Anxiety and depression in expectant parents: ART versus spontaneous conception.

STUDY QUESTION: Do expectant parents experience increased anxiety and depression during pregnancies conceived through ART compared to spontaneous conception? SUMMARY ANSWER: Among all expectant parents in the sample, those who conceived through ART reported overall lower levels of anxiety and depression in pregnancy compared to expectant parents who conceived spontaneously, while in the subsample of parents who conceived both through ART and spontaneous conception, expectant mothers experienced increased anxiety and depression in early pregnancy following ART compared to spontaneous conception. WHAT IS KNOWN ALREADY: Previous research on expectant parents' psychosocial adjustment in response to ART has found mixed results, with some studies suggesting ART is associated with increased anxiety and depression, and other studies suggesting improved mental health or no relationship. Mixed findings may relate to the use of cross-sectional designs that do not account for confounding differences between groups, or variability in the timing of assessment. STUDY DESIGN, SIZE, DURATION: This prospective cohort study used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), which includes 2960 pregnant women who underwent ART and 108 183 women who conceived spontaneously. Of these, a subsample of expectant parents had two consecutive pregnancies with one pregnancy resulting from ART and one conceived spontaneously (n = 286 women, n = 211 partners). Women self-reported their composite symptoms of anxiety and depression at two timepoints during each pregnancy (gestational weeks 17 and 30). Their partners self-reported composite symptoms of anxiety and depression at 17 weeks gestation during each pregnancy. Couples reported their relationship satisfaction at 17 weeks gestation. MAIN RESULTS AND THE ROLE OF CHANGE: Using a conventional full-cohort analysis we found that ART was associated with less total anxiety and depression and greater relationship satisfaction, compared to spontaneous conception among both women and men. However, in the subsample of parents who experienced both ART and spontaneous pregnancies, ART was associated with increased levels of maternal anxiety and depression at gestational age 17 weeks (M = 1.19), compared to spontaneous pregnancies (M = 1.15), 95% CI of the mean difference 0.006, 0.074. At 30 weeks gestation, anxiety and depression were similar across both types of pregnancies. Expectant fathers reported similar levels of anxiety and depression at 17 weeks gestation during both pregnancies. Among women relationship satisfaction was higher following ART conception than spontaneous conception. LIMITATIONS, REASONS FOR CAUTION: There is potential for selection effects in the sample, as women who have conceived through both ART and spontaneous conception in their first two pregnancies are rare. In addition, several factors that may be important predictors of mental health in this context, such as previous miscarriages and long-term infertility, were not assessed in the current study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings indicate that previous discrepancies in the literature may be related to inherent differences between the groups of parents receiving reproductive treatment and those who do not. This study addresses that limitation by prospectively comparing different types of pregnancies within the same expectant parents. Earlier inconsistencies may also relate to variations in gestational age when anxiety and depression were assessed. By examining symptoms at two timepoints in each pregnancy, we were able to examine the relation between gestational age and symptoms of anxiety and depression. STUDY FUNDING/COMPETING INTEREST(S): The MoBa is supported by the Norwegian Ministry of Health and the Norwegian Research Council/FUGE (grant number 151918/S10). This work was also supported by the Research Council of Norway grant number 288083 and 301004. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Can time to menopause be predicted?

Menopause represents the definite end of a woman's reproductive life and the onset of a persistent hypoestrogenic state. This postmenopausal period will for most women last several decades. Although mean menopausal age seems to have increased somewhat during the last century, there is a significant individual variation in age at natural menopause. With efficient contraception, women of reproductive age can now, to some extent, choose when they want to have children. As a consequence of this and other sociodemographic changes, age at first birth has increased significantly over the last 50 years. It is well documented that long before a woman enters the menopausal transition and subsequent menopause, fertility declines and finally ceases. Being able to predict when a woman will enter menopause would therefore, from a reproductive perspective, be of major interest. Several sociodemographic, morphometric, and endocrine factors are associated with age at menopause or time to menopause. Unfortunately the sensitivity and specificity of these in predicting time to or age at menopause are low. Therefore, with the exception of anti-Müllerian hormone measurements, either alone or in combination with chronological age close to menopause, there are as of now no reliable ways of predicting when a woman will enter menopause.

Risk of cardiovascular disease after preventive salpingo-oophorectomy.

INTRODUCTION: Breast cancer susceptibility gene (BRCA) mutation carriers are recommended to undergo early oophorectomy to prevent ovarian cancer. Premature loss of ovarian hormones may increase the risk of cardiovascular disease. Because women with preventive oophorectomy are mainly young and healthy, they rarely undergo specialized cardiological surveillance. We compared the risk of cardiovascular disease in women after preventive oophorectomy with reference women. METHODS: In an historical cohort study, we included 134 women aged ≤52 years after preventive oophorectomy and 268 age matched premenopausal reference women, aged 52 years or less, from the general population, excluding participants with diabetes or cardiovascular disease. The Norwegian risk assessment tool (NORRISK 2) was used to estimate 10 year cardiovascular risk. This algorithm was validated in a large Norwegian population and is based on age, smoking, systolic blood pressure, total and high density lipoprotein cholesterol, antihypertensive medication, and family history of cardiovascular disease. We also examined cardiometabolic factors (levels of triglycerides and high sensitivity C reactive protein, as well as body mass index and waist circumference) not included in the NORRISK 2 calculation. RESULTS: Median age in the preventive oophorectomy and reference groups were 47 (range 33-52) and 46 (31-52) years, respectively. Mean time since surgery in the preventive oophorectomy group was 4.2 years (standard deviation (SD) 2.8). Ten year cardiovascular risk was similar in women after preventive oophorectomy and reference women (mean 1.15% (SD 1.00) vs 1.25 (1.09), respectively, p=0.4). Women in the preventive oophorectomy group had a lower body mass index (24.7 kg/m2 (4.0) vs 26.2 (4.8), p=0.003) and waist circumference (86 cm vs 89, p=0.006). The overall cardiovascular risk estimation was comparable among hormone therapy users and non-users, but hormone therapy users had lower total cholesterol and waist circumference. DISCUSSION: Women who underwent preventive oophorectomy had a similar risk of cardiovascular disease as population based reference women, estimated according to risk factors easily measured in general practice. Cardiometabolic risks were not increased in the preventive oophorectomy group.

Development of a prediction model to aid primary care physicians in early identification of women at high risk of developing endometriosis: cross-sectional study.

OBJECTIVES: To identify predictors of disease among a few factors commonly associated with endometriosis and if successful, to combine these to develop a prediction model to aid primary care physicians in early identification of women at high risk of developing endometriosis. DESIGN: Cross-sectional anonymous postal questionnaire study. SETTING: Women aged 18-45 years recruited from the Norwegian Endometriosis Association and a random sample of women residing in Oslo, Norway. PARTICIPANTS: 157 women with and 156 women without endometriosis. MAIN OUTCOME MEASURES: Logistic and least absolute shrinkage and selection operator (LASSO) regression analyses were performed with endometriosis as dependent variable. Predictors were identified and combined to develop a prediction model. The predictive ability of the model was evaluated by calculating the area under the receiver operating characteristic curve (AUC) and positive predictive values (PPVs) and negative predictive values (NPVs). To take into account the likelihood of skewed representativeness of the patient sample towards high symptom burden, we considered the hypothetical prevalences of endometriosis in the general population 0.1%, 0.5%, 1% and 2%. RESULTS: The predictors absenteeism from school due to dysmenorrhea and family history of endometriosis demonstrated the strongest association with disease. The model based on logistic regression (AUC 0.83) included these two predictors only, while the model based on LASSO regression (AUC 0.85) included two more: severe dysmenorrhea in adolescence and use of painkillers due to dysmenorrhea in adolescence. For the prevalences 0.1%, 0.5%, 1% and 2%, both models ascertained endometriosis with PPV equal to 2.0%, 9.4%, 17.2% and 29.6%, respectively. NPV was at least 98% for all values considered. CONCLUSIONS: External validation is needed before model implementation. Meanwhile, endometriosis should be considered a differential diagnosis in women with frequent absenteeism from school or work due to painful menstruations and positive family history of endometriosis.

Childbirth close to natural menopause: does age at menopause matter?

RESEARCH QUESTION: Does a successful spontaneous pregnancy in the years close to natural menopause depend on age at menopause? DESIGN: This was a retrospective population-based study of 4157 parous postmenopausal women in Norway, born during the years 1925-1940. Data were obtained by two self-administered questionnaires in the HUNT2 Survey (1995-1997). We calculated the proportions of women who gave birth within 5 years and within 10 years prior to menopause both among all women, and according to categories of age at menopause. RESULTS: Overall, 2.7% (114/4157) of all women gave birth within 5 years, and 11.7% (487/4157) gave birth within 10 years, prior to menopause. Among women with menopause before the age of 45 years, 23.5% (81/344) gave birth within 5 years, and 55.5% (191/344) gave birth within 10 years, before menopause. Among the women with menopause at the age of 55 years or older, no women (0/474) gave birth within 5 years, and 0.2% (1/474) gave birth within 10 years, prior to menopause. CONCLUSIONS: More than half of the women with menopause before the age of 45 years gave birth within the 10 years before natural menopause, whereas virtually no women with menopause at the age of 55 years or older did. Thus, the length of the sterile interval before natural menopause may vary by age at menopause.

Cervical microbiota in women with cervical intra-epithelial neoplasia, prior to and after local excisional treatment, a Norwegian cohort study.

BACKGROUND: Local treatment for cervical intraepithelial neoplasia (CIN) by Loop Electrosurgical Excision Procedure (LEEP) has been correlated with reproductive morbidity, while the cervicovaginal microbiota is also known to affect the risk of preterm delivery. CIN and treatment by LEEP might change the cervical microbiota. The main aim of this study was to describe the cervical microbiota before and after LEEP and assess its associaton with cone depth and HPV persistence. Further, we aimed to compare the microbiota to references with normal cervical cytology. METHODS: Between 2005 and 2007, we prospectively identified 89 women planned for LEEP in a Norwegian hospital and recruited 100 references with a normal cervical cytology. Endocervical swabs were collected prior to treatment and at six (n = 77) and 12 months (n = 72) post LEEP for bacterial culture and PCR, and post LEEP for DNA testing for human papillomavirus (HPV). We compared the cervical microbiota composition before and after treatment and between women planned for LEEP vs references. RESULTS: There was a reduction in the number of non-Lactobacillus bacterial species six and 12 months after LEEP compared to before treatment and a tendency towards a concomitant increase in Lactobacillus. No association between the detection of cervical bacteria, HPV persistence or cone depth was found. Women planned for LEEP carried significantly more Bacteroides spp., Gardnerella vaginalis, Mycoplasma hominis and Ureaplasma parvum as well as a greater number of bacterial species than the references. CONCLUSIONS: Local excisional treatment appears to alter the cervical microbiota towards a less diverse microbiota. Women with CIN have a more diverse cervical microbiota compared to women with normal cervical cytology.

Lack of cross-cultural validity of the Endometriosis Health Profile-30.

INTRODUCTION: The Endometriosis Health Profile-30 is a disease-specific patient-reported outcome measure of health-related quality of life. Cross-cultural validation of the Endometriosis Health Profile-30 has been performed for several translated versions. The aim of this study was to evaluate the measurement properties of a Norwegian version Endometriosis Health Profile-30. METHODS: This study was designed as a cross-sectional anonymous postal questionnaire study. A total of 157 women with endometriosis were included during a period from 2012 to 2013. Women aged 18-45 years were recruited from the Norwegian Endometriosis Association. Principal components analysis with varimax rotation was used to assess construct validity. Short Form-36 was used to determine convergent validity. Cronbach's alpha was used to measure internal consistency. Intraclass correlation coefficients and paired t-tests were used to evaluate test-retest reliability. Floor and ceiling effects were estimated. RESULTS: Factor analysis resulted in a three and five-factor model for the core and modular questionnaire, respectively. Factor analysis could not support construct validity of the scales self-image and treatment. The Norwegian version Endometriosis Health Profile-30 demonstrated acceptable internal consistency and test-retest reliability, except for the scale relationship with children. Floor effects were observed for the scales self-image (20.1%), work life (33.9%), relationship with children (34.2%), and medical profession (20.5%). CONCLUSION: The construct self-image does not seem to be measured appropriately by the Norwegian version Endometriosis Health Profile-30, suggesting a lack of cross-cultural validity of the Endometriosis Health Profile-30. With multinational studies increasing, adequate translation, cross-cultural adaptation, and cross-cultural validation of instruments are essential to ensure equivalence in languages and cultures other than the original.

Health-related quality of life in women with endometriosis, compared with the general population and women with rheumatoid arthritis.

INTRODUCTION: Women with endometriosis have reduced health-related quality of life (HRQoL). However, comparisons to the general population and other patient groups are lacking. MATERIAL AND METHODS: The present cross-sectional questionnaire study included 157 women with endometriosis, 156 women from the general population, and 837 women with rheumatoid arthritis (RA). During a period from 2012 to 2013, women aged 18-45 years were recruited from the Norwegian Endometriosis Association and from a random sample of women residing in Oslo, Norway. HRQoL data from women with RA were included from a survey conducted in 2009 among patients of the Oslo Rheumatoid Arthritis Register. The Short Form-36 (SF-36) questionnaire was used to measure HRQoL. RESULTS: Compared with the control group, the endometriosis group had significantly reduced mean scores for all SF-36 scales. The difference was largest for the scale bodily pain with a mean score of 47.6 in the endometriosis group vs 81.5 in the control group. Compared with the RA group, the endometriosis group had significantly reduced mean scores for the three SF-36 scales vitality, social functioning, and mental health. The mean scores of these scales in the endometriosis group were 33.4, 62.7, and 66.3, respectively, vs 42.7, 68.8, and 72.6 in the RA group. CONCLUSIONS: Women with moderate to severe endometriosis seem to have overall impaired HRQoL compared with women from the general population, and poorer mental HRQoL compared with women with RA.

Fertility after cryopreservation of ovarian tissue due to cancer treatment. / Fertilitet etter kryopreservering av ovarialvev ved kreftbehandling.

BAKGRUNN: Kryopreservering av ovarialvev som fertilitetsbevarende metode tilbys prepubertale jenter og kvinner i reproduktiv alder med høy risiko for å utvikle prematur ovarialsvikt i forbindelse med medisinsk eller kirurgisk behandling. I denne studien ønsket vi å kartlegge fertilitet og prematur ovarialsvikt hos kvinner som har fått gjort kryopreservering av ovarialvev i forbindelse med kreftbehandling. MATERIALE OG METODE: Et spørreskjema ble i 2014 sendt til 94 kvinner over 18 år som i perioden 2004-12 hadde fått kryopreservert ovarialvev i forbindelse med behandling for en malign tilstand. Skjemaet inneholdt spørsmål om menstruasjonsfrekvens, prevensjonsbruk, fertilitet, fremtidig barneønske og sannsynlighet for at de ville benytte ovarialvevet senere. Av de 77 kvinnene som returnerte spørreskjemaet, ble 74 kvinner inkludert i studien. RESULTATER: Totalt 20 av 74 kvinner (27 %) hadde prematur ovarialsvikt definert som opphør av ovarialfunksjonen før 40 års alder. Risikoen var lavest hos kvinner behandlet for brystkreft (5 %) og høyest hos kvinner behandlet for leukemi (75 %). Størst risiko for prematur ovarialsvikt fant man i pasientgruppene som hadde gjennomgått stamcelletransplantasjon, strålebehandling mot helkropp og/eller abdomen og bekken. Til sammen hadde 22 kvinner født 31 barn etter kreftbehandlingen, hvorav to etter reimplantasjon av ovarialvev. FORTOLKNING: Risikoen for å utvikle prematur ovarialsvikt er avhengig av pasientens kreftdiagnose. Hvilke fertilitetsbevarende tiltak som anbefales, bør differensieres avhengig av pasienten kreftdiagnose og planlagt behandling.

Ovulation induction in polycystic ovary syndrome.

The objective of this narrative review was to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight women with PCOS the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without adverse effects in the doses recommended, may be suggested. Additional first-line medical alternatives include insulin sensitizers, selective estrogen receptor modulators, and aromatase inhibitors. Of these, the aromatase inhibitor letrozole and the combination of clomiphene citrate and metformin have the highest rates of ovulation and live birth. Second-line treatments are ovarian electrocautery and low-dose follicle-stimulating hormone stimulation. Controlled ovarian stimulation with in vitro fertilization, should be considered the last option as it carries a significant risk of ovarian hyperstimulation syndrome in patients with PCOS.

Maternal concentrations of human chorionic gonadotrophin in very early IVF pregnancies and duration of pregnancy: a follow-up study.

RESEARCH QUESTION: Are maternal concentrations of human chorionic gonadotropin (HCG) on a fixed day after embryo transfer associated with duration of pregnancy? DESIGN: A follow-up study of 1917 singleton pregnancies after IVF was performed. Embryos were cultured for 2 days and maternal HCG concentration quantified on day 12 after embryo transfer. Duration of pregnancy was obtained from the Medical Birth Registry of Norway. Association of HCG concentration (log2-transformed) with duration of pregnancy was estimated as hazard ratios (HR) with 95% confidence intervals (CI) by applying Cox regression proportional hazard models, where time to delivery for pregnancies shortened because of planned Caesarean delivery or induction of labour was treated as censored. RESULTS: The estimated median duration of pregnancy from embryo transfer was 266 days (95% CI 266-267 days). Maternal concentration of HCG on day 12 after embryo transfer varied from 1 to 588 IU/l (median 117 IU/l). Duration of pregnancy decreased by increasing HCG concentration, significantly in pregnancies delivered at full term ((257-270 days after embryo transfer; HR 1.127, 95% CI 1.026-1.238, P = 0.012). For each doubling of HCG concentration on day 12 after embryo transfer, duration of pregnancy was shortened by 0.51 days. Adjustment for maternal age, prepregnancy body mass index, being a first-time mother and number of embryos transferred did not change the association. CONCLUSION: High maternal HCG concentration on a fixed day after embryo transfer is likely to indicate early embryo implantation. After embryo transfer, pregnancies with early implantation are shorter than pregnancies with late implantation.

Maternal human chorionic gonadotrophin concentrations in very early pregnancy and risk of hyperemesis gravidarum: A retrospective cohort study of 4372 pregnancies after in vitro fertilization.

OBJECTIVE: We investigated the association of human chorionic gonadotrophin (hCG) concentrations on a fixed day in very early pregnancy with development of hyperemesis gravidarum. STUDY DESIGN: This retrospective cohort study included 3107 singleton and 1265 twin pregnancies after in vitro fertilization treated at Department of Reproductive Medicine, Rikshospitalet, Oslo University Hospital, Norway in the period 1996-2013. Maternal serum hCG concentrations was measured on day 12 after embryo transfer. Information about development of hyperemesis gravidarum was obtained by individual linkage to the Medical Birth Registry of Norway. We studied hCG concentrations in very early pregnancy according to development of hyperemesis gravidarum, in singleton and twin pregnancies separately. We estimated the odds ratios for hyperemesis gravidarum with 95% confidence intervals according to quartiles of hCG concentrations. RESULTS: In twin pregnancies as compared to singleton pregnancies, we found higher mean maternal hCG concentrations (219 IU/L versus 130 IU/L, p<0.001 Student's t-test) and higher prevalence of hyperemesis gravidarum (2.7% versus 1.4%, p=0.002 chi-squared test). However, both in singleton and in twin pregnancies, we found no significant difference in mean hCG concentrations between women who developed hyperemesis gravidarum and women who did not (Singletons: 122 IU/L versus 130 IU/L, p=0.504. Twins: 234 IU/L versus 219 IU/L, p=0.417 Student's t-test). We found no significant differences in odds ratios for developing hyperemesis gravidarum according to quartiles of hCG concentrations. CONCLUSIONS: We found no association of maternal hCG concentrations on a fixed day in early pregnancy with development of hyperemesis gravidarum.

Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options.

Endometriosis is a common condition in women of reproductive age. In addition to pain, endometriosis may also reduce fertility. The causes of infertility in women with endometriosis may range from anatomical distortions due to adhesions and fibrosis to endocrine abnormalities and immunological disturbances. In some cases, the various pathophysiological disturbances seem to interact through mechanisms so far not fully understood. Whether surgery should be offered as a treatment option in endometriosis-associated infertility has become controversial, partly due to its modest or undocumented effect. Medical or hormonal treatment alone has little or no effect and should only be used in conjunction with assisted reproductive technology (ART). Of the various methods of ART, intrauterine insemination, due to its simplicity, can be recommended in women with minimal or mild peritoneal endometriosis, even though insemination may yield a lower success rate than in women without endometriosis. In vitro fertilization (IVF) is an effective treatment option in less-advanced disease stages, and the success rates are similar to the results in other causes of infertility. However, women with more advanced stages of endometriosis have lower success rates with IVF.

Elective cesarean section or not? Maternal age and risk of adverse outcomes at term: a population-based registry study of low-risk primiparous women.

BACKGROUND: Maternal age at delivery and cesarean section rates are increasing. In older women, the decision on delivery mode may be influenced by a reported increased risk of surgical interventions during labor and complications with increasing maternal age. We examined the association between maternal age and adverse outcomes in low-risk primiparous women, and the risk of adverse outcomes by delivery modes, both planned and performed (elective and emergency cesarean section, operative vaginal delivery, and unassisted vaginal delivery) in women aged ≥ 35 years. METHODS: A population-based registry study was conducted using data from the Medical Birth Registry of Norway and Statistics Norway including 169,583 low-risk primiparas with singleton, cephalic labors at ≥ 37 weeks during 1999 - 2009. Outcomes studied were obstetric blood loss, maternal transfer to intensive care units, 5-min Apgar score, and neonatal complications. We adjusted for potential confounders using relative risk models and multinomial logistic regression. RESULTS: Most adverse outcomes increased with increasing maternal age. However, the increase in absolute risks was low, except for moderate obstetric blood loss and transfer to the neonatal intensive care unit (NICU). Operative deliveries increased with increasing maternal age and in women aged ≥ 35 years, the risk of maternal complications in operative delivery increased. Neonatal adverse outcomes increased mainly in emergency operative deliveries. Moderate blood loss was three times more likely in elective and emergency cesarean section than in unassisted vaginal delivery, and twice as likely in operative vaginal delivery. Low Apgar score and neonatal complications occurred two to three times more often in emergency operative deliveries than in unassisted vaginal delivery. However, comparing outcomes after elective cesarean section and planned vaginal delivery, only moderate blood loss (higher in elective cesarean section), neonatal transfer to NICU and neonatal infections (both higher in planned vaginal delivery) differed significantly. CONCLUSIONS: Most studied adverse outcomes increased with increasing maternal age, as did operative delivery. Although emergency operative procedures were associated with an increased risk of adverse outcomes, the absolute risk difference in complications between the modes of delivery was low for the majority of outcomes studied.

The associations of maternal body mass index with birthweight and placental weight. Does maternal diabetes matter? A population study of 106 191 pregnancies.

INTRODUCTION: The aim of this study was to study whether the associations of maternal body mass index with offspring birthweight and placental weight differ by maternal diabetes status. MATERIAL AND METHODS: We performed a population study of 106 191 singleton pregnancies by using data from the years 2009-2012 in the Medical Birth Registry of Norway. We estimated changes in birthweight and in placental weight (in grams) by maternal body mass index by linear regression analysis. RESULTS: In pregnancies of women without diabetes, birthweight increased by 14.7 g (95% confidence interval 14.1-15.2) per unit increase in maternal body mass index, and the increase in placental weight was 4.2 g (95% confidence interval 4.0-4.4). In pregnancies of women with gestational diabetes, the corresponding figures were 11.8 g (95% confidence interval 8.3-15.4) and 2.9 g (95% confidence interval 1.7-4.0). In pregnancies of women with type 1 diabetes we found no significant changes in birthweight or in placental weight by maternal body mass index. Overall, mean birthweight was 513.9 g (95% confidence interval 475.6-552.1) higher in pregnancies involving type 1 diabetes than in pregnancies of women without diabetes. Mean placental weight was 102.1 g (95% confidence interval 89.3-114.9) higher. Also, in pregnancies of women with gestational diabetes, both birthweight and placental weight were higher than in women without diabetes (168.2 g and 46.5 g, respectively). Adjustments were made for maternal body mass index and gestational age at birth. CONCLUSIONS: Birthweight and placental weight increased with increasing maternal body mass index in pregnancies of women without diabetes and in pregnancies of women with gestational diabetes, but not in pregnancies of women with type 1 diabetes. Independent of body mass index, mean birthweight and mean placental weight were highest in pregnancies of women with type 1 diabetes.

Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience.

INTRODUCTION: The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries. MATERIAL AND METHODS: A questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation. RESULTS: Among the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients' clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1:3). CONCLUSIONS: Overall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures.

Sexual activity and functioning after risk-reducing salpingo-oophorectomy: Impact of hormone replacement therapy.

OBJECTIVE: To examine sexual activity and functioning in women after risk-reducing salpingo-oophorectomy (RRSO) compared with the general population (NORM). METHODS: Retrospective cohort study. 294 women who underwent RRSO and 1228 women from the NORM group provided written information based on mailed questionnaires. Sexual pleasure and discomfort scores and frequency of sexual activity were evaluated using the Sexual Activity Questionnaire. RESULTS: The RRSO group reported less sexual pleasure (10.5 vs. 11.9, P=0.009), more discomfort (1.9 vs. 0.83, P<0.001), and less frequent sex than did the controls. Significant associations were observed between a lower pleasure score and being in the RRSO group, older age, history of cancer, low body image, high level of role functioning, and low level of global quality of life (QoL). Further, significant associations were detected between more discomfort and being in the RRSO group, older age, history of cancer, poor body image, and low level of global QoL. Hormone replacement therapy (HRT) use had no impact on pleasure or discomfort score in regression analyses among all the sexually active women. However, in subanalyses of the RRSO group, users of systemic HRT reported less discomfort (1.2 vs. 2.4, P=0.001) than did the nonusers. CONCLUSIONS: After RRSO, women reported significantly less sexual pleasure, more discomfort, and less frequent sex compared with the controls. In the RRSO group, systemic HRT users reported less discomfort than did the nonusers. Health care providers should be attentive to these issues when counseling before and after prophylactic surgery.

Fructose content of low calorie diets: effect on cardiometabolic risk factors in obese women with polycystic ovarian syndrome: a randomized controlled trial.

We aimed to examine whether a whole-grain crispbread (CB) low-fructose, low-calorie diet (LCD) might be superior to a traditional LCD based on fructose-rich liquid meal replacements (LMRs) with respect to improvement of various cardiometabolic risk factors and reproductive hormones. Parallel-group randomised controlled clinical trial. Morbidly obese women with polycystic ovarian syndrome (PCOS) were randomised to either an 8-week CB-LCD or LMR-LCD (900-1100 kcal/day, fructose 17 g/day or 85 g/day). A total of 51 women completed the study. Body weight, fat mass and waist circumference reduced by mean (s.d.) 10.0 (4.8) kg, 7.4 (4.2) kg and 8.5 (4.4) cm, with no significant differences between groups. Total-cholesterol, HDL-cholesterol and Apo-A1 were significantly reduced within both groups (all P values <0.01), with no significant between-group differences. The triacylglycerol and LDL-cholesterol levels were reduced within the LMR group only, with no significant between-group differences. Blood pressure and most measures of glucose metabolism improved significantly in both diet groups, with no significant between-group difference. Uric acid levels rose by 17.7 (46.4) and 30.6 (71.5) µmol/l in the CB and LMR group, respectively, with no significant difference between groups. Gastrointestinal discomfort was significantly and equally reduced in both intervention groups. Free testosterone index was reduced in both groups, with no significant difference between groups. Morbidly obese women with PCOS who underwent either an 8-week low or high-fructose LCD-diet had similar changes in various cardiometabolic risk factors and reproductive hormones. Registration at ClinicalTrials.gov: NCT00779571.

Effect of Previous Chemotherapy on the Quality of Cryopreserved Human Ovarian Tissue In Vitro.

BACKGROUND: Cryopreservation of ovarian tissue has been widely accepted as an option for fertility preservation among cancer patients. Some patients are exposed to chemotherapy prior to ovarian tissue cryopreservation. Consequently, assessment of the developmental capacity of human ovarian tissue after chemotherapy is of primary importance. MATERIALS: In order to study the impact of previous chemotherapy on in vitro development and viability of ovarian follicles, quality control samples from 34 female cancer patients at median age of 15 years (range 1‒35), cryopreserved for fertility preservation before (n = 14) or after (n = 20) initiation of chemotherapy, were thawed and cultured for 7 days. The morphology and developmental stages of ovarian follicles were studied by light microscopy before and after culture. Possible associations between follicular densities, age and exposure to alkylating agents, expressed as cyclophosphamide equivalent dose (CED) were tested. RESULTS: Exposure to chemotherapy significantly impaired the survival and development of ovarian follicles in culture. After seven days, significantly higher densities of intermediary, primary and secondary follicles and lower densities of atretic follicles was detected in the samples collected before chemotherapy. Increasing dose of alkylating agents was identified by multivariate linear regression analysis as an independent predictor of a higher density of atretic follicles, whereas increasing age of the patient predicted a better outcome with less follicle atresia and a higher density of maturing follicles. CONCLUSION: This study provides quantitative in vitro evidence of the impact of chemotherapy on developmental capacity of cryopreserved human ovarian tissue. The results indicate that fertility preservation should be carried out, if possible, before initiation of alkylating agents in order to guarantee better in vitro survival of ovarian follicles. In addition, ovarian samples from younger girls show lower viability and fewer developing follicles in culture.