide. For patients about to undergo a surgical procedure or to receive chemical therapy, radiation therapy, loss or impairment of fertility is a major issue. So the need for fertility protection and preservation became more intensity. Sperm banking is a standard accepted procedure for males to circumvent loss or damage to spermatozoa. Here we present a successful pregnancy in a testicular germ cell tumor patient following fertility preservation.

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.

Can we grow sperm？ A translational perspective on the current animal and human spermatogenesis models

There have been tremendous advances in both the diagnosis and treatment of male factor infertility; however, the mechanisms responsible to recreate spermatogenesis outside of the testicular environment continue to elude andrologists. Having the ability to ＇grow＇ human sperm would be a tremendous advance in reproductive biology with multiple possible clinical applications, such as a treatment option for men with testicular failure and azoospermia of multiple etiologies. To understand the complexities of human spermatogenesis in a research environment, model systems have been designed with the intent to replicate the testicular microenvironment. Currently, there are both in vivoand in vitro model systems. In vivo model systems involve the transplantation of either spermatogonial stem cells or testicular xenographs. In vitro model systems involve the use of pluripotent stem cells and complex coculturing and/or three-dimensional culturing techniques. This review discusses the basic methodologies, possible clinical applications, benefits and limitations of each model system. Although these model systems have greatly improved our understanding of human spermatogenesis, we unfortunately have not been successful in demonstrating complete human spermatogenesis outside of the testicle.

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.

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.

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.

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.

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.