Installing oncofertility programs for breast cancer in limited versus optimum resource settings: Empirical data from 39 surveyed centers in Repro-Can-OPEN Study Part I & II

PurposeAs a further step to elucidate the actual diverse spectrum of oncofertility practices for breast cancer around the globe, we present and discuss the comparisons of oncofertility practices for breast cancer in limited versus optimum resource settings based on data collected in the Repro-Can-OPEN Study Part I & II.MethodsWe surveyed 39 oncofertility centers including 14 in limited resource settings from Africa, Asia & Latin America (Repro-Can-OPEN Study Part I), and 25 in optimum resource settings from the United States, Europe, Australia and Japan (Repro-Can-OPEN Study Part II). Survey questions covered the availability of fertility preservation and restoration options offered to young female patients with breast cancer as well as the degree of utilization.ResultsIn the Repro-Can-OPEN Study Part I & II, responses for breast cancer and calculated oncofertility scores showed the following characteristics: (1) higher oncofertility scores in optimum resource settings than in limited resource settings especially for established options, (2) frequent utilization of egg freezing, embryo freezing, ovarian tissue freezing, GnRH analogs, and fractionation of chemo- and radiotherapy, (3) promising utilization of oocyte in vitro maturation (IVM), (4) rare utilization of neoadjuvant cytoprotective pharmacotherapy, artificial ovary, and stem cells reproductive technology as they are still in preclinical or early clinical research settings, (5) recognition that technical and ethical concerns should be considered when offering advanced and innovative oncofertility options.ConclusionsWe presented a plausible oncofertility best practice model to guide oncofertility teams in optimizing care for breast cancer patients in various resource settings.     

Safety of fertility preservation in breast cancer patients in a register-based matched cohort study

Purpose

To determine if women with breast cancer that undergo fertility preservation (FP), with or without hormonal stimulation, present with an increased risk of breast cancer recurrence.

Methods

A matched cohort study on women with breast cancer attempting to ensure FP in Stockholm from 1999 to 2013 [exposed women (n = 188), age-matched unexposed controls (n = 378)] was designed using the Stockholm regional data from the Swedish National Breast Cancer Quality Register. Breast cancer relapse rates [incidence rate ratio (IRR)] and 95% confidence interval (CI) were estimated using Cox regression and adjusted for potential confounding factors. Completeness of the registry at the time of the study was close to 99%.

Results

Most women attempted FP by hormonal stimulation treatment (n = 148, 79%) with the objective of freezing their eggs or embryos. A smaller group elected FP methods without hormone stimulation (n = 40, 21%). Women who received hormone stimulation did not present with a higher relapse rate than unexposed control women in a model adjusted for age and calendar period of diagnosis (IRR 0.59, 95% CI 0.34–1.04). The results remained virtually unchanged after adjustment for tumor size, estrogen receptor status, affected lymph nodes, and chemotherapy treatment (IRR 0.66, 95% CI 0.37–1.17).

Conclusion

Evidence was not found that fertility preservation, with or without hormonal stimulation, was associated with an increased risk of breast cancer recurrence. The high coverage rate of this population-based study supports the safe practice of fertility preservation in young women with breast cancer.

     

Options on fertility preservation in female cancer patients

Infertility following treatment of cancer is a quality of survival's recognized issue and efforts should be made to help young cancer patients retaining their fertility potential. Options to preserve fertility in female patients include well established methods such as shielding to reduce radiation damage to reproductive organs, fertility-sparing surgery and emergency in vitro fertilization after controlled ovarian stimulation, aiming at freezing embryos. Transfer of frozen/thawed embryos today is a clinical routine in fertility clinics worldwide and it has been used for over 25 years. Mature oocytes after ovarian stimulation can also be frozen unfertilized, nevertheless overall pregnancy rates after fertilization of frozen-thawn oocytes are still relatively lower than those with embryo freezing. Remaining fertility preservation options are still in development and include the freezing of immature oocytes aiming at later in vitro maturing and fertilizing them and the cryopreservation of ovarian tissue for future retransplantation or for in vitro growth and maturation of follicles, both still experimental.     

Recent advances in oocyte and ovarian tissue cryopreservation and transplantation

Options for preserving fertility in women include well-established methods such as fertility-sparing surgery, shielding to reduce radiation damage to reproductive organs, and emergency in-vitro fertilisation after controlled ovarian stimulation, with the aim of freezing embryos. The practice of transfering frozen or thawed embryos has been in place for over 25 years, and today is a routine clinical treatment in fertility clinics. Oocytes may also be frozen unfertilised for later thawing and fertilisation by intracytoplasmic sperm injection in?vitro. In recent years, oocyte cryopreservation methods have further developed, reaching promising standards. More than 1000 children are born worldwide after fertilisation of frozen and thawed oocytes. Nevertheless, this technique is still considered experimental. In this chapter, we focus on options for fertility preservation still in development that can be offered to women. These include freezing of oocytes and ovarian cortex and the transplantation of ovarian tissue.     

Increased incidence of obstetric and perinatal complications in pregnancies achieved using donor oocytes and single embryo transfer in young and healthy women. A prospective hospital-based matched cohort study

In this single-center matched-cohort study, women who underwent IVF/ICSI with donor oocytes between 2007 and 2014 (n?=?259) were compared to women undergoing autologous cycles during the same time period (n?=?515). The matching (1:2) took into consideration the women’s age, type of treatment (IVF/ICSI), and year of embryo transfer. All women were healthy and below 40?years of age at the time of IVF/ICSI, and the treatments were performed using a strict policy of single embryo transfer. Multiple logistic regression analysis, adjusted for body mass index (BMI), smoking, and parity, showed a four times increased risk of gestational hypertensive disorders (adjusted odds ratio, AOR 4.25; 95% confidence interval (CI), 2.61–6.92) and pre-eclampsia (AOR 3.99; 95% CI 2.27–7.00) in pregnancies achieved with donor oocytes. There was also a higher rate of cesarean section in women who gave birth after oocyte donation (AOR 1.69; 95% CI 1.22–2.35) and a higher risk of postpartum hemorrhage >1000?mL (AOR 1.59; 95% CI, 1.11–2.27). After further adjustment for preeclampsia in the logistic regression analysis, no additional increased perinatal risks were found. The incidence of preterm delivery, low weight at birth, need of neonatal intensive care, Apgar scores, and incidence of perinatal death were also similar between the groups.     

Fertility preservation in women with breast cancer

Fertility preservation is an important issue for young women diagnosed with breast cancer. The most well-established options for fertility preservation in cancer patients, embryo and oocyte cryopreservation, have not been traditionally offered to breast cancer patients as estradiol rise during standard stimulation protocols may not be safe for those patients. Potentially safer stimulation protocols using tamoxifen and aromatase inhibitors induce lower levels of estradiol whereas similar results in terms of number of oocyte and embryo obtained to standard protocols. Cryopreservation of immature oocytes and ovarian cortical tissue, both still experimental methods, are also fertility preservation options for breast cancer patients.     

Postoperative AMH reduction is not associated with reduced fecundity two years following ovarian cyst surgery

In a prospective study, we investigated the impact of anti-Müllerian hormone (AMH) changes following ovarian cyst surgery on the probability to achieve pregnancy and live birth. Women of reproductive age (n?=?60) were included before surgery for benign ovarian cysts. Serum AMH concentrations were determined pre- and postoperative at 6 and 24 months. Information regarding pregnancy wish and attempts to conceive were obtained by a questionnaire. At the time of inclusion, 45/60 women reported desire of children. At six months, the levels of AMH decreased significantly in the whole group and further reduction was observed at two years (from 2.7?μg/L to 2.0?μg/L to 1.1?μg/L, respectively, p< 0.008), with a percentage reduction of 42.9%. At two-year follow-up, 36 women reported to have attempted to conceive and 18 achieved pregnancy (50%), with a live birth rate of 33%. The percentage change in AMH at two years did not differ significantly between the women who conceived versus those who did not (p?=?0.117). Data reported herein demonstrate that the AMH reduction following ovarian cyst surgery is maintained two years after surgery; however, the postoperative AMH decrease that follows ovarian cyst surgery might not reduce the chances to achieve pregnancy.