Fertility Preservation In Women Research Articles

Uterine transposition for gynecological cancers

ObjectiveUterine transposition has emerged as an alternative for fertility preservation in women with pelvic malignancies that require radiotherapy. The goal of this study was to evaluate the short-term outcomes of...

Fertility preservation in women with ovarian cancer: Finding new pathways: A case-control study.

Background Surgery and chemotherapy are the two most common treatments for cancers, including ovarian cancer. Although most ovarian cancers occur over the age of 45 yr, it may involve younger women and affect their reproductive ability.Objective To assess the expression of Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), Forkhead Box O1 (FOXO1), and miR-340 genes in the ovarian cancer tissues as well as ovarian cancer cell lines.Materials and Methods In this case-control study, 30 ovarian cancer samples (with the average age of 37 2.5 years) coupled with their non-tumor marginal tissue (as a control) were collected. Proliferated cell lines were treated with several concentrations of cisplatin, and the half maximal inhibitory concentration (IC50) of cisplatin was quantified by MTT-assay. After RNA extraction, cDNA synthesis and qRT-PCR were done. Finally, the results were analyzed.ResultsWhile the expression levels of miR-340 and FOXO1 genes in tumor samples displayed a significant reduction (p 0.001), the LGR5 gene presented a significant increase in expression (p 0.0001). However, conversely, the expression levels of miR-340 and FOXO1 genes in cisplatin-sensitive cell lines, after 24, 48, and 72 hr of cisplatin treatment, indicated a significant increase (p 0.001) while the expression of LGR5 gene showed a significant decrease in the cisplatin-sensitive cell line (p 0.05).ConclusionThe LGR5, FOXO1, and miR-340 genes can be targeted for early diagnosis and more accurate treatment of ovarian cancer and may prevent some of the ovarian cancer complications such as infertility.

The Perspectives of Fertility Preservation in Women with Endometrial Cancer.

Simple SummaryEndometrial cancer is a common gynecological malignant disease. Its incidence in women of reproductive age in developed countries is increasing. The standard treatment is surgical in the form of hysterectomy and bilateral salpingo-oophorectomy, which has a significant impact on the quality of women’s lives and precludes further fertility. Conservative management to preserve reproductive function and delay final surgery can today be considered in carefully selected women. We analyze the current approaches to select appropriate candidates and current medical regimens for fertility sparing management. We elaborate on the future perspectives of management. With better characterization of the disease and implementation of molecular biomarkers, more women should be able to benefit from conservative approaches to management of endometrial cancer.Endometrial cancer is the most common gynecological cancer in developed countries. The disease is diagnosed with increasing frequency in younger women, commonly also in their reproductive age. The standard treatment of endometrial cancer is surgical in the form of hysterectomy and bilateral salpingo-oophorectomy, and this precludes future fertility in younger women. The current challenge is to identify the group of women with endometrial cancer and low-risk features that would benefit from more conservative treatment options. More focus in management needs to be aimed towards the preservation of quality of life, without jeopardizing oncological outcomes. In this review, we analyze the current approaches to identification of women for conservative management and evaluate the success of different medical options for treatment and surgical techniques that are fertility sparing. We also elaborate on the future perspectives, focusing on the incorporation of molecular characterization of endometrial cancer to fertility preservation algorithms. Future studies should focus specifically on identifying reliable clinical and molecular predictive markers in this group of young women. With improved knowledge and better risk assessment, the precision medicine is the path towards improved understanding of the disease and possibly widening the group of women that could benefit from treatment methods preserving their fertility.

Number needed to freeze: cumulative live birth rate after fertility preservation in women with endometriosis

Research questionHow does the number of oocytes used affect the cumulative live birth rate (CLBR) in endometriosis patients who had their oocytes vitrified for fertility preservation? DesignRetrospective observational study including data from 485 women with endometriosis who underwent fertility preservation from January 2007 to July 2018. Survival curves and Kaplan–Meier plots were used to analyse the CLBR according to the number of vitrified oocytes used. Endometriosis curves were compared with plots developed using elective fertility preservation (EFP) patients as control group. Log-rank, Breslow and Tarone–Ware tests were used to compare the survival curves. ResultsThe CLBR increased as the number of oocytes used per patient rose, reaching 89.5% (95% confidence interval [CI] 80.0–99.1%) using 22 oocytes. Higher outcomes were observed in young women (≤35 years old versus >35 years old). In the younger group, the CLBR was 95.4% (95% CI 87.2–103.6%) using approximately 20 oocytes versus 79.6% (95% CI 58.1–101.1%) in older women (log-rank [Mantel–Cox] P = 0.002). The mean age was higher in EFP patients (37.2 ± 4.9 versus 35.7 ± 3.7; P < 0.001). The outcome was better in the endometriosis group as compared with EFP: a CLBR of 89.5% (95% CI 80.0–99.1%) versus 59.9% (95% CI 51.4–68.6%) when 22 oocytes were used (log-rank [Mantel–Cox] P < 0.00001). ConclusionThe probability of live birth increases as the number of oocytes used increases in patients with endometriosis, but better outcomes were observed among young women. The information provided here may be of interest to both patients and treating physicians for counselling purposes.

Fertility preservation in women with early ovarian cancer.

Fertility preservation is an important option to consider for young women with low-grade early ovarian cancer. Fertility-sparing surgery ("FSS") permits the conservation of the uterus and one of the ovaries. This technique is considered safe for stages IA G1, G2 and probably safe for IC G1 epithelial and non-epithelial ovarian cancers. There are still uncertainties and FSS is not fully accepted for stage IC G1, G2 and clear cell carcinoma. The difficulty in choosing the best option lies in the fact that there is a lack of prospective randomized studies, due to ethical and organizational issues. Retrospective studies and reviews showed reassuring results for FSS in terms of relapse and long term survival. The spontaneous pregnancy rate seems to decrease after FSS, but chemotherapy does not seem to have an impact on fertility rates. Compared with the general population, assisted reproductive techniques are considered safe and with similar fertility results.

Information needs and research priorities for fertility preservation in women with breast cancer: patients and experts' perspectives.

To identify the information needs and research priorities that women with breast cancer (BC), their families and BC experts perceive on the fertility preservation. We conducted two Delphi-based studies through three online rounds. The first was aimed to identify information and research needs; the second one to assess the importance of those needs and the third one to obtain consensus, defined as an interquartile range ≤2. The participation rate was 76.2% in study 1 and 53.7% in study 2. The most important information needs were the referral protocol, pregnancy options for women with BC, side effects of tamoxifen and menopause as a consequence of treatment. The most important research priorities were the participation of different health professionals to provide oncofertility information, referral protocols and efficacy and safety of FP options. Information about fertility preservation in the context of BC and different ways to get pregnant, considering risks and benefits, has emerged as an unmet need for patients and careers. The need for a participatory and coordinated approach to the provision of information on oncofertility has been agreed. Other research needs are described in an attempt to focus future research in the most necessary areas.

Evaluation of physicians’ practice patterns in France concerning fertility preservation in women with endometriosis

ObjectiveWe aim to evaluate the knowledge and physicians’ practices concerning fertility preservation in women with endometriosis. DesignDescriptive, observational, national study using an online self-questionnaire, sent by email to French gynaecologists in October 2019 within 2 months. ResultsWe obtained 110 analyzable responses from mainly surgeons (54 %) and reproductive clinicians (19 %) with a good experience (average 15 years of practice). Amongst these practitioners, 91 % seemed aware of latest French recommendations on endometriosis issued in December 2017. The most commonly used surgical techniques for management of endometriomas were intra-peritoneal cystectomy (51 %), vaporization by plasma energy (29 %) and destruction by bipolar coagulation (8.5 %). Preoperative AMH was systematically or often prescribed by 78 % of the practitioners against 37.3 % who did it postoperatively. Furthermore, 74 % also considered and performed fertility preservation strategy to manage endometriosis. It was offered in situations of bilateral or recurrent endometrioma, but only 33 % offered it in unilateral endometrioma cases. In the cases recorded, vitrification of mature oocytes appears to be the most common fertility preservation technique (used by 87 % of the practitioners). ConclusionWe observed in our population of sensitized practitioners a good and adequate knowledge concerning endometriosis physiopathology and recommendations for its management, with good information delivery to women. Operating techniques are adapted although information and education concerning fertility preservation indications seem necessary. The place of multidisciplinary concertation meeting in endometriosis appears essential both for discussion of surgical indications and for fertility preservation possibilities. Creation of dedicated structures should be encouraged.

Controlled ovarian hyperstimulation for fertility preservation in women with breast cancer: Practical issues.

In Korean women, a westernized lifestyle is associated with an increased risk of breast cancer. Fertility preservation has become an increasingly important issue for women with breast cancer, in accordance with substantial improvements in survival rate after cancer treatment. The methods of controlled ovarian hyperstimulation (COH) for fertility preservation in breast cancer patients have been modified to include aromatase inhibitors to reduce the potential harm associated with increased estradiol levels. Random-start COH and dual ovarian stimulation are feasible options to reduce the total duration of fertility preservation treatment and to efficiently collect oocytes or embryos. Using a gonadotropin-releasing hormone agonist as a trigger may improve cycle outcomes in breast cancer patients undergoing COH for fertility preservation. In young breast cancer patients with BRCA mutations, especially BRCA1 mutations, the possibility of diminished ovarian reserve may be considered, although further studies are necessary. Herein, we review the current literature on the practical issues surrounding COH for fertility preservation in women with breast cancer.

Fertility preservation in women with endometrial cancer

Fertility preservation should only be offered to patients with endometrial cancer stage Ia grade 1 (G1), who present without myometrial invasion or where the cancer has invaded less than 50% of the myometrium, with no evidence of pathological lymph nodes or no evidence of synchronous or metachronous ovarian tumor. It is estimated that about 22% will achieve successful pregnancy.

Advances in the Treatment and Prevention of Chemotherapy-Induced Ovarian Toxicity.

Due to improvements in chemotherapeutic agents, cancer treatment efficacy and cancer patient survival rates have greatly improved, but unfortunately gonadal damage remains a major complication. Gonadotoxic chemotherapy, including alkylating agents during reproductive age, can lead to iatrogenic premature ovarian insufficiency (POI), and loss of fertility. In recent years, the demand for fertility preservation has increased dramatically among female cancer patients. Currently, embryo and oocyte cryopreservation are the only established options for fertility preservation in women. However, there is growing evidence for other experimental techniques including ovarian tissue cryopreservation, oocyte in vitro maturation, artificial ovaries, stem cell technologies, and ovarian suppression. To prevent fertility loss in women with cancer, individualized fertility preservation options including established and experimental techniques that take into consideration the patient’s age, marital status, chemotherapy regimen, and the possibility of treatment delay should be provided. In addition, effective multidisciplinary oncofertility strategies that involve a highly skilled and experienced oncofertility team consisting of medical oncologists, gynecologists, reproductive biologists, surgical oncologists, patient care coordinators, and research scientists are necessary to provide cancer patients with high-quality care.

Ovarian response to stimulation for fertility preservation in women with hematologic cancer

PurposeTo compare the ovarian response to controlled ovarian hyperstimulation (COH) in patients with hematologic malignancies treated for fertility preservation (FP) and healthy subjects (oocyte donors (OD)). Patients and MethodsRetrospective cohort study comparing 41 women (18–37 years) who underwent COH for oocyte vitrification prior to gonadotoxic treatment for hematologic cancer (FP group) from January 2014 to February 2019 and with 117 women undergoing COH as part of an OD protocol (OD group) during the same period. The number of frozen mature oocytes, number of oocytes retrieved, total dose of rFSH, maximal estradiol levels, percentage of maturity, number of dominant follicles >14 mm, days of stimulation were evaluated. Results were adjusted for age, body mass index (BMI), anti-Mullerian hormone (AMH) and rFSH starting dose. ResultsPatients in the FP group were younger and had a lower BMI than those in the OD group. rFSH starting dose was higher in the FP group (median 225UI (125;450) vs 150UI (87.5;337.5), p < 0.0001). After adjusting for age, BMI and starting rFSH dose according to ANCOVA, more frozen mature oocytes (median 10 (0;45) vs 8 (0;22] p = 0.0055) and retrieved oocytes (median 12 (0;49) vs 11 (0;29) p = 0.0468) were found in the FP group. Other outcome measures did not differ between the groups. ConclusionOvarian response after COH in women with a hematologic cancer is similar to that in the general population. A higher number of mature oocytes were collected in the FP group after strong COH.

The indication for fertility preservation in women with Turner syndrome should not only be based on the ovarian reserve but also on the genotype and expected future health status.

Fertility preservation in women with Turner syndrome is highly controversial. Some strongly recommend freezing of ovarian tissue at a young age, others do not. The controversy is partly due to different perspectives and professions. Biologists prefer to freeze young ovaries with high follicle density, reproductive physicians want to avoid risky operations and iatrogenic infertility by removing one ovary, and cardiologists and obstetricians warn against the risks of later pregnancies. Accordingly, fertility preservation in young women with Turner syndrome is more than just the freezing of ovarian tissue or oocytes. Fertility preservation requires a balanced decision considering the conservation of fertility, the protection of reproductive health, and future health consequences. Therefore, fertility preservation strategies should be based not only on the individual ovarian reserve but also on the genotype and the expected cardiac health status to decide what is the best option: to freeze tissue or alternatively to wait and see.

Fertility preservation in women with cervical cancer.

Fertility preservation in women with cervical cancer is a demanding but evolving issue. Some remarkable achievements have been reached, in particular the improvement of primary and secondary prevention and the broadening of the indications for conservative surgery up to FIGO 2018 stage IB2. Natural pregnancy rate and the rate of obstetrics complications following conservative approach is satisfactory even if not optimal. On the other hand, the use of classic strategies for fertility preservation such as oocytes or ovarian cortex freezing is extremely limited, being the uterus compromised by treatment in a high proportion of cases. In fact, the availability of uterine surrogacy can play a role in the counseling and the decision-making process. The recent advent of uterus transplantation is fascinating but, at present, cannot be viewed as a realistic solution.

Fertility preservation for women undergoing breast cancer treatment: A postcode lottery?

Fertility preservation for women undergoing breast cancer treatment: A postcode lottery?

Use of fertility treatments in BRCA1/2 mutation carriers and risk for ovarian and breast cancer: a systematic review

PurposeMutations in the genes BRCA1 and BRCA2 represent a significant risk factor for ovarian and breast cancer. With increasing number and success rates, fertility protection and treatment are gaining importance also for BRCA1/2 mutation carriers. However, the effect on primary cancer risk and risk for recurrence remains unclear. This review analyses the published data on fertility treatment and risk of ovarian and breast cancer in BRCA1/2 mutation carriers.MethodsIn this review, we included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library.ResultsWe identified one retrospective cohort and one case–control study regarding the association of fertility treatments and ovarian cancer risk in BRCA mutation carriers. The studies show no increase in ovarian cancer risk. Furthermore, one case–control study on the association between fertility treatment and breast cancer risk in BRCA mutation carriers and one prospective cohort study on the long-term safety of medication used for fertility preservation in women with a history of breast cancer were identified. One of the studies shows a possible adverse effect for gonadotropin-containing medication.ConclusionPossible increases in cancer risk associated with fertility treatments in BRCA1/2 mutation carriers cannot be excluded at this time. Based on the existing studies, BRCA1/2 mutation carriers should not be generally excluded from fertility treatments. However, they have to be informed about limited data and possible increases in cancer risk.

Fertility preservation in women for medical and social reasons: Oocytes vs ovarian tissue.

Approximately 10% of cancers occur in women under 45 years of age. Chemotherapy, radiotherapy, and bone marrow transplantation cure more than 90% of cancer in women, but can result in premature ovarian insufficiency depending on follicular reserve, age, and drugs used. Some benign diseases are also indications for fertility preservation, particularly those requiring chemotherapy (like thalassemia and lupus), recurrent endometriosis, and family history of premature menopause. Social reasons also account for a large proportion of women who wish to postpone pregnancy. This article discusses the two main strategies for fertility preservation, namely oocyte vitrification and ovarian tissue cryopreservation, examining the indications and results of these options. Oocyte cryopreservation is an effective approach, but further studies are needed in cancer patients to ensure the excellent outcomes obtained in women without cancer or in egg donation programs. For prepubertal girls or cases where immediate therapy is required, cryopreservation of ovarian tissue is the only available option.

Added Benefit of Immature Oocyte Maturation for Fertility Preservation in Women with Malignancy.

To assess the added value of maturing immature oocytes collected during fertility preservation treatments in women with malignancy. A retrospective case-control study analyzing the results of 327 cancer patients undergoing fertility preservation treatments. Oocyte maturation rates and cycle parameters were compared between 3 types of fertility preservation treatments: (1) stimulated IVF cycle (n = 143), (2) non-stimulated IVM cycle (n = 158), (3) follicle aspiration and oocyte collection from ovarian tissue prepared for ovarian tissue cryopreservation followed by in vitro maturation of the immature oocytes (n = 48). The primary outcome measure was the maturation rate and the number of mature oocytes. The secondary outcomes were oocyte fertilization and embryo development rates. The mean maturation rate in IVF cycles was 38% and in the non-stimulated IVM cycles was 55%. In women who chose to cryopreserve their embryos, similar fertilization and embryo cleavage rates were found in oocytes that matured after stimulated IVF cycles compared to non-stimulated IVM cycles. Gonadotropin-releasing hormone agonist triggering, treatment with aromatase inhibitor, or oral contraceptives use before the cycle did not affect the maturation rate. Ovarian stimulation yields the highest number of oocytes or embryos for cryopreservation. Although the maturation rate of immature oocytes collected in stimulated IVF cycles is low, it is still a viable source of oocytes that can be used to improve the efficacy of fertility preservation treatments by increasing the number of mature oocytes available for freezing or fertilization.

Future perspectives of fertility preservation in women

SummaryFertility preservation in women has become well established over the last two decades. Nevertheless, options for cancer survivors need to be improved to regain ovarian functioning, ideally leading to pregnancy and live birth. Techniques to protect the ovary from the damage of cytotoxic agents, to improve the survival of follicles in the ovarian graft, and to minimize the risk of re-seeding malignant cells after ovarian tissue transplantation are the object of current research all over the world. The demand for fertility preservation procedures in patients with benign diseases like systemic lupus erythematosus before cytotoxic therapy, in patients with endometriosis before surgery, and in patients with genetic predispositions which can lead to a premature ovarian failure will further increase in coming years. In this short review, these future perspectives are presented.

In vitro ovarian follicle growth: a comprehensive analysis of key protocol variables†.

Folliculogenesis is a complex process that requires integration of autocrine, paracrine, and endocrine factors together with tightly regulated interactions between granulosa cells and oocytes for the growth and survival of healthy follicles. Culture of ovarian follicles is a powerful approach for investigating folliculogenesis and oogenesis in a tightly controlled environment. This method has not only enabled unprecedented insight into the fundamental biology of follicle development but also has far-reaching translational applications, including in fertility preservation for women whose ovarian follicles may be damaged by disease or its treatment or in wildlife conservation. Two- and three-dimensional follicle culture systems have been developed and are rapidly evolving. It is clear from a review of the literature on isolated follicle culture methods published over the past two decades (1980-2018) that protocols vary with respect to species examined, follicle isolation methods, culture techniques, culture media and nutrient and hormone supplementation, and experimental endpoints. Here we review the heterogeneity among these major variables of follicle culture protocols.

Fertility preservation in women affected by gynaecological cancer: the importance of an integrated gynaecological and psychological approach.

Gynaecological cancer treatment significantly affects the fertility of women in reproductive age. Surgery, chemotherapy and radiotherapy are the mainstays of ovarian, cervical and endometrial cancers and anatomically or functionally impact the uterus and ovaries. Moreover, the sexual function and psychological wellbeing of patients are highly weakened after a cancer diagnosis: depression, anxiety and impairment of quality of life represent a relevant concern for patient care. The potential loss of fertility could be more distressing than cancer itself. For this reason, it is of paramount importance to try to preserve fertility in women affected by gynaecological cancers. Recently, tailored fertility preservation therapies have been developed to meet the childbearing demand from more than half of women between 18 and 40 years with a diagnosis of cancer. Currently, fertility preservation techniques play a significant role in improving the quality of life of women with gynaecological cancer. In this scenario, we propose a narrative overview of the recent literature about the importance of a multidisciplinary approach in the management of fertility preservation in the case of gynaecological cancers.