A prospective study of women and girls undergoing fertility preservation due to oncologic and non-oncologic indications in Sweden-Trends in patients' choices and benefit of the chosen methods after long-term follow up.

INTRODUCTION: In Scandinavian countries, programs for fertility preservation are offered free of charge at tertiary-care university hospitals to all patients facing treatments with risk of subsequent sterility. In this prospective study we aimed to investigate trends in female patients' choices after counseling and fertility preservation outcomes during follow up in relation to benign vs malignant indications. MATERIAL AND METHODS: Data on 1254 females including 1076 adults and 178 girls who received fertility preservation counseling for either oncologic (n = 852) or benign indications (n = 402) at Karolinska University Hospital, Stockholm, between 1 October 1998 and 1 December 2018 were analyzed. As appropriate, t tests and chi-square tests were used to compare groups. Logistic regression was used to compare outcomes among groups depending on indications. RESULTS: Adult women generally elected to undergo oocyte retrieval after controlled ovarian stimulation for cryopreservation of embryos or oocytes (n = 538, 73%), whereas a minor proportion opted for cryopreservation of ovarian tissue retrieved through laparoscopy (n = 221, 27%). More than half of the women with a partner chose either not to fertilize their oocytes aiming at cryopreservation of oocytes or to share obtained oocytes attempting both cryopreservation of oocytes and cryopreservation of embryos. All pre-pubertal (n = 48) and 73% of post-pubertal girls (n = 66) elected cryopreservation of ovarian tissue. In recent years, an increasing number of teenagers have opted for controlled ovarian stimulation aiming at cryopreservation of oocytes, either before (n = 24, 17%) or after completion of cancer treatment (n = 15, 10%). During follow up, 27% of the women returned for a new reproductive counseling, additional fertility preservation or to attempt pregnancy. Utilization rates among individuals who were alive and of childbearing age by December 2018 indicated 29%, 8% and 5% for embryos, oocytes and ovarian tissue with live birth rates of 54%, 46% and 7%, respectively. Women with benign indications were significantly younger than women with previous malignant indications at the time of attempting pregnancy. Although the pregnancy rates were similar among both groups, the live birth rate was significantly higher in women with benign vs previous malignant indications (47% vs 21%, P = .002). CONCLUSIONS: Trends in fertility preservation choices have changed over time. Women with previous malignancy had lower live birth rates than women with benign fertility preservation indications.

Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study.

STUDY QUESTION: Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? SUMMARY ANSWER: A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. WHAT IS KNOWN ALREADY: Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. STUDY DESIGN, SIZE, DURATION: This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. MAIN RESULTS AND THE ROLE OF CHANCE: The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P = <0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = <0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i.e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. WIDER IMPLICATIONS OF THE FINDINGS: To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Not applicable.

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.

Anti-Müllerian hormone reduction after ovarian cyst surgery is dependent on the histological cyst type and preoperative anti-Müllerian hormone levels.

OBJECTIVE: To investigate changes in serum anti-Müllerian hormone (AMH) concentrations following ovarian cyst surgery, and predictors of these changes. DESIGN: Prospective cohort study with follow up at 3 and 6 months. SETTING: University hospital. POPULATION: Women of reproductive age scheduled for ovarian cyst surgery. METHODS: Women were recruited between March 2011 and March 2012 (n = 75). Serum AMH concentrations were measured preoperatively and at 3 and 6 months postoperatively. MAIN OUTCOME MEASURES: Changes in AMH after surgery and predictors for these changes. RESULTS: After surgery, median AMH levels decreased significantly from 2.7 µg/L (0.2-16.9) to 1.6 µg/L (0.2-9.9) at 3 months and were still low, 1.6 µg/L (0.2-8.3) at 6 months (both p < 0.001). In patients with unilateral cysts, a significant and more rapid AMH decrease was seen after enucleation of endometriomas (n = 19) vs. dermoid cysts (n = 22) (p = 0.010). The reduction was long-lasting at 6 months. In a multivariate regression analysis, a higher baseline AMH concentration was predictive of AMH reduction at 3 [odds ratio (OR) 1.9, 95% CI 1.1-3.1] and 6 months postoperatively (OR 2.5, 95% CI 1.2-5.2). Women with normal or elevated baseline AMH presented with a significant reduction of -23% and -43% at 3 and 6 months, respectively, whereas women with low or very low AMH had minimal or no changes over time. Patient's age, cyst size, duration of surgery or intraoperative bleeding were not predictive of a postoperative AMH decrease. CONCLUSIONS: Reduction of AMH was of greater magnitude and longer duration after enucleation of endometriomas and in women with normal and high preoperative AMH levels.

Young women's perceptions of fertility-related information and fertility distress before surgery for ovarian cysts.

OBJECTIVE: To investigate young women's reproductive desire and perceptions of fertility-related information when scheduled for ovarian cyst surgery with a possible impact on fertility. DESIGN: Cross-sectional study. SETTING: University Hospital. POPULATION: Women of reproductive age (n = 106, mean age 32.3 years, range 18-44 years) with a diagnosis of ovarian cyst and scheduled ovarian cyst surgery between March 2011 and September 2012 were included. METHODS: The women answered a questionnaire after the presurgery consultation with the gynecologist. The questionnaire included study-specific measures of reproductive desire, perception of fertility-related information received, worry about future fertility and sociodemographic characteristics. MAIN OUTCOME MEASURE: Reproductive desire and recalled information on the impact of surgery on fertility. RESULTS: A high proportion of the women (72%) reported a desire for having children in the future and more than half of them (58%) recalled receiving information about the impact of surgery on fertility. In a multivariable logistic regression model adjusted for parity, education and age, a desire to have children increased the likelihood of recalling having received fertility-related information (odds ratio 3.2, 95% CI 1.1-9.2). CONCLUSIONS: Almost half of women with reproductive desire had ovarian surgery without recalling a discussion of fertility issues. Development of written information or interactive information might improve women's perception of fertility-related information.

Live birth and pregnancy rates after in vitro fertilization/intracytoplasmic sperm injection in women with previous unilateral oophorectomy: a systematic review and meta-analysis.

OBJECTIVE: To quantify the effect of unilateral oophorectomy (UO) on the rates of live birth and pregnancy in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). DESIGN: Systematic review and meta-analysis. SETTING: Search of databases of published articles. PATIENT(S): The final analytical cohort encompassed 1,057 IVF/ICSI cycles in women with previous UO and 45,813 IVF/ICSI cycles in control women. Eighteen studies were identified by database searches of MEDLINE, Embase, Web of Science, and cited references. The review encompassed studies published up to June 1, 2021. INTERVENTION(S): UO prior to IVF/ICSI. MAIN OUTCOME MEASURE(S): The primary outcomes were the rates of live birth and pregnancy following IVF/ICSI. The secondary outcomes included the amount of gonadotropins administered for ovarian stimulation and the number of retrieved oocytes. RESULT(S): The studies were rated from medium to high quality (from 5 to 8) according to the Newcastle-Ottawa Quality Assessment Scale. All studies were observational, with inherent bias, and heterogeneity was high. The primary outcome of live birth had a significantly lower odds ratio (OR) in women with previous UO compared with controls (OR = 0.72, 95% confidence interval [CI] 0.57 to 0.91, z = -2.72). The OR for pregnancy rate per initiated treatment cycle was also significantly lower in women with previous UO compared with controls (OR = 0.70, 95% CI 0.57 to 0.86, z = -3.35). Additionally, the dose of administered gonadotropins was significantly higher and the number of retrieved oocytes was significantly lower in women with UO. CONCLUSION(S): The meta-analysis showed a significant detrimental effect of UO on the rates of live birth and pregnancy. The analysis further supports previous data showing a decreased sensitivity to gonadotropins and a lower number of recovered oocytes in women with previous UO. STUDY REGISTRATION NUMBER: PROSPERO 2020, CRD42020160313.