Cumulative Incidence Of Pregnancy Research Articles

Abstract GS02-11: Fertility preservation and assisted reproductive technologies (ART) in breast cancer (BC) patients (pts) interrupting endocrine therapy (ET) to attempt pregnancy

Abstract Background: The POSITIVE trial recently demonstrated that temporary interruption of ET to attempt pregnancy does not increase the short-term risk of recurrence in pts with hormone receptor-positive (HR+) BC. Yet, uncertainty exists regarding the safety of ovarian stimulation for embryo/oocyte cryopreservation to preserve fertility in these pts. In addition, very limited data exist regarding safety and efficiency of ART to achieve pregnancy after ET interruption. Methods: POSITIVE is an international, single-arm, prospective trial that enrolled pts ≤ 42 years with stage I-III HR+ BC who had already received 18-30 months of ET prior to enrollment. The use of ART was a predefined 2ry endpoint. We evaluated factors associated with time to pregnancy in a Fine and Gray competing risks model, which included chemotherapy (chemo) ± GnRH analogue (GnRHa), age, prior ET, prior birth, and menstrual status at enrollment. The cumulative incidence of pregnancy at 12 months from enrollment by age was estimated controlling for competing risks. We performed a logistic regression model to evaluate whether ART use was associated with achieving pregnancy, adjusting for age, receipt of chemo ± GnRHa. The cumulative incidence of BCFI events was estimated according to whether or not ovarian stimulation for cryopreservation was performed at diagnosis and prior to enrollment. BC-free interval (BCFI) was defined as the time from enrollment until the first BC event (invasive local, regional, or distant recurrence or contralateral disease). A 24-month landmark analysis was performed to investigate the safety of ART use after enrollment. Median follow-up was 41 months. Results: 497 out of 516 included pts (96%) were followed for at least 6 months and were evaluable for pregnancy status. 368 out of 497 evaluable pts (74%) reported at least one pregnancy. In a multivariable model, young age was the only factor associated with shorter time to pregnancy. The cumulative incidence of pregnancy at 12 months was 64%, 54% and 38% for pts aged < 35, 35-39 and 40-42 years, respectively. 179 pts (36.0%) had undergone ovarian stimulation for embryo/oocyte cryopreservation at diagnosis and prior to enrollment, of whom 68 (37.9%) reported cryopreserved embryo transfer after enrollment. 215 pts (43.3%) reported using any ART after enrollment, of whom 80 (37.2%) underwent ovarian stimulation for in-vitro fertilization (FIVET) or intracytoplasmic sperm injection (ICSI). Other ART used included clomiphene (n=19), intrauterine insemination (n=37) and egg donation (n=17). Pregnancy rates were 82.4% and 67.5% for women who underwent cryopreserved embryo transfer and FIVET/ICSI, respectively. In a multivariate model, cryopreserved embryo transfer was the only ART independently associated with a higher chance of pregnancy (OR:2.41, 95% CI: 1.75-4.95). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis and before enrollment, 9.7% (95% CI: 6.0-15.4%), and those who did not, 8.7% (95% CI: 6.0-12.5%). A 24-month landmark analysis showed no impact of ovarian stimulation for FIVET/ICSI after enrollment on BCFI. Conclusions: This is the largest prospective study to investigate fertility preservation and ART in pts with HR+ BC. Young age was the main factor associated with shorter time to pregnancy. Embryo/oocyte cryopreservation at BC diagnosis followed by embryo transfer after ET interruption was the only approach associated with an increased chance of pregnancy. Ovarian stimulation either at BC diagnosis for embryo/oocyte cryopreservation or after enrollment to POSITIVE for FIVET/ICSI did not appear to impact prognosis in the short term. These data are of paramount importance for oncofertility counselling of young BC pts. Citation Format: Hatem Azim, Samuel Niman, Ann Partridge, Isabelle Demeestere, Monica Ruggeri, Marco Colleoni, Cristina Saura, Chikako Shimizu, Anna Saetersdal, Judith Kroep, Audrey Mailliez, Ellen Warner, Virginia Borges, Frédéric Amant, Andrea Gombos, Akemi Kataoka, Christine Rousset-Jablonski, Simona Borstnar, Junko Takei, Jeong Eon Lee, Janice Walshe, Manuel Ruíz - Borrego, Halle Moore, Christobel Saunders, Vesna Bjelic-Radisic, Snezana Susnjar, Fatima Cardoso, Natalie Klar, Tanya Spanic, Kathryn Ruddy, Martine Piccart, Larissa Korde, Aron Goldhirsch, Richard Gelber, Olivia Pagani, Fedro Alessandro Peccatori. Fertility preservation and assisted reproductive technologies (ART) in breast cancer (BC) patients (pts) interrupting endocrine therapy (ET) to attempt pregnancy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-11.

Fertility outcomes several years after urgent fertility preservation for breast cancer patients

To study the fertility outcomes of women who tried to conceive after breast cancer treatment and fertility preservation. Retrospective observational, bicentric cohort study. All patients who had undergone fertility preservation before breast cancer treatment between January 2013, and July 2019 were included (n=844). The end-point date was March 1, 2022. Patients with missing data on pregnancy attempts after cancer diagnosis (n=195) were excluded from the pregnancy analysis. Cumulative incidences of pregnancy and live birth were calculated. For women who became pregnant, the time to conception was calculated between the first fertility preservation consultation and the estimated day of conception. For those who did not conceive, we considered the time between first fertility preservation consultation and the end-point date or the date of patient death. A Cox regression model was used to study the predictive factors of pregnancy and live birth. Among the 649 patients with available data on pregnancy attempts after breast cancer diagnosis, 255 (39.3% [35.5-43.2]) tried to conceive (median follow-up 6.5 years). Overall, 135 (52.9% [46.6-59.2]) of these patients achieved a pregnancy, mainly through unassisted conception (79.3% [72.8-84.8]), and 99 reported a live birth (representing 38.8% of patients who attempted conception). In our cohort, 48 months after the first fertility preservation consultation, the cumulative incidence of pregnancy was 33.1% ([27.6-37.9]). After adjustment for age, parity, type of chemotherapy administration and endocrine therapy, only multiparity at diagnosis and absence of chemotherapy were positive predictive factors of pregnancy after cancer. Of the 793 patients who had vitrified oocytes/embryos, 68 used them (27% [21.3-32.5] of the patients who tried to conceive), resulting in 8 live births (11.8% [5.2-21.9]). Women who used their cryopreserved oocytes/embryos were older at the first consultation of fertility preservation (HR 1.71(1.42-2.21)), and chose more often to vitrify embryos (HR 1.76(1.28-2.23). Although pregnancy rates after fertility preservation for breast cancer are low, most conceptions are achieved without medical assistance. Our findings provide useful information to advise women on the different techniques of fertility preservation, their efficacy and safety, as well as the relatively high chances of unassisted conception.

Pregnancy After Breast Cancer in Young BRCA Carriers

Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Pregnancy after breast cancer. Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. ClinicalTrials.gov Identifier: NCT03673306.

O-084 Fertility outcomes several years after urgent fertility preservation (FP) for breast cancer

Abstract Study question What are the fertility outcomes of women who tried to conceive after breast cancer treatment and FP? Summary answer Three to-ten years after FP for breast cancer, less than half of patients tried to conceive but 39% of them had a child, mainly spontaneously. What is known already Breast cancer is the most common cancer in women of childbearing age. Because of the gonadal toxicity of treatments and temporary contraindication to pregnancy, fertility after cancer treatment is often impaired. Different FP techniques can be offered. Although it is well established that pregnancy in breast cancer survivors is safe, little is known on the incidence of pregnancies after breast cancer treatments in women having undergone FP, the way those patients conceived and outcomes. Study design, size, duration This is a retrospective observational, bicentric cohort study. All patients having undergone FP before breast cancer treatment (oocyte and/or embryo vitrification after controlled ovarian stimulation (COS) or in vitro maturation and/or ovarian tissue cryopreservation) between January 1, 2013 and July 31, 2019 were included (n = 844). Patients for whom data on post-cancer pregnancy attempt was missing (n = 195) were excluded from the analysis of pregnancies.The cut-off date was March 1, 2022. Participants/materials, setting, methods For women who got pregnant, the time to conception was calculated between the 1st FP consultation (CS1) and the day of the estimated conception. For those who did not conceived, we considered the time between the CS1 and the cut-off date or the date of patient’s death. Cumulative incidences of pregnancy and live birth were calculated. A logistic regression Cox model was performed to study the predictive factors of pregnancy and live birth. Main results and the role of chance Among the 649 patients with available data on post-cancer pregnancy attempt, 255 (39.3%) tried to conceive. Overall, 135 (52.9%) of them achieved a pregnancy, mainly spontaneously (79.3%), and 99 (38.8%) reported a live birth. At the CS1, 76.3% of women were in couple and 42.3% already had at least a child. The mean age at CS1 was 32±4.2 years. Invasive ductal carcinoma was the diagnosis in 95.8% of women and 45.7% had COS for FP. In our cohort, 48 months after CS1, the cumulative incidence of pregnancy was 33.1% (CI95% [27.6-37.9]). After adjustment on age, parity, type of chemotherapy and hormonotherapy, only multiparity at diagnosis and absence of chemotherapy were found to be positive predictive factors of pregnancy after cancer. Only multiparity was found to be negatively associated with live birth (RR0.47 [0.33-0.67]). Of the 793 patients who vitrified oocytes/embryos, 68 reused them (26.6% of the patients who tried to conceive) and obtained 8 live births. Women using their cryopreserved biological material were older at CS1, had lower ovarian reserve parameters and had vitrified embryos. Ovarian reserve parameters and number of cryopreserved oocytes were higher while age at CS1 was lower in patients reporting a live birth after oocyte/embryo thawing. Limitations, reasons for caution Due to the retrospective nature of the study, some data is missing. Even if the median follow-up is more than 4 years, a longer follow-up is necessary Wider implications of the findings Although pregnancy rates after breast cancer are reduced, most of conceptions are achieved spontaneously. Our findings provide useful information to advise women on the different techniques of FP, their efficacy and safety. Trial registration number Not applicable

Association of male fatty acid intake with fecundability among couples planning pregnancy.

To what extent is male fatty acid intake associated with fecundability among couples planning pregnancy? We observed weak positive associations of male dietary intakes of total and saturated fatty acids with fecundability; no other fatty acid subtypes were appreciably associated with fecundability. Male fatty acid intake has been associated with semen quality in previous studies. However, little is known about the extent to which male fatty acid intake is associated with fecundability among couples attempting spontaneous conception. We conducted an internet-based preconception prospective cohort study of 697 couples who enrolled during 2015-2022. During 12 cycles of observation, 53 couples (7.6%) were lost to follow-up. Participants were residents of the USA or Canada, aged 21-45 years, and not using fertility treatment at enrollment. At baseline, male participants completed a food frequency questionnaire from which we estimated intakes of total fat and fatty acid subtypes. We ascertained time to pregnancy using questionnaires completed every 8 weeks by female participants until conception or up to 12 months. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs for the associations of fat intakes with fecundability, adjusting for male and female partner characteristics. We used the multivariate nutrient density method to account for energy intake, allowing for interpretation of results as fat intake replacing carbohydrate intake. We conducted several sensitivity analyses to assess the potential for confounding, selection bias, and reverse causation. Among 697 couples, we observed 465 pregnancies during 2970 menstrual cycles of follow-up. The cumulative incidence of pregnancy during 12 cycles of follow-up after accounting for censoring was 76%. Intakes of total and saturated fatty acids were weakly, positively associated with fecundability. Fully adjusted FRs for quartiles of total fat intake were 1.32 (95% CI 1.01-1.71), 1.16 (95% CI 0.88-1.51), and 1.43 (95% CI 1.09-1.88) for the second, third, and fourth vs the first quartile, respectively. Fully adjusted FRs for saturated fatty acid intake were 1.21 (95% CI 0.94-1.55), 1.16 (95% CI 0.89-1.51), and 1.23 (95% CI 0.94-1.62) for the second, third, and fourth vs the first quartile, respectively. Intakes of monounsaturated, polyunsaturated, trans-, omega-3, and omega-6 fatty acids were not strongly associated with fecundability. Results were similar after adjustment for the female partner's intakes of trans- and omega-3 fats. Dietary intakes estimated from the food frequency questionnaire may be subject to non-differential misclassification, which is expected to bias results toward the null in the extreme categories when exposures are modeled as quartiles. There may be residual confounding by unmeasured dietary, lifestyle, or environmental factors. Sample size was limited, especially in subgroup analyses. Our results do not support a strong causal effect of male fatty acid intakes on fecundability among couples attempting to conceive spontaneously. The weak positive associations we observed between male dietary fat intakes and fecundability may reflect a combination of causal associations, measurement error, chance, and residual confounding. The study was funded by the National Institutes of Health, grant numbers R01HD086742 and R01HD105863. In the last 3 years, PRESTO has received in-kind donations from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility app). L.A.W. is a consultant for AbbVie, Inc. M.L.E. is an advisor to Sandstone, Ro, Underdog, Dadi, Hannah, Doveras, and VSeat. The other authors have no competing interests to report. N/A.

Pregnancy Intention, Changes in Pregnancy Intention, and Pregnancy Incidence Among Female Nurses in North America

Pregnancy intention assessment is a key element of preconception and contraceptive care. The association between a single screening question and the incidence of pregnancy is unknown. To prospectively evaluate the dynamics of pregnancy intention and pregnancy incidence. This prospective cohort study (the Nurses' Health Study 3) was conducted from June 1, 2010, to April 1, 2022, in 18 376 premenopausal, nonpregnant female nurses aged 19 to 44 years. Pregnancy intention and pregnancy status were assessed at baseline and approximately every 3 to 6 months thereafter. Cox proportional hazards regression models were used to estimate the association between pregnancy intention and pregnancy incidence. A total of 18 376 premenopausal, nonpregnant women (mean [SD] age, 32.4 [6.5] years) participated in the study. At baseline, 1008 women (5.5%) were trying to conceive, 2452 (13.3%) were contemplating pregnancy within 1 year, and the remaining 14 916 (81.2%) were neither trying to conceive nor thought they would be pregnant within 1 year. A total of 1314 pregnancies were documented within 12 months of pregnancy intention assessment. The cumulative incidence of pregnancy was 38.8% in women actively trying to conceive (median [IQR] time to pregnancy, 3.3 [1.5-6.7] months), 27.6% in women contemplating pregnancy (median [IQR] time to pregnancy, 6.7 [4.2-9.3] months), and 1.7% in women neither trying to conceive nor contemplating pregnancy (median [IQR] time to pregnancy, 7.8 [5.2-10.5] months) among those who became pregnant. Women who were actively trying to conceive were 23.1 times (95% CI, 19.5-27.4 times) and women who were contemplating pregnancy were 13.0 times (95% CI, 11.1-15.2 times) more likely to conceive within 12 months than women who were neither attempting nor contemplating pregnancy. Among women contemplating pregnancy at baseline who did not get pregnant during follow up, 18.8% were actively trying and 27.6% were not trying by 12 months. Conversely, only 4.9% of women neither trying to conceive nor contemplating pregnancy within 1 year at baseline changed pregnancy intention during follow up. In this cohort study of reproductive-aged nurses in North America, pregnancy intention was highly fluid among women who were contemplating pregnancy but relatively stable among women trying to conceive and women who were neither trying to conceive nor contemplating pregnancy. Pregnancy intention was strongly associated with pregnancy incidence, but the median time to pregnancy points to a relatively short time window to initiate preconception care.

Final analysis of the PROMISE-GIM6 phase III trial assessing GnRH agonist use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer.

516 Background: Current guidelines recommend GnRH agonist (GnRHa) use during chemotherapy (CT) as a strategy to reduce the risk of premature ovarian insufficiency (POI) in premenopausal patients with early breast cancer (EBC). However, no long-term safety data are available raising some concerns on concurrent use of GnRHa during CT in patients with hormone receptor-positive disease. In addition, there is no evidence on the protective role of this strategy in patients with germline BRCA mutations ( mBRCA). Here, we report the final analysis of the PROMISE-GIM6 phase III randomized study, the largest trial addressing the role of GnRHa use during CT in premenopausal EBC patients (Del Mastro et al, JAMA 2011 & Lambertini et al, JAMA 2015). Methods: From October 2003 to January 2008, 281 premenopausal patients aged 18 to 45 years with stage I-III EBC candidates for (neo)adjuvant CT were randomized to receive CT alone or combined with the GnRHa triptorelin. Primary endpoint was incidence of CT-induced POI (defined as amenorrhea and post-menopausal FSH/estradiol levels 1 year following CT). This final analysis reports on post-treatment pregnancies, disease-free survival (DFS) and overall survival (OS). An exploratory descriptive analysis in mBRCA patients is also reported. (ClinicalTrial.gov: NCT00311636) Results: Of the 281 randomized patients (CT+GnRHa arm = 148; CT alone arm = 133), 80% had hormone receptor-positive disease. At the time of this final analysis, 38 (13.5%) patients were lost to follow-up. Median follow-up was 12.4 years (IQR: 11.3-13.2 years). In the CT+GnRHa and CT alone arms, respectively, 9 (10-year cumulative incidence of pregnancy 6.5%, 95% CI 3.5%-12.3%) and 4 (10-year cumulative incidence of pregnancy 3.2%, 95% CI 1.2%-8.3%) patients had a post-treatment pregnancy (HR 2.14, 95% CI 0.66-6.92). No differences in 10-year DFS (72.4% in CT+GnRHa arm vs. 71.2% in CT alone arm: HR 1.16, 95% CI 0.76-1.77) nor in 10-year OS (82.0% in CT+GnRHa arm vs. 85.9% in CT alone arm: HR 1.17, 95% CI 0.67-2.03) were observed. There was no interaction between treatment effect and hormone receptor status. In patients with hormone receptor-positive disease, HR was 1.02 (95% CI 0.63-1.63) for DFS and 1.12 (95% CI 0.59-2.11) for OS. Out of 43 patients tested for BRCA, overall incidence of POI, irrespective of treatment arm, was 20% in mBRCA patients (n = 10) and 12% in patients without mBRCA (n = 33). In mBRCA patients, incidence of POI was 0% and 33% in the CT+GnRHa and CT alone arms, respectively. One post-treatment pregnancy was described in a patient with mBRCA1 in the CT alone arm. Conclusions: The final analysis of the PROMISE-GIM6 trial at a median follow-up of 12.4 years provides reassuring evidence on the safety of GnRHa use during CT as a strategy to preserve ovarian function in premenopausal patients with hormone receptor-positive EBC. Clinical trial information: NCT00311636.

Abstract P1-15-01: Final analysis of SWOG S0230/Prevention of early menopause study (POEMS)

Abstract BACKGROUND: The SWOG S0230/POEMS study demonstrated a 70% reduction in ovarian failure (OF) with goserelin coadministration during chemotherapy (CT) for ER-negative early breast cancer (BC; Moore H et al, NEJM 2015). Goserelin use was also associated with more pregnancies as well as favorable disease free survival (DFS) and overall survival (OS). Here we report the final analysis after 5 years of follow-up. METHODS: Premenopausal women age <50 with stage I-IIIA ER/PR-negative BC to be treated with cyclophosphamide-containing CT were randomized to receive standard CT with or without monthly goserelin 3.6 mg SQ starting at least 1 week prior to the first CT dose. The primary endpoint was OF at 2-years, defined as amenorrhea for the prior 6 months and post-menopausal FSH. Secondary endpoints included pregnancies, disease free survival (DFS) and overall survival (OS). An unplanned analysis of rate of menses recovery at 2 years (presence of menses within 6 months of the 2 year time-point or pregnancy within the first 2 years) was also conducted. OF and pregnancy endpoints were analyzed using multivariable logistic regression adjusting for stratification factors (age and CT regimen); DFS and OS were examined using multivariable Cox regression, adjusting for stratification factors and stage. Two-sided p-values are reported unless otherwise specified in accordance with protocol design. RESULTS: Among 257 randomized participants, 218 were eligible and evaluable. One hundred thirty-six eligible and evaluable patients had OF data and 186 had menstrual data. Median age was 37.7 years. Among the 136 patients with OF data, the odds ratio (OR) for OF at 2 years was 0.30 (95% CI 0.1-0.98; one-sided p=0.023) comparing CT with goserelin to standard CT alone. Among 186 patients with menstrual data, 80% recovered menses by 2 years in the goserelin arm compared with 70% in the standard arm (OR=1.74, 95% CI: 0.83-3.66, p=0.15). Pregnancies, DFS and OS are reported for all 218 eligible and evaluable patients. With a median follow-up of 5.1 years, 22% of patients in the goserelin group had at least one pregnancy compared with 12% in the standard group (OR 2.38, 95% CI 1.08-5.26, p=0.03). Cumulative incidence of pregnancy at 5 years is 23% in the goserelin arm compared with 12% in the standard group. Five-year Kaplan-Meier DFS estimates are 88% in the goserelin arm compared with 79% in the standard arm (HR=0.50, p=0.05). Five-year OS is 92% with goserelin versus 83% in the standard arm (HR=0.47, p=0.06). Including all 257 randomized patients, HR for DFS and OS are 0.67 and 0.48 (p=0.18 and p=0.05). CONCLUSION: Ovarian suppression with goserelin during chemotherapy for hormone receptor-negative breast cancer reduces OF risk and, after 5 years of follow-up, continues to be associated with more pregnancies and improved survival compared with chemotherapy without goserelin. SUPPORT: NIH/NCI grant awards CA189974, CA180888, CA180819, CA074362; AstraZeneca Citation Format: Moore HCF, Unger JM, Phillips K-A, Boyle F, Hitre E, Moseley A, Porter D, Francis PA, Goldstein LJ, Gomez HL, Vallejos CS, Partridge AH, Dakhil SR, Garcia AA, Gralow J, Lombard JM, Forbes JF, Martino S, Barlow WE, Fabian CJ, Minasian L, Meyskens FL, Gelber RD, Hortobagyi GN, Albain KS. Final analysis of SWOG S0230/Prevention of early menopause study (POEMS) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-01.

Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study

ObjectiveTo assess the effect of letrozole in combination with low dose gonadotropins for ovulation induction in anovulatory infertility from polycystic ovary syndrome (PCOS) and controlled ovarian stimulation for endometriosis, and unexplained infertility patients. Study designRetrospective cohort study in a setting of private Reproductive Endocrinology and Infertility Clinic affiliated with the University. Three hundred couples (650 cycles) requiring OI/COS for PCOS (92 patients, 195 cycles), endometriosis (89 patients, 217 cycles), and unexplained infertility (119 patients, 238 cycles). Patients received 2.5mg or 5mg letrozole for 5days (D3–D7) and recombinant follicle-stimulating hormone on alternating D3-D7 and human menopausal gonadotropin-highly purified alternating D5-D10 until growth of ideally 2 mature follicles. Ovulation was triggered with 10,000 IU of HCG. Maximum number of cycles per patient was four. ResultsMain outcome measures were clinical pregnancy rates, multiple order pregnancy rates, miscarriage rates, number of follicles and endometrial thickness on the day of HCG administration. The cumulative incidence of pregnancy was estimated as 35% (95%CI: 29%–41%) overall and was highest in patients with PCOS (36.6%), followed by unexplained infertility (34.6%) and endometriosis (32.5%). The pregnancy rates per cycle in PCOS, endometriosis and unexplained infertility patients were 17%, 13.2% and 17.2% respectively, no statistically significant difference between the groups. There were three twin pregnancies in PCOS, and one in unexplained infertility group. Monofolliculogenesis was noted in 48% of patients. Conclusion(s)Letrozole-low dose gonadotropins combination appears to be effective across different causes of infertility for superovulation. The letrozole-low dose gonadotropin combination resulted in high rate of monofolliculogenesis, low occurrence of multiple gestations and no case of OHSS or cycle cancellation.

Fistula recurrence, pregnancy, and childbirth following successful closure of female genital fistula in Guinea: a longitudinal study.

SummaryBackgroundFemale genital fistula is a devastating maternal complication of delivery in developing countries. We sought to analyse the incidence and proportion of fistula recurrence, residual urinary incontinence, and pregnancy after successful fistula closure in Guinea, and describe the delivery-associated maternal and child health outcomes.MethodsWe did a longitudinal study in women discharged with a closed fistula from three repair hospitals supported by EngenderHealth in Guinea. We recruited women retrospectively (via medical record review) and prospectively at hospital discharge. We used Kaplan-Meier methods to analyse the cumulative incidence, incidence proportion, and incidence ratio of fistula recurrence, associated outcomes, and pregnancy after successful fistula closure. The primary outcome was recurrence of fistula following discharge from repair hospital in all eligible women who consented to inclusion and could provide follow-up data.Findings481 women eligible for analysis were identified retrospectively (from Jan 1, 2012, to Dec 31, 2014; 348 women) or prospectively (Jan 1 to June 20, 2015; 133 women), and followed up until June 30, 2016. Median follow-up was 28·0 months (IQR 14·6–36·6). 73 recurrent fistulas occurred, corresponding to a cumulative incidence of 71 per 1000 person-years (95% CI 56·5–89·3) and an incidence proportion of 18·4% (14·8–22·8). In 447 women who were continent at hospital discharge, we recorded 24 cases of post-repair residual urinary incontinence, equivalent to a cumulative incidence of 23·1 per 1000 person-years (14·0–36·2), and corresponding to 10·3% (5·2–19·6). In 305 women at risk of pregnancy, the cumulative incidence of pregnancy was 106·0 per 1000 person-years, corresponding to 28·4% (22·8–35·0) of these women. Of 50 women who had delivered by the time of follow-up, only nine delivered by elective caesarean section. There were 12 stillbirths, seven delivery-related fistula recurrences, and one maternal death.InterpretationRecurrence of female genital fistula and adverse pregnancy-related maternal and child health outcomes were frequent in women after fistula repair in Guinea. Interventions are needed to safeguard the health of women after fistula repair.FundingBelgian Development Cooperation (DGD), Institute of Tropical Medicine of Antwerp (ITM), and Maferinyah Training and Research Center in Rural Health (Guinea).

Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency.

Spontaneous resumption of ovarian function is not a rare phenomenon in patients with premature ovarian insufficiency (POI). The outcome of this resumption is not known. To describe the outcome following the resumption of ovarian function in POI patients. Cross-sectional study. University medical centre. Cumulative incidence of ovarian function resumption and risk factors arresting this resumption during follow-up were determined in a large cohort of POI women. Five hundred and seven patients were included in the study, with a follow-up of 3·44 ± 4·05 years (0-29). Of these, 117 (23%) had features of ovarian function resumption. The cumulative incidence of pregnancy was 3·5% among the whole cohort and 15·3% among patients with resumption of ovarian function. Fifty-five patients (47%) experienced an arrest of their resumption during the follow-up period. In univariate analysis, high FSH and DHEA levels at initial evaluation were risk factors for the arrest of the resumption of ovarian function. In multivariate analysis, high FSH levels at the initial evaluation [1·89 (1·10-3·23), P = 0·03] and older age at diagnosis [1·53 (1·01-2·33), P = 0·04] were risk factors for the arrest of this resumption. Resumption of ovarian function is not a rare or brief phenomenon in POI women. The identification of predictive factors of this resumption, as well as its duration, increases our knowledge of the natural history of POI, and will improve the medical management, especially infertility counselling of these patients.

Pregnancy Incidence in Female Nasopharyngeal Carcinoma Survivors of Reproductive Age: A Population-Based Study.

This study evaluated the pregnancy incidence in female nasopharyngeal carcinoma (NPC) survivors of reproductive age.In a nationwide cohort, 2816 female patients 15 to 50 years of age from 1998 to 2010 were identified from the Taiwan National Health Insurance Research database. Comorbidities, complications during pregnancy, and delivery status were recorded. All patients were followed up until a diagnosis of pregnancy, withdrawal from the National Health Insurance system, or December 31, 2011.Overall, 155 patients (incidence rate [IR] = 9.50) were pregnant in the NPC group, whereas 251 patients (IR = 12.80) were pregnant in the non-NPC group. The cumulative incidence of pregnancy in the NPC group was lower than that in the non-NPC group (incidence rate ratio = 0.74, 95% CI = 0.61–0.91). The adjusted hazard ratio of pregnancy in the NPC group was 0.79 with 95% CI = 0.61–0.96, compared with the non-NPC group.The incidence of pregnancy is significantly lower among female NPC survivors of reproductive age than among those without NPC.

High Incidence of Unplanned Pregnancy after Antiretroviral Therapy Initiation: Findings from a Prospective Cohort Study in South Africa

BackgroundIncreased fertility rates in HIV-infected women receiving antiretroviral therapy (ART) have been attributed to improved immunological function; it is unknown to what extent the rise in pregnancy rates is due to unintended pregnancies.MethodsNon-pregnant women ages 18–35 from four public-sector ART clinics in Johannesburg, South Africa, were enrolled into a prospective cohort and followed from August 2009–March 2011. Fertility intentions, contraception and pregnancy status were measured longitudinally at participants' routine ART clinic visits.FindingsOf the 850 women enrolled, 822 (97%) had at least one follow-up visit and contributed 745.2 person-years (PY) at-risk for incident pregnancy. Overall, 170 pregnancies were detected in 161 women (incidence rate [IR]: 21.6/100 PY [95% confidence interval (CI): 18.5–25.2]). Of the 170 pregnancies, 105 (62%) were unplanned. Unmet need for contraception was 50% higher in women initiating ART in the past year as compared to women on ART>1 year (prevalence ratio 1.5 [95% CI: 1.1–2.0]); by two years post-ART initiation, nearly one quarter of women had at least one unplanned pregnancy. Cumulative incidence of pregnancy was equally high among recent ART initiators and ART experienced participants: 23.9% [95% CI: 16.4–34.1], 15.9% [12.0–20.8], and 21.0% [16.8–26.1] for women on ART 0–1 yr, >1 yr–2 yrs, and >2 yrs respectively (log-rank, p = 0.54). Eight hormonal contraceptive failures were detected [IR: 4.4 [95% CI: 2.2–8.9], 7/8 among women using injectable methods. Overall 47% (80/170) of pregnancies were not carried to term.ConclusionsRates of unintended pregnancies among women on ART are high, including women recently initiating ART with lower CD4 counts and higher viral loads. A substantial burden of pregnancy loss was observed. Integration of contraceptive services and counselling into ART care is necessary to reduce maternal and child health risks related to mistimed and unwanted pregnancies. Further research into injectable contraceptive failures on ART is warranted.

HIV and Reproduction: Fertility, Contraception, and Preconception Issues and Interventions

HIV and Reproduction: Fertility, Contraception, and Preconception Issues and Interventions

Fertility among female hodgkin lymphoma survivors attempting pregnancy following ABVD chemotherapy

Although ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy is infrequently associated with premature amenorrhea, little is known about the success rate of women attempting pregnancy following ABVD. In the present study females treated for HL with ABVD chemotherapy without pelvic radiation therapy (RT) and who were alive without relapse > or =3 years after treatment were identified from a clinical database and screened for inclusion. Using a standardized questionnaire, we determined the pregnancy rate (i.e. time-to-pregnancy, TTP) among survivors who had become pregnant, tried to become pregnant, or who had been sexually active for over 2 months without using contraception at any time following ABVD. The cumulative incidence of pregnancy was calculated using the Kaplan-Meier method. Cox proportional hazards models were constructed to compare the pregnancy rate among HL survivors to that reported by friend or sibling controls. Thirty-six female HL survivors, who had attempted pregnancy after ABVD treatment, and 29 controls, completed the survey. Eighteen patients (50%) received 2-4 cycles of ABVD, 16 (44%) received 4-6 cycles, and 2 (6%) received >6 cycles. The median TTP among both HL survivors and controls was 2.0 months. The 12-month pregnancy rates were 70% and 75%, respectively. The fertility ratio (FR) for HL survivors versus controls was 0.94 (95%CI = 0.53-1.66; p = 0.84) after adjusting for age and frequency of intercourse (where FR < 1 indicates subfertility). Age at treatment and the number of cycles of chemotherapy were not associated with pregnancy rate among HL survivors. Female HL patients who had survived without recurrence > or =3 years and who had attempted pregnancy after ABVD did not experience significant sub-fertility.

Brucellosis in pregnant women.

Brucella species occasionally cause spontaneous human abortion, but theories regarding whether they do so more frequently than do other infectious pathogens remain controversial. We reviewed 92 pregnant women who presented with acute brucellosis at a Saudi Arabian hospital. From 1983 through 1995, the cumulative incidence of pregnancy and brucellosis was 1.3 cases per 1000 delivered obstetrical discharges. The incidence of spontaneous abortion in the first and second trimesters was 43%, and the incidence of intrauterine fetal death in the third trimester was 2%. Antepartum antimicrobial therapy with cotrimoxazole or cotrimoxazole/rifampin was protective against spontaneous abortion (relative risk, 0.14; 95% confidence interval, 0.06--0.37; P<.0001). The beneficial effect of treatment occurred in women with febrile illness; vaginal bleeding at presentation usually led to spontaneous abortion. This study demonstrated that the incidence of spontaneous abortion among pregnant women with brucellosis is high and that these women should receive prompt therapy with antimicrobial agents when they present for medical care.

Incidence and consequences of pregnancy in women with known duration of HIV infection. Italian Seroconversion Study Group

The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease. To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women. All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years. A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24). Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.

Incidence and Consequences of Pregnancy in Women With Known Duration of HIV Infection

The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease.To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women.All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years.A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24).Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.

Dose-response relationship between dose of clomiphene citrate and incidence of ovulation.

AbstractOne hundred and fifty anovulatory, infertile women were treated with clomiphene citrate in an individualized, graduated therapeutic regimen. Women with high serum follicle stimulating hormone or prolactin concentrations were not included. Ovulation was induced in 135 (90.0%) of the 150 women. Of the 55 women who achieved pregnancy, 50 (90.9%) did so at a dose of 150 mg for 5 days or less. Five pregnancies (9.1%) were achieved with higher doses. There was a significant correlation between the total dose of clomiphene citrate administered per cycle and the cumulative incidence of ovulation. There was also a significant relationship between the total dose of clomiphene per cycle and the cumulative incidence of pregnancy.