Mode of conception in relation to nausea and vomiting of pregnancy: a nested matched cohort study in Sweden.

Nausea and vomiting of pregnancy (NVP) is a common condition reported however inconclusively among pregnancies after assisted conception. The study objective was thus to explore whether NVP is associated to mode of conception or other in vitro fertilization (IVF)-related variables. This nested matched cohort study, originating from the BASIC-project, was conducted at the Uppsala University Hospital in Sweden between 2010 and 2016. IVF pregnancies (n = 210) and age and parity-matched women with spontaneous pregnancies (n = 420) comprised the study sample. The study outcome was self-reported NVP at gestational week 17. IVF treatment and pregnancy data were obtained after scrutinization of the medical records. NVP with or without medications was not associated with mode of conception (chi-square test, p = 0.889), even after adjusting for potential confounders. In a subgroup analysis among IVF pregnancies, NVP without medication was more frequently seen in the group who received cleavage stage embryos vs blastocysts (chi-square test, p = 0.019), exhibiting a marginally significant but strongly increased effect even after adjustment [crude RRR 3.82 (95% CI 1.23-11.92) and adjusted RRR 3.42 (95% CI 0.96-12.11)]. No difference in the rate of NVP with or without medication between women that underwent fresh and frozen/thawed embryo transfers as well as IVF or ICSI was observed. Conception through IVF is not associated with NVP. Transfer of a blastocyst may decrease the risk of developing NVP and further, large-scale prospective studies are required to validate this finding.

Early initiation of anti-androgen treatment is associated with increased probability of spontaneous conception leading to childbirth in women with polycystic ovary syndrome: a population-based multiregistry cohort study in Sweden.

STUDY QUESTION: Is anti-androgen treatment during adolescence associated with an improved probability of spontaneous conception leading to childbirth in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Early initiation of anti-androgen treatment is associated with an increased probability of childbirth after spontaneous conception among women with PCOS. WHAT IS KNOWN ALREADY: PCOS is the most common endocrinopathy affecting women of reproductive age. Hyperandrogenism and menstrual irregularities associated with PCOS typically emerge in early adolescence. Previous work indicates that diagnosis at an earlier age (<25 years) is associated with higher fecundity compared to a later diagnosis. STUDY DESIGN, SIZE, DURATION: This population-based study utilized five linked Swedish national registries. A total of 15 106 women with PCOS and 73 786 control women were included. Women were followed from when they turned 18 years of age until the end of 2015, leading to a maximum follow-up of 10 years. First childbirth after spontaneous conception was the main outcome, as identified from the Medical Birth Registry. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants included all women born between 1987 and 1996 with a diagnosis of PCOS in the Swedish Patient Registry and randomly selected non-PCOS controls (ratio 1:5). Information on anti-androgenic treatment was retrieved from the Swedish Prescribed Drug Registry with the use of Anatomic Therapeutic Chemical (ATC) codes. Women with PCOS who were not treated with any anti-androgenic medication were regarded as normo-androgenic, while those treated were regarded as hyperandrogenic. Women were further classified as being mildly hyperandrogenic if they received anti-androgenic combined oral contraceptive (aaCOC) monotherapy, or severely hyperandrogenic if they received other anti-androgens with or without aaCOCs. Early and late users comprised women with PCOS who started anti-androgenic treatment initiated either during adolescence (≤ 18 years of age) or after adolescence (>18 years), respectively. The probability of first childbirth after spontaneous conception was analyzed with the use of Kaplan-Meier hazard curve. The fecundity rate (FR) and 95% confidence interval for the time to first childbirth that were conceived spontaneously were calculated using Cox proportional hazards regression models, with adjustment for obesity, birth year, country of birth and education level. MAIN RESULTS AND THE ROLE OF CHANCE: The probability of childbirth after spontaneous conception in the PCOS group compared to non-PCOS controls was 11% lower among normo-androgenic (adjusted FR 0.68 (95% CI 0.64-0.72)), and 40% lower among hyperandrogenic women with PCOS (adjusted FR 0.53 (95% CI 0.50-0.57)). FR was lowest among severely hyperandrogenic women with PCOS compared to normo-androgenic women with PCOS (adjusted FR 0.60 (95% CI 0.52-0.69)), followed by mildly hyperandrogenic women with PCOS (adjusted FR 0.84 (95% CI 0.77-0.93)). Compared to early anti-androgenic treatment users, late users exhibited a lower probability of childbirth after spontaneous conception (adjusted FR 0.79 (95% CI 0.68-0.92)). LIMITATIONS, REASONS FOR CAUTION: We lacked direct information on the intention to conceive and the androgenic biochemical status of the PCOS participants, applying instead the use of anti-androgenic medications as a proxy of hyperandrogenism. The duration of anti-androgenic treatment utilized is not known, only the age at prescription. Results are not adjusted for BMI, but for obesity diagnosis. The period of follow-up (10 years) was restricted by the need to include only those women for whom data were available on the dispensing of medications during adolescence (born between 1987 and 1996). Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Early initiation of anti-androgen treatment is associated with better spontaneous fertility rate. These findings support the need for future interventional randomized prospective studies investigating critical windows of anti-androgen treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Health Research Council of New Zealand (18-671), the Swedish Society of Medicine and the Uppsala University Hospital. Evangelia Elenis has, over the past year, received lecture fee from Gedeon Richter outside the submitted work. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

SSRI use during pregnancy and risk for postpartum haemorrhage: a national register-based cohort study in Sweden.

OBJECTIVE: Evaluate whether selective serotonin reuptake inhibitor (SSRI) use during pregnancy, as well as prior or current untreated psychiatric illness is associated with postpartum haemorrhage (PPH). DESIGN: National register-based cohort study based on data from the Swedish Pregnancy Register. SETTING: Sweden, nationwide coverage. POPULATION: A total of 31 159 pregnant women with singleton deliveries after gestational week 22+0 between January 2013 and July 2017. METHODS: Pregnant women with self-reported SSRI use at any time point during pregnancy were compared with non-SSRI-treated women with prior or current psychiatric illness, as well as wiith healthy women with no psychiatric illness or reporting SSRI use. MAIN OUTCOME MEASURES: Postpartum haemorrhage defined as blood loss >1000 ml during the first 2 hours postpartum reported by the delivering midwife or obstetrician. RESULTS: Postpartum haemorrhage prevalence was 7.0% among healthy women, 7.6% among women with prior or current psychiatric illness and 9.1% among women treated with SSRI. The unadjusted odds for PPH among women with prior or current psychiatric illness and women on SSRI treatment were increased by 9 and 34%, respectively, compared with healthy unmedicated women without a history of psychiatric illness (odds ratio [OR] 1.09, 95% CI 1.04-1.14 and OR 1.34, 95% CI 1.24-1.44, respectively). The estimates remained unchanged after adjustment for several confounders (such as maternal age, body mass index [BMI], parity, prior caesarean section, smoking, occupation and country of birth) and potential covariates (such as delivery mode, polyhydramnion, preterm delivery, labour dystocia and infant birthweight >4000 g). CONCLUSIONS: Higher risk for PPH was observed both among women treated with SSRI during pregnancy and among women with prior or current psychiatric illness. TWEETABLE ABSTRACT: SSRI use at any point during pregnancy and prior or current history of psychiatric illness was associated with an increased likelihood for PPH.

Fecundity among women with polycystic ovary syndrome (PCOS)-a population-based study.

STUDY QUESTION: Does the long-term fecundity of women with polycystic ovary syndrome (PCOS) differ from those without PCOS? SUMMARY ANSWER: Cumulative probability of childbirth is similar between women with and without PCOS. WHAT IS KNOWN ALREADY: PCOS is the main cause of anovulatory infertility in women after menarche. Previous studies indirectly suggest that fecundity in women with PCOS over the longer term may not be lower than in women without PCOS. STUDY DESIGN, SIZE, DURATION: This is a population-based study using four linked Swedish national registries. A total of 45 395 women with PCOS and 217 049 non-PCOS women were included. Follow-up began at the age of 18 years and continued for a maximum of 26 years, from 1989 to the end of 2015. Childbirth was the main outcome, as identified from the Medical Birth Register. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women born between 1971 and 1997 who were identified with a PCOS diagnosis in the Swedish Patient Registry between 1 January 2001 and 31 December 2016 were included in the study population. Five controls per women with PCOS were randomly drawn from the Total Population Registry. The control women were born in the same year and living in the same municipality as the patient. The fecundity ratio (FR) was calculated by clustered Cox regression using a robust variance, adjusted for maternal birth period, country of birth and level of education. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative probability of childbirth was 80.2% (95% CI, 79.5-80.9%) in women with PCOS and 78.2% (95% CI, 77.9-78.5%) in those without PCOS. Adjusted FR was 0.81 (95% CI, 0.80-0.82) for first childbirth and 0.58 (95% CI, 0.57-0.60) for first childbirth following a spontaneous pregnancy. The FR for second childbirth was 0.79 (95% CI, 0.77-0.80). Women with PCOS had more than one child less frequently than the comparison group. Within the PCOS group, early age at diagnosis, later birth year, Nordic country of origin and low educational level positively influenced the FR. LIMITATIONS, REASONS FOR CAUTION: Results are not adjusted for BMI, and time from intention to conceive to first childbirth could not be captured. Data on pregnancies, miscarriages or abortions and fertility treatment are unknown for women who did not give birth during the study period. Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes. WIDER IMPLICATIONS OF THE FINDINGS: While cumulative probability of childbirth is similar between groups, women with PCOS need longer time to achieve their first childbirth. Women with PCOS have a lower FR and give birth to fewer children per woman than women without PCOS. Early diagnosis of and information about PCOS may improve affected women's reproductive potential. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Swedish Society of Medicine. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests.

Sexual orientation of women does not affect outcome of fertility treatment with donated sperm.

STUDY QUESTION: Is there a difference in fertility between heterosexual women and lesbians undergoing sperm donation? SUMMARY ANSWER: Women undergoing treatment with donated sperm are equally fertile regardless of sexual orientation. WHAT IS KNOWN ALREADY: Lesbians have an increased prevalence of smoking, obesity, sexually transmitted diseases and, possibly, polycystic ovary syndrome, all factors known to affect fertility. Previous studies on sperm donation inseminations (D-IUI) show conflicting results regarding pregnancy outcome. STUDY DESIGN, SIZE, DURATION: This is a national study of 171 lesbians and 124 heterosexual women undergoing sperm donation both as D-IUI (lesbian n = 438, heterosexual n = 298) and as embryo transfers (ET) after IVF with donated sperm (lesbians n = 225, heterosexuals n = 230) during 2005-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: All clinics in Sweden offering sperm donation recruited patients. Differences in patients' medical history, treatment results and number of treatments to live birth were analyzed using independent samples t-test, Pearson's χ(2) test or Fisher's exact probability test. MAIN RESULTS AND THE ROLE OF CHANCE: 71.8% of heterosexuals and 69.0% of lesbians had a child after treatment. The mean number of treatments was 4.2 for heterosexual women and 3.9 for lesbians. The total live birth rate, regardless of treatment type, was 19.7% for heterosexuals and 19.5% for lesbians. For D-IUI, the live birth rate was 12.8% for heterosexuals and 16.0% for lesbians and the live birth rate for all IVF embryo transfers (fresh and thawed cycles) was 28.7% for heterosexuals and 26.2% for lesbians. There were no differences in live birth rate between the groups for each of the different types of insemination stimulations (natural cycle; clomiphene citrate; FSH; clomiphene citrate and FSH combined). Nor was there a difference in live birth rate between the groups for either fresh or thawed embryo transfer. There was no difference between the proportions of women in either group or the number of treatments needed to achieve a live birth. Heterosexuals had a higher prevalence of smokers (9.2%), uterine polyps (7.2%) or previous children (11.3%) than lesbians (smokers 2.8%, P = 0.03; polyps 1.8%, P = 0.03; child 2.5%, P = 0.003). LIMITATIONS, REASONS FOR CAUTION: This study is limited to women living in stable relationships undergoing treatment with donated sperm in a clinical setting and may not apply to single women or those undergoing home inseminations. WIDER IMPLICATIONS OF THE FINDINGS: These results may influence healthcare policy decisions as well as increase the quality of clinical care and medical knowledge of healthcare professionals. The data also have important implications for individuals regarding screening, infertility diagnostic procedures and treatment types offered to heterosexuals and lesbians seeking pregnancy through sperm donation. STUDY FUNDING/COMPETING INTEREST(S): Funding was granted by the Stiftelsen Familjeplaneringsfonden i Uppsala; the Swedish Research Council for Health, Working Life and Welfare; and the Marianne and Marcus Wallenberg Foundation. The authors report no conflicts of interest.