Fertility Preservation in Women With Endometriosis

Infertility affects 30% to 50% of women with endometriosis. Women with endometriosis are at risk of decreased ovarian reserve, both because of the pathophysiology of the disease and iatrogenic injury resulting from surgical intervention. Fertility preservation must occur at multiple levels, including careful selection of surgical candidates, avoidance of repeat procedures, and meticulous surgical technique. Fertility preservation with oocyte or ovarian tissue cryopreservation may be considered on an individual basis for women with endometriosis, particularly those at risk of bilateral ovarian injury, such as women with bilateral endometriomas.

Setting Up a Cryopreservation Programme for Immature Testicular Tissue: Lessons Learned After More Than 15 Years of Experience

Young boys undergoing gonadotoxic treatments are at high risk of spermatogonial stem cell (SSC) loss and fertility problems later in life. Stem cell loss can also occur in specific genetic conditions, eg, Klinefelter syndrome (KS). Before puberty, these boys do not yet produce sperm. Hence, they cannot benefit from sperm banking. An emerging alternative is the freezing of testicular tissue aiming to preserve the SSCs for eventual autologous transplantation or in vitro maturation at adult age. Many fertility preservation programmes include cryopreservation of immature testicular tissue, although the restoration procedures are still under development. Until the end of 2018, the Universitair Ziekenhuis Brussel has frozen testicular tissues of 112 patients between 8 months and 18 years of age. Testicular tissue was removed in view of gonadotoxic cancer treatment (35%), gonadotoxic conditioning therapy for bone marrow transplantation (35%) or in boys diagnosed with KS (30%). So far, none of these boys had their testicular tissue transplanted back. This article summarizes our experience with cryopreservation of immature testicular tissue over the past 16 years (2002-2018) and describes the key issues for setting up a cryopreservation programme for immature testicular tissue as a means to safeguard the future fertility of boys at high risk of SSC loss.

Ovarian Function and Fertility Preservation in Breast Cancer: Should Gonadotropin-Releasing Hormone Agonist be administered to All Premenopausal Patients Receiving Chemotherapy?

Chemotherapy-induced premature ovarian insufficiency (POI) is one of the potential drawbacks of chemotherapy use of particular concern for newly diagnosed premenopausal breast cancer patients. Temporary ovarian suppression obtained pharmacologically with the administration of a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy has been specifically developed as a method to counteract chemotherapy-induced gonadotoxicity with the main goal of diminishing the risk of POI. In recent years, important clinical evidence has become available on the efficacy and safety of this strategy that should now be considered a standard option for ovarian function preservation in premenopausal breast cancer patients, including women who are not interested in conceiving after treatment or that would not be candidates for fertility preservation strategies because of their age. Nevertheless, in women interested in fertility preservation, this is not an alternative to gamete cryopreservation, which remains as the first option to be offered. In this setting, temporary ovarian suppression with GnRHa during chemotherapy should be also proposed following gamete cryopreservation or to women who have no access, refuse, or have contraindications to surgical fertility preservation techniques. In this article, we present an overview about the role of temporary ovarian suppression with GnRHa during chemotherapy in breast cancer patients by addressing the available clinical evidence with the aim of identifying both the best candidates for the use of this strategy and the still existing gray zones requiring further investigation.

PCOS and Hyperprolactinemia: what do we know in 2019?

Polycystic ovary syndrome (PCOS) and hyperprolactinemia (HPRL) are the two most common etiologies of anovulation in women. Since the 1950s, some authors think that there is a pathophysiological link between PCOS and HPRL. Since then, many authors have speculated about the link between these two endocrine entities, but no hypothesis proposed so far could ever be confirmed. Furthermore, PCOS and HPRL are frequent endocrine diseases and a fortuitous association cannot be excluded. The evolution of knowledge about PCOS and HPRL shows that studies conducted before the 2000s are obsolete given current knowledge. Indeed, most of the studies were conducted before consensual diagnosis criteria of PCOS and included small numbers of patients. In addition, the investigation of HPRL in these studies relied on obsolete methods and did not look for the presence of macroprolactinemia. It is therefore possible that HPRL that has been attributed to PCOS corresponded in fact to macroprolactinemia or to pituitary microadenomas of small sizes that could not be detected with the imaging methods of the time. Recent studies that have conducted a rigorous etiological investigation show that HPRL found in PCOS correspond either to non-permanent increase of prolactin levels, to macroprolactinemia or to other etiologies. None of this recent study found HPRL related to PCOS in these patients. Thus, the link between PCOS and HPRL seems to be more of a myth than a well-established medical reality and we believe that the discovery of an HPRL in a PCOS patient needs a standard etiological investigation of HPRL.

Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo

Historically, approaches designed to offer women diagnosed with cancer the prospects of having a genetically matched child after completion of their cytotoxic treatments focused on the existing oocyte population as the sole resource available for clinical management of infertility. In this regard, elective oocyte and embryo cryopreservation, as well as autologous ovarian cortical tissue grafting posttreatment, have gained widespread support as options for young girls and reproductive-age women who are faced with cancer to consider. In addition, the use of ovarian protective therapies, including gonadotropin-releasing hormone agonists and sphingosine-1-phosphate analogs, has been put forth as an alternative way to preserve fertility by shielding existing oocytes in the ovaries in vivo from the side-effect damage caused by radiotherapy and many chemotherapeutic regimens. This viewpoint changed with the publication of now numerous reports that adult ovaries of many mammalian species, including humans, contain a rare population of oocyte-producing germ cells—referred to as female germline or oogonial stem cells (OSCs). This new line of study has fueled research into the prospects of generating new oocytes, rather than working with existing oocytes, as a novel approach to sustain or restore fertility in female cancer survivors. Here, we overview the history of work from laboratories around the world focused on improving our understanding of the biology of OSCs and how these cells may be used to reconstitute “artificial” ovarian tissue in vitro or to regenerate damaged ovarian tissue in vivo as future fertility-preservation options.

FertiPROTEKT, Oncofertility Consortium and the Danish Fertility-Preservation Networks – What Can We Learn From Their Experiences?

Fertility preservation is an increasingly important discipline. It requires close coordination between reproductive medicine specialists, reproductive biologists, and oncologists in various disciplines. In addition, it represents a particular health policy challenge, since fertility-protection measures are to be understood as a treatment for side effects of gonadotoxic treatments and would therefore normally have to be reimbursed by health insurance companies. Therefore, it is inevitable that fertility-preservation activities should organise themselves into a network structure both as a medical-logistic network and as a professional medical society. The necessary network structures can differ significantly at regional, national, and international level, as the size of the regions to be integrated and the local cultural and geographical conditions, as well as the political conditions are very different. To address these issues, the current review aims to point out the basic importance and the chances but also the difficulties of fertility-protection networks and give practical guidance for the development of such network structures. We will not only discuss network structures theoretically but also present them based on three established, different sized networks, such as the Danish Network ( www.rigshospitalet.dk ), representing a centralised network in a small country; the German-Austrian-Swiss network FertiPROTEKT® ( www.fertiprotekt.com ), representing a centralised as well as decentralised network in a large country; and the Oncofertility® Consortium ( www.oncofertility.northwestern.edu ), representing a decentralised, internationally oriented network, primarily serving the transfer of knowledge among its members.

To Get Back on Track: A Qualitative Study on Childless Women’s Expectations on Future Fertility Before Undergoing Bariatric Surgery

Background: In Sweden, 4700 women seek bariatric surgery annually, many of those being nulliparous. Anovulation is common among obese women, but bariatric surgery is not considered a treatment for infertility. The aim of this study was to explore the motives of women in fertile age for seeking bariatric surgery and their expectations on future fertility. Materials and methods: A qualitative study with semi-structured interviews with childless women ( n = 12) aged 20 to 35 years. Interviews were conducted 1 to 3 weeks prior to surgery, transcribed verbatim, and analyzed with thematic analysis. Results: “To get back on track” was identified as a master theme with 3 underlying subthemes, with the following headings: “A better me,” “A fertile me,” and “A pregnant me.” The participants were hoping that weight-loss would make them feel more content with themselves, break isolation, and make it easier to find a partner. The participants considered fertility to improve after bariatric surgery, mainly based on stories from other patients of bariatric surgery. Having a child was expressed to be of great importance to them. Conclusions: Even though obese young women do not seek bariatric surgery for fertility reasons alone, there is a general perception of enhanced fertility after surgery, which is regarded as positive and important.

The Source of Polycystic Ovarian Syndrome

The source of polycystic ovarian syndrome (PCOS) is much debated and is likely to be multifactorial. There is an apparent familial inheritance with first-degree relatives of sufferers more likely to be affected. Twin studies have suggested a genetic cause but candidate genes are yet to be verified. Genes affecting insulin resistance, steroid hormone production, and inflammatory cytokine responses have all been implicated. Current thinking supports the theory that exposure to environmental factors in utero predisposes a female foetus to hyperandrogenism, insulin resistance, and polycystic ovaries in adult life. Which environmental factors have an impact on the foetus and the mechanisms of exposure are still to be confirmed. Animal studies have shown a clear correlation between hyperexposure of the foetus to androgens in utero and future development of a PCOS pattern of symptoms. Placental aromatases should neutralise androgens from the maternal circulation and prevent them reaching the foetal circulation. Our hypothesis is that the high maternal anti-Mullerian hormone (AMH) levels in PCOS block the placental aromatase and allow passage of testosterone through the placenta. This maternal testosterone acts on the foetal ovaries and ‘programmes’ them to recruit more preantral follicles and so produce higher AMH levels when they become functional at around 36 weeks of gestation. The high AMH concentrations in PCOS also seem to increase luteinizing hormone release and inhibit follicle stimulating hormone action on aromatase, so adding to the hyperandrogenic environment of adult PCOS.

An Exploratory Analysis of Factors Associated With Interest in Postpartum Intrauterine Device Uptake Among Pregnant Women and Couples in Kigali, Rwanda

Background: The desire to space or prevent future pregnancies is high among postpartum women in Rwanda. However, the use of long-acting reversible contraception (LARC), especially the highly effective and cost-effective copper intrauterine device (IUD), is very low, whereas the rates of unintended pregnancy are high. This study aims to identify factors associated with pregnant women’s and couple’s interest in receiving a postpartum intrauterine device (PPIUD) within 6 weeks after delivery. Methods: A total of 150 pregnant women or couples attending antenatal care (ANC) in Kigali, Rwanda participated in this cross-sectional study. After participating in a postpartum LARC counseling session, surveys assessed participants’ demographics, pregnancy experiences and desires, and PPIUD knowledge, attitudes, practices, and interest. Multivariable logistic regression was used to model factors associated PPIUD interest within 6 weeks postpartum. Results: Although only 3% of women had ever used an IUD previously, 124 (83%) women were interested in receiving a PPIUD after counseling. Self-reporting physical side effects (adjusted odds ratio [aOR], 0.21; 95% confidence interval [CI], 0.06-0.75) and infection (aOR, 0.19; 95% CI, 0.04-0.85) as disadvantages to the IUD were significantly associated with no interest in receiving a PPIUD. Interest did not differ by male involvement. Conclusion: Recommendations to increase PPIUD uptake include educating pregnant women and couples about the method during ANC and addressing client myths and misconceptions about the IUD. This strategy allows pregnant women and couples to make informed decisions about their future contraception use, reduce unmet need for family planning, and reduce unintended pregnancy.

Fertility Preservation Using GnRH Agonists: Rationale, Possible Mechanisms, and Explanation of Controversy

The only clinically accepted method of fertility preservation in young women facing gonadotoxic chemo- and/or radiotherapy for malignant or autoimmune diseases is cryopreservation of embryos or unfertilized ova, whereas cryopreservation of ovarian tissue for future reimplantation, or in vitro maturation of follicles, and the use of gonadotropin-releasing hormone agonists (GnRHa) are still considered investigational, by several authorities. Whereas previous publications have raised the fear of GnRHa’s possible detrimental effects in patients with hormone receptor-positive breast cancers, recent randomized controlled trials (RCTs) have shown that it either improves or does not affect disease-free survival (DFS) in such patients. This review summarizes the pros and cons of GnRHa co-treatment for fertility preservation, suggesting 5 theoretical mechanisms for GnRHa action: (1) simulating the prepubertal hypogonadotropic milieu, (2) direct effect on GnRH receptors, (3) decreased ovarian perfusion, (4) upregulation of an ovarian-protecting molecule such as sphingosine-1-phosphate, and (5) protecting a possible germinative stem cell. We try to explain the reasons for the discrepancy between most publications that support the use of GnRHa for fertility preservation and the minority of publications that did not support its efficiency.