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.

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.

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.

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.

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.

Assessing fertility preservation strategies: A scoping review

Objective:To describe the various options available for preserving female and/or male fertility,taking into account both social and medical aspects,and to identify the effects of different natural products on male infertility extracted from plants.Methods:We reviewed the literature and included full-text publications in English provided by international biomedical databases,including Sciences Direct,Google Scholar,OVID,PubMed,and MEDLINE between 2016 and 2023.Search terms,such as fertility preservation,in vitro maturation,cryopreservation,plants for the treatment of male infertility,were taken from Medical Subject Headings(MeSH)and Boolean operators were used to improve sensitivity.Results:112 papers were identified in the initial search,of which 18 were excluded due to duplication.After reviewing titles and abstracts,70 papers were finally included.The main findings of this study are presented under three key themes:gametogenesis,fertility preservation techniques,and plant-based alternatives.Regarding gametogenesis,significant progress has been made in understanding oocyte and sperm maturation,with optimized conditions improving maturation rates and motility.For fertility preservation,techniques such as rescue in vitro maturation and cryopreservation have shown the enhanced outcomes,particularly in maintaining gamete quality.Lastly,plant-based alternatives,including extracts and essential oils,have demonstrated potential in reducing oxidative stress,improving sperm motility,and supporting oocyte development,thus providing a promising complementary approach to conventional methods.Conclusions:Fertility preservation is achieved in a variety of ways,including oocyte and embryo vitrification and sperm cryopreservation,and the use of plant-based treatment of male infertility.

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.

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.