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.

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.

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.

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.

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.

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.

Female reproductive decline is determined by remaining ovarian reserve and age.

The early decline and loss of female fertility in humans and other species represents an evolutionary paradox. Despite being born with a vast stock of oocytes, females encounter an exhaustion of ovarian reserve and sterility half way through their natural lives. Female reproductive ageing has been proposed to proceed as an ongoing decline in ovarian reserve, determined by remaining ovarian follicle number. However, despite extensive modelling, the respective contributions of intra-, inter-, and extra-ovarian signalling have not been fully characterised. It remains unclear whether reproductive ageing progresses simply as a pre-determined function of remaining ovarian follicles, or as an age-dependent process in humans. Here, we have analysed ovarian response to hormonal stimulation in women who have undergone surgical removal of a single ovary, in order to investigate the relative contributions of intra-, inter, and extra-ovarian signalling on reproductive ageing. Our data show that in unilaterally oophorectomised women, ovarian response to follicle stimulating hormone (FSH) declines beyond levels predicted by a total ovarian follicle pool model of reproductive ageing. Maintenance of ovarian function later in reproductive life, despite the removal of half of the total ovarian reserve, suggests a role for an extra-ovarian age-dependent regulation of reproductive decline. This highlights the need for further work to identify signalling factors that communicate age-related signals between the soma and the germline.

Pregnancy outcome according to male diagnosis after ICSI with non-ejaculated sperm compared with ejaculated sperm controls.

The aim of this study was to describe pregnancy outcome in couples who had undergone ICSI using non-ejaculated sperm from men with non-obstructive azoospermia, obstructive azoospermia and aspermia compared with the outcome of ICSI with ejaculated sperm from men with severe oligozoospermia, treated during the same time period. This nationwide cohort study included all children born after ICSI with non-ejaculated sperm in Norway, from when the method was first permitted in Norway in April 2004 to the end of 2010, resulting in 420 pregnancies and a total of 359 children. In 235 of these children, the father was diagnosed with obstructive azoospermia, in 72 with non-obstructive azoospermia, in 31 with aspermia, and in 21 the male cause was unclassifiable. The control group consisted of 760 children from 939 pregnancies conceived by ICSI with ejaculated sperm. Sex ratio, birth weight, rate of pregnancy loss and congenital malformations were not significantly associated with sperm origin or the cause of male factor infertility.

Endometriosis in adolescence: predictive markers and management.

Endometriosis has long been thought mostly to affect the adult female population. However, awareness of possible endometriosis already in adolescence is now receiving increasing attention. It seems that certain markers in adolescence are associated with a subsequent diagnosis of the disease. These include chronic pelvic pain, severe dysmenorrhea, dysmenorrhea resistant to non-steroidal anti-inflammatory drugs and oral contraceptive pills, and pain interfering with daily activity. Based on current knowledge, it should be possible to diagnose endometriosis before adulthood, thereby alleviating symptoms and possibly limiting sequelae. To do so, knowledge of adolescent endometriosis has to be improved among both health professionals and the public.

Placental weight relative to birthweight in pregnancies with maternal diabetes mellitus.

OBJECTIVES: To study the association of maternal diabetes mellitus with placental weight, birthweight and placental weight-to-birthweight ratio. DESIGN: Population-based study. SETTING: Medical Birth Registry of Norway. POPULATION: All singleton births in Norway during 1999-2008 (n = 536,997). METHODS: We compared the distribution of placental weight z-scores and placental weight-to-birthweight ratio between pregnancies with and without diabetes. The associations of diabetes with placental weight z-scores were also estimated as odds ratios with and without adjustment for birthweight, maternal age, parity, preeclampsia, smoking and cesarean delivery. MAIN OUTCOME MEASURES: Placental weight, birthweight and placental weight-to-birthweight ratio. RESULTS: Mean placental weight was 736.6 g in diabetic pregnancies and 672.1 g in non-diabetic pregnancies. The corresponding birthweights were 3682.1 g and 3557.0 g. In diabetic pregnancies, 26.2% of the placentas were in the highest decile of placental weight z-score, as compared with 9.7% in non-diabetic pregnancies (p < 0.001). The corresponding figures for being in the highest decile of placental weight-to-birthweight ratio were 18.2 and 9.9% (p < 0.001). The crude odds ratio for having a placenta in the highest decile of placental weight z-score was 3.29 (95% confidence interval 3.14-3.45) in diabetic pregnancies with non-diabetic pregnancies as the reference. After adjustment for birthweight and other variables, the odds ratio was 2.42 (95% confidence interval 2.29-2.56). CONCLUSIONS: In diabetic pregnancies, placental weight as well as placental weight relative to birthweight were higher than in non-diabetic pregnancies.

Maternal body mass index and serum concentrations of human chorionic gonadotropin in very early pregnancy.

OBJECTIVE: To study the association of maternal prepregnancy body mass index (BMI) with serum concentrations of hCG in early pregnancy. DESIGN: Cross-sectional study. SETTING: Oslo University Hospital, Norway, 1996-2010. PATIENT(S): Among 3,301 pregnancies with live-born offspring conceived after assisted reproductive techniques, 2,611 women had information on serum hCG concentrations on day 16 after ovulation induction and prepregnancy BMI: 2,110 mothers with singleton and 501 mothers with multiple pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Human chorionic gonadotropin concentration. RESULT(S): Geometric mean hCG concentration was higher in multiple pregnancies (190 IU/L) than in singleton pregnancies (106 IU/L). In singleton pregnancies geometric mean serum concentration decreased from 117 IU/L in women with BMI <20 kg/m(2) to 86 IU/L in women with BMI ≥ 35 kg/m(2). In multiple pregnancies, the corresponding decrease was from 226 IU/L to 130 IU/L. There was a significant negative association of BMI with hCG concentrations log transformed in the study sample as a whole (regression coefficient -0.013), in singleton pregnancies (regression coefficient -0.012), and in multiple pregnancies (regression coefficient -0.03). CONCLUSION(S): Serum hCG concentrations were negatively associated with maternal prepregnancy BMI. One possible explanation may be an effect of adipose tissue-derived signaling molecules on hCG secretion by the implanting embryo.

Interaction between granulosa-lutein cells and monocytes regulates secretion of angiogenic factors in vitro.

BACKGROUND: Leukocyte infiltration and angiogenesis in the forming corpus luteum are prerequisites for normal ovarian function and may also underlie disorders like ovarian hyperstimulation syndrome. We examined whether ovarian angiogenesis could be affected by an interaction between granulosa-lutein (GL) cells and leukocytes. METHODS AND RESULTS: We found that GL cells isolated from the follicular fluid synthesize and secrete the chemokine interleukin-8 (IL-8), which activates IL-8-receptor-specific Ca(2+) and p38 mitogen-activated protein kinase signalling in monocytes and induces a directed migration of these cells towards the chemical gradient. Monocytes were found to further enhance IL-8 release, which suggests that these cells promote a massive leukocyte infiltration of the forming corpus luteum. A possible utility of leukocyte infiltration is the modulation of angiogenesis. We found that GL cells induce migration and capillary tube formation by endothelial cells in vitro. Furthermore, monocytes altered the profile of angiogenic factors released by GL cells, which supports the theory that an interaction between GL cells and leukocytes regulates ovarian angiogenesis. In addition, we found a correlation between increased secretion of pro-angiogenic cytokines and number of oocytes collected during IVF, which suggests that ovarian angiogenesis is related to the clinical response during ovarian stimulation. CONCLUSIONS: An intricate communication may exist between infiltrating leukocytes and ovarian GL cells during the formation of corpus luteum, affecting neo-vascularization of the luteal tissue.

Sustained fertility from 22 to 41 years of age in women with polycystic ovarian syndrome.

BACKGROUND: Subfertility due to chronic anovulation is common in women with polycystic ovary syndrome (PCOS) and is often treated with IVF. Women with PCOS have an increased ovarian follicle and oocyte count, increased ovarian reserve and/or a slower rate of follicle atresia. If so, one would expect women with PCOS to display a delayed reduction in fertility with advancing age as compared with eumenorrheic women. METHODS: To test this hypothesis, we compared oocyte count and live birth rates among two groups undergoing IVF, 500 women with PCOS and 500 eumenorrheic women with infertility due to tubal factor only. RESULTS: Across the age range of 22-41 years, oocyte count and live birth rates remained stable in women with PCOS. In the eumenorrheic comparison group, these parameters decreased significantly with age. CONCLUSIONS: Women with PCOS display sustained fertility with advancing age as compared with infertile eumenorrheic women.

Spermatogenesis and fertility outcome in male hypogonadotrophic hypogonadism.

OBJECTIVE: The objective of this retrospective study of male patients with hypogonadotrophic hypogonadism (HH) was to assess the outcome of fertility after induction of spermatogenesis by gonadotrophin injections. METHODS: During 1995-2005 17 men with HH were referred to our department for gonadotrophin treatment to stimulate spermatogenesis. RESULTS: Genetic/idiopathic hypogonadotrophic hypogonadism (IHH) was the most common cause (n = 10) followed by post-operative pituitary failure in three cases. In genetic/IHH, 5 out of 10 cases were born in the Middle East. Gonadotrophin injections induced spermatogenesis in 12 out of 13 HH men indicated by presence of ejaculated motile spermatozoa. All men with proved spermatogenesis and a paternity desire became fathers, five through assisted reproduction with intracytoplasmic sperm injection. A total of 16 children were born as a result of gonadotrophin therapy. Three spontaneously conceived singletons and two twin couples after assisted reproduction were born preterm. Two children from two separate dichorionic twin couples were diagnosed with congenital malformations. CONCLUSIONS: Gonadotrophin therapy is successful for men with HH aiming to initiate or re-establish spermatogenesis. Despite low sperm output in some of these men, the rate of pregnancies both spontaneous and after assisted reproduction, was high. More children than expected were born preterm.

Ten-year follow-up after conservative treatment of stress urinary incontinence.

A follow-up study was done in 33 women 10 years after they had participated in a study on conservative treatment of stress urinary incontinence. The evaluation included a 24-h pad test, a short stress test, and two validated quality of life questionnaires. Currently, five women (15%) were still doing pelvic floor muscle training at least twice per week. During the interim, 15 (47%) women had undergone stress incontinence surgery, and 12 (80%) of these were continent. Among the 18 non-operated women, only one (6%) was continent. The difference is statistically highly significant (p < 0.0001). In conclusion, 10 years after conservative treatment of stress incontinence, 85% of the women had stopped conservative treatment, and 94% of those not operated were still incontinent. Significantly more of those who had undergone interval incontinence surgery were now continent.

Postoperative voiding, bacteriuria and urinary tract infection with Foley catheterization after gynecological surgery.

BACKGROUND: The use of bladder drainage to avoid urinary retention after gynecological surgery is more or less custom based, and duration of drainage varies considerably. In this paper the use of 1-day drainage by transurethral Foley catheter was investigated with regard to impaired voiding, asymptomatic bacteriuria, and urinary tract infection. Furthermore, the use of methenamine hippurate was studied with regard to postoperative asymptomatic bacteriuria and urinary tract infection. METHODS. This summary is based on six published papers totaling 917 patients. In three case series, 1-day catheterization was used in women undergoing gynecological laparotomy, colposuspension, or vaginal plastic surgery. To compare 1- and 3-day Foley catheterization, two open, randomized trials were performed on women undergoing vaginal plastic surgery or colposuspension. The last study was a double-blind trial between methenamine hippurate and placebo as prophylaxis against urinary tract infection and asymptomatic bacteriuria using 1-day catheterization. RESULTS: Postoperative voiding problems and urinary tract infection occurred infrequently with 1-day catheterization, and no more frequently than with catheterization for three days. Methenamine hippurate decreased the incidence of urinary tract infection and asymptomatic bacteriuria by 80 and 40%, respectively. CONCLUSIONS: One-day bladder drainage by transurethral Foley catheter may be used routinely in common gynecological surgery with a low rate of voiding problems, asymptomatic bacteriuria, and urinary tract infection. Methenamine hippurate prophylaxis effectively reduces postoperative urinary tract infection.