School-age outcomes among IVF-conceived children: A population-wide cohort study.

BACKGROUND: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. METHODS AND FINDINGS: Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in ≥2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program-Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Inverse probability weighting with regression adjustment was used to estimate population average causal effects. The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of -0.3% (95% CI -3.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI -0.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school. CONCLUSIONS: In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians.

American Heart Association ideal cardiovascular health score and subclinical atherosclerosis in 22-35-year-old adults conceived with and without assisted reproductive technologies.

STUDY QUESTION: Is ART related with the association of American Heart Association (AHA) ideal cardiovascular health score and markers of subclinical atherosclerosis? SUMMARY ANSWER: The associations between AHA score and markers of subclinical atherosclerosis in ART and non-ART groups were similar in magnitude. WHAT IS KNOWN ALREADY: Long-term consequences of ART on cardiovascular health are unknown. STUDY DESIGN, SIZE, DURATION: The study cohort for the cross-sectional analyses consisted of 172 ART-conceived and 78 non-ART conceived individuals of same age (range 22-35 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Cardiovascular risk factor status was evaluated with American Heart Association (AHA) ideal cardiovascular health score consisting of seven factors (body mass index, blood pressure, total cholesterol, glucose, diet and physical activity, non-smoking). Carotid artery intima-media thickness (cIMT), arterial pulse-wave velocity (PWV) and retinal microvascular parameters were evaluated as markers of early atherosclerosis. Group comparisons in continuous variables were performed with t-tests. For categorical variables, comparisons were performed with chi-square tests. The relationships between AHA score and the markers of atherosclerosis were examined with linear regression analyses adjusted for age and sex. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference in AHA ideal health score between the ART and non-ART groups; mean (SD) scores were 4.1(1.4) versus 4.0(1.5), respectively, P = 0.65. No differences were observed between groups for any individual ideal health metric (P always >0.2). AHA score was not associated with cIMT or retinal measures in either group (P always >0.05). An inverse association was observed between AHA score and PWV in the ART group (beta (95% CI) -0.18(-0.26 to -0.10)). A numerically similar relationship was observed in the smaller non-ART group (-0.19(-0.39 to 0.01)). LIMITATIONS, REASONS FOR CAUTION: Even though this cohort is among the largest ART studies with extensive cardiovascular data, the sample is still relatively small and the statistical power is limited. As the study population was still in early adulthood, we were not able to evaluate the associations with clinical cardiovascular events, but utilized non-invasive methods to assess early markers of subclinical atherosclerosis. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that ART-conceived individuals do not have increased vulnerability for cardiovascular risk factors. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a National Health & Medical Research Council Project Grant (APP1099641), The Royal Children's Hospital Research Foundation, Monash IVF Research and Education Foundation, and Reproductive Biology Unit Sperm Fund, Melbourne IVF. The authors have no conflicts of interest relevant to this article to disclose.

The Fertility Management Experiences of Australian Women with a Non-communicable Chronic Disease: Findings from the Understanding Fertility Management in Contemporary Australia Survey.

Introduction Despite the considerable and increasing proportion of women of reproductive age with a chronic non-communicable disease (NCD) and the potential adverse implications of many NCDs for childbearing, little is known about the fertility management experiences of women with an NCD, including their contraceptive use, pregnancy experiences and outcomes, and reproductive health care utilisation. The aim of this study was to investigate the fertility management experiences of women with an NCD and draw comparisons with women without an NCD. Method A sample of 18-50 year-old women (n = 1543) was randomly recruited from the Australian electoral roll in 2013. Of these women, 172 women reported a physical, chronic non-communicable disease: diabetes, arthritis, asthma, hypertension, heart disease, thyroid disorders, and cystic fibrosis. Respondents completed an anonymous, self-administered questionnaire. Factors associated with fertility management were identified in multivariable analyses. Results Women who reported having an NCD were significantly more likely than women who did not report an NCD to have ever been pregnant (75.9 vs. 67.5%, p = 0.034), have had an unintended pregnancy (33.47 vs. 25.5%, p = 0.026), and have had an abortion (20.3 vs. 14.2%, p = 0.044); they were less likely to consult a healthcare provider about fertility management (45.0 vs. 54.4%, p = 0.024). Similar proportions were using contraception (48.8 vs. 54.5%, p = 0.138). Conclusion The findings have implications for healthcare providers and women with an NCD and highlight the importance of addressing possible assumptions about the inability of women with an NCD to become pregnant, and ensuring women receive information about suitable methods of contraception and pre-pregnancy care.

Fertility management experiences of women with polycystic ovary syndrome in Australia.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are usually told that the condition is associated with fertility difficulties. However, little is known about their fertility management including contraceptive use, childbearing desires, and pregnancy outcomes. AIM: To compare the fertility management experiences and outcomes of Australian women with and without PCOS. METHOD: The 2013 Australian electoral roll was used to identify a random sample of 18- to 50-year-old women who were sent the Understanding Fertility Management in Australia survey to be completed anonymously. Factors associated with fertility management and outcomes were identified in multivariable analyses. RESULTS: Among the 1543 women who completed and returned the survey, 113 (7.3%) reported having PCOS. Women with PCOS reported a similar rate of current contraceptive use as women without PCOS (50.4% vs. 52.6%, p = .66). However, they were significantly younger at first pregnancy (24.9 vs. 26.8 years, p = .015), more likely to have consulted a health professional about fertility management (OR: 3.86, 95% CI: 2.50-5.96, p < .001), and perceive that it would be difficult to conceive (OR: 2.31, 95% CI: 1.41-3.79, p = .001) than women without PCOS. There were no significant differences in the number of desired children, unintended pregnancies, live births, abortions or miscarriages between women with and without PCOS. CONCLUSION: These findings indicate that women with PCOS need more nuanced information about their fertility potential. While they may experience fertility difficulties because of their condition, they should also be informed that they can conceive spontaneously and need reliable contraception to avoid pregnancy when it is not wanted.

Reproductive experiences of women who cryopreserved oocytes for non-medical reasons.

STUDY QUESTION: What are the reproductive experiences of women who cryopreserve oocytes for non-medical reasons? SUMMARY ANSWER: One in three women had been pregnant at some stage in their lives and while most still wanted to have a child or another child, very few had used their stored oocytes, predominantly because they did not want to be single parents. WHAT IS KNOWN ALREADY: The number of healthy women who freeze oocytes to avoid age-related infertility is increasing. Evidence about reproductive outcomes after oocyte cryopreservation for non-medical reasons is needed to help women make informed decisions. STUDY DESIGN SIZE, DURATION: A cross-sectional survey was carried out. Study packs which included a self-administered questionnaire were mailed by clinic staff to 193 eligible women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who had stored oocytes for non-medical reasons at Melbourne IVF, a private ART clinic, between 1999 and 2014 were identified from medical records and invited to complete an anonymous questionnaire about their reproductive histories and experience of oocyte cryopreservation. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 10 survey packs were returned to the clinic marked 'address unknown'. Of the 183 potential respondents, 96 (53%) returned the questionnaire. One respondent provided only free-text comments, thus data from 95 respondents were compiled. The mean age at the time of freezing oocytes was 37.1 years (SD ± 2.6, range: 27-42) and the average number of oocytes stored was 14.2 (SD ± 7.9, range: 0-42); 2% had attempted to store oocytes but had none suitable for freezing, 24% had stored <8 oocytes, 35% had 8-15, 25% had 16-23 and 14% had stored >23 oocytes. About one-third of respondents (34%) had been pregnant at some point in their lives. Six women (6%) had used their stored oocytes and three of them had given birth as a result. The main reason for not using stored oocytes was not wanting to be a single parent. Of the 87 (91%) women who still had oocytes stored, 21% intended to use them while 69% indicated that their circumstances would determine usage. The mean number of children respondents would ideally have liked to have was significantly higher than the number of children they expected to have (2.11 versus 1.38, P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The limitations are inherent to any anonymously completed questionnaire: participation bias, missing data and the possibility that some questions or response alternatives may have been ambiguous. WIDER IMPLICATIONS OF THE FINDINGS: The findings add to the very limited evidence about the reproductive outcomes experienced by women who freeze oocytes for non-medical reasons and can be used to help women make informed decisions about whether to store oocytes. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Melbourne IVF. K.H. has received honoraria from Merck-Serono, J.M. is a clinician at Melbourne IVF, F.A. is a Melbourne IVF employee, J.F. is supported by a Monash Professorial Fellowship and the Jean Hailes Professorial Fellowship which receives funding from the L and H Hecht Trust, managed by Perpetual Trustees Pty Ltd. M.K., N.P., M.H., M.P. and C.B. have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Health outcomes of school-aged children conceived using donor sperm.

The use of donor sperm is increasing, yet limited information is available about the health and development of children conceived from donor sperm. This retrospective descriptive study aimed to assess health and development in a cohort of school-aged children who were conceived using donor sperm. Participants included 224 children, aged 5-11 years, who were conceived using donor sperm. Participants' mothers completed a questionnaire comprising validated scales examining their child's current and past physical, psychosocial and mental health, healthcare needs and child development, as well as the mothers' health and wellbeing. At the conclusion of the study, the response rate was 296 out of 407 (72.7%), with a participation rate of 224 out o 407 (55.0%). Compared with the normative Australian population, sperm donor-conceived children had similar physical, psychosocial and mental health and development. A modest increase in healthcare needs was evident. The study concludes that in school-aged children conceived using donor sperm, most aspects of child health and wellbeing are similar to the general population.

Clinical review of 24-35 year olds conceived with and without in vitro fertilization: study protocol.

BACKGROUND: Children conceived by assisted reproductive technologies (ART) currently comprise 4% of Australian births. The manipulation of biological parameters related to fertilization and implantation are integral to successful ART but potentially pose a risk to the longer-term health of the offspring. There is consensus that many common adult health problems (particularly cardiovascular, metabolic and respiratory conditions) have their origins in early life, possibly before birth, and that risk trajectories track through childhood until clinical disease manifests in adulthood. Early life epigenetic variation may play a role in this process. However little is known about the long-term health of individuals conceived by ART. In a previous study, based on telephone-interviews, we found that young adults conceived by in vitro fertilization (IVF) had significantly more maternal reported atopic respiratory, endocrine, nutritional, and metabolic conditions than non-IVF conceived matched controls. Here we outline the protocol for a follow-up biomedical assessment of this cohort and a questionnaire to obtain information on potential confounders. METHODS: We are conducting a clinical review of an existing, well characterised cohort comprising 547 IVF-conceived adults and 549 matched controls. We are measuring cardiovascular intermediate phenotypes, metabolic parameters and respiratory function, complemented by epigenome-wide DNA methylation analysis. A pilot study demonstrated the feasibility of our proposed protocol and its acceptability to participants. Participants attend a 2-3 h clinical assessment and complete a study-specific online questionnaire. Measurements include: 1) cardiovascular phenotypes: carotid artery intima-media thickness and distensibility, retinal vascular calibre, resting blood pressure, pulse wave velocity and pulse wave analysis; 2) respiratory function: spirometry, plethysmography, multiple breath washout; 3) auxology: height, weight, waist circumference, bio-impedance. Blood is collected for 4) biomarkers of cardiometabolic profile including inflammatory markers and 5) epigenetic analysis. DISCUSSION: Recruitment for this clinical review is challenging as many of the participants have moved to regional, interstate or international locations. Additionally, many female participants are pregnant or breastfeeding, and are therefore ineligible. Nevertheless, comprehensive strategies have been developed to optimize recruitment. Given the increasing use of IVF and related technologies, the potential long-term consequences for risk of common adult diseases is an important clinical and public health issue.

Subjective meanings of 'unintended' pregnancy: interviews from understanding fertility management in contemporary Australia.

Unintended pregnancy can be difficult to identify and conceptualise. We aimed to understand how unintended pregnancies are constructed, explained and situated in a reproductive life. A total of 41 women and 7 men aged 20-50 years were interviewed in depth. Transcripts were analysed using iterative hermeneutic techniques informed by narrative theory. Of 34 participants who had been pregnant or had a partner in pregnancy, 12 women and 1 man described 23 'unintended' pregnancies, about half of which ended in abortion. Their accounts reveal that an unintended pregnancy is identified subjectively, that the same pregnancy may be identified by one partner in the pregnancy as unintended and by the other as intended, and that a researcher's supposedly objective assessment of an unintended pregnancy may be inconsistent with the assessment of the woman who experienced it. A pejorative discourse was evident, predominantly among participants who did not report having an unintended pregnancy: women use an 'unintended' pregnancy to entrap men. Accounts from five participants reporting an unintended pregnancy were selected for illustration. An appreciation of the role such a pregnancy might play in an individual life requires a nuanced understanding of the complexity of human experience and a resistance to simple binary categorisation.

Sociodemographic characteristics associated with the use of effective and less effective contraceptive methods: findings from the Understanding Fertility Management in Contemporary Australia survey.

OBJECTIVE: Unintended pregnancy and abortion may, in part, result from suboptimal use of effective contraception. This study aimed to identify sociodemographic factors associated with the use of effective and less effective methods among women and men of reproductive age living in Australia. METHODS: In a cross-sectional national survey, 1544 women and men aged 18-51 were identified as being at risk of pregnancy. Chi-square and logistic regression analyses were used to assess the sociodemographic factors related to contraceptive use. RESULTS: Most respondents (n = 1307, 84.7%) reported using a method of contraception. Use of any contraceptive was associated with being born in Australia (Odds Ratio [OR] 1.89; 95% Confidence Interval [CI]1.186, 3.01; p = .008), having English as a first language (OR 1.81; 95% CI: 1.07, 3.04; p = .026), having private health insurance (OR 2.25; 95% CI 1.66, 3.04; p < .001), and not considering religion important to fertility choices (OR 0.43; 95%CI 0.31, 0.60; p < .001). A third used effective contraceptive methods (n = 534, 34.6%; permanent methods: 23.1%, and long-acting reversible contraception (LARC): 11.4%). Permanent methods were more likely to be used in rural areas (OR 0.62; 95%CI 0.46, 0.84; p = .002). Use of the least effective, short-term methods was reported by nearly half (condoms: 25.6%, withdrawal: 12.5%, and fertility-awareness-based methods: 2.8%). Those who relied on withdrawal were more likely to live in a metropolitan area (OR 2.85; 95% CI 1.95, 4.18; p < .001), and not have private health insurance (OR 0.52; 95% CI 0.38, 0.71; p < .001). CONCLUSIONS: Targeted promotion of the broad range of available contraceptives may raise awareness and uptake of more effective methods and improve reproductive autonomy in certain population groups.

Characteristics and circumstances of women in Australia who cryopreserved their oocytes for non-medical indications.

OBJECTIVE: This study aimed to explore the characteristics and circumstances of women who cryopreserved their oocytes for non-medical indications and their reasons for cryopreservation. BACKGROUND: Oocyte cryopreservation for non-medical reasons is becoming increasingly common. Little is known about women who freeze their oocytes in this context. METHODS: All women who had cryopreserved oocytes for non-medical indications at a large Australian fertility treatment centre from 1999 to 2014 were invited to complete an anonymous postal survey. RESULTS: Of the 193 questionnaires mailed, 10 were returned to sender; 96/183 (53%) were completed and returned. Most respondents had completed tertiary education (90%) and were employed in professional occupations (89%). At the time of oocyte cryopreservation, 48% of women were aged at least 38 years (range 28-44 years). Most (90%) women were single when their oocytes were frozen. The lack of a partner or having a partner unwilling to commit to fatherhood were the most common reasons for oocyte freezing, which was viewed as an investment in hope against the possibility of remaining in these predicaments. Some women reported that discussions in the media and interactions with peers influenced their decisions. A few women were influenced by tests indicating a low ovarian reserve. CONCLUSION: These data provide new evidence about women's characteristics, circumstances, and reasons for oocyte cryopreservation for non-medical indications that do not support pejorative conceptualisations of these women as selfish and hedonistic.

Ovarian suppression in a marsupial following single treatment with a gonadotrophin-releasing hormone agonist in microspheres.

The effect of treatment with Lucrin Depot (1 month), a microsphere gonadotrophin-releasing hormone agonist preparation, was investigated in the fat-tailed dunnart (Sminthopsis crassicaudata) as a potential strategy to synchronise cycling. The status of the ovaries (ovarian size, number and size of Graafian follicles and corpora lutea) and reproductive tract (weight, vascularity and muscularity) in twelve untreated females were assessed to establish the activity parameters for randomly selected cycling animals. Thirty-six females were treated with 1mgkg-1 (n=12), 10mgkg-1 (n=12) or 20mgkg-1 (n=12) Lucrin Depot. At 4, 6 and 8 weeks the reproductive tracts were assessed using the criteria developed in the untreated females. All of the females treated with 10mgkg-1 showed suppression at 4 weeks and 25% showed return of reproductive activity at 8 weeks. A dose of 1mgkg-1 did not appear to suppress reproductive activity and 20mgkg-1 gave equivocal results, with evidence of both suppression and activity. The results indicate that Lucrin Depot appears to be a promising agent to regulate and potentially synchronise breeding activity in the fat-tailed dunnart.

What is the contribution of embryo-endometrial asynchrony to implantation failure?

PURPOSE: The synchronized development of a viable embryo and a receptive endometrium is critical for successful implantation to take place. The aim of this paper is to review current thinking about the importance of embryo-endometrial synchrony in in vitro fertilization (IVF). METHODS: Detailed review of the literature on embryo-endometrial synchrony. RESULTS: By convention, the time when the blastocyst first attaches and starts to invade into the endometrium has been defined as the 'window of implantation'. The term window of implantation can be misleading when it is used to imply that there is a single critical window in time that determines whether implantation will be successful or not. Embryo maturation and endometrial development are two independent continuous processes. Implantation occurs when the two tissues fuse and pregnancy is established. A key concept in understanding this event is developmental 'synchrony', defined as when the early embryo and the uterus are both developing at the same rate such that they will be ready to commence and successfully continue implantation at the same time. Many different events, including controlled ovarian hyperstimulation as routinely used in IVF, can potentially disrupt embryo-endometrial synchrony. There is some evidence in humans that implantation rates are significantly reduced when embryo-endometrial development asynchrony is greater than 3 days (±1.5 days). CONCLUSIONS: Embryo-endometrial synchrony is critical for successful implantation. There is an unmet need for improved precision in the evaluation of endometrial development to permit better synchronization of the embryo and the endometrium prior to implantation.

Long-acting reversible contraception: Findings from the Understanding Fertility Management in Contemporary Australia survey.

OBJECTIVES: The aim of this research was to investigate awareness, perceived reliability and consideration of use of long-acting reversible contraception (LARC) among Australians of reproductive age. METHODS: A sample of 18- to 50-year-old women and men (N = 2235) was randomly recruited from the Australian electoral roll in 2013. Respondents completed a self-administered, anonymous questionnaire. Data were weighted to reduce non-response bias. Factors associated with perceived reliability and consideration of use of LARC were identified in multivariable analyses. RESULTS: Most respondents had heard of implants (76.5%) and intrauterine contraception (63.7%). However, most did not think implants (56.3%) or IUDs (63.9%) were reliable and would not consider using implants (71.6%) or IUDs (77.5%). Those significantly more likely to perceive LARC as reliable were younger, did not regard religion as important in fertility choices, had private health insurance, had been pregnant and had had an abortion; and women who had a partner. Those more likely to consider using LARC were younger and did not regard religion as important in fertility choices; women who had private health insurance, lived in an area of socioeconomic advantage and had had an abortion; and men without a partner, born in Australia and comfortable talking to a health care provider about contraceptive matters. CONCLUSIONS: Despite high awareness of LARC among Australian adults, its perceived reliability and willingness to use it remain low in certain groups. Targeted interventions that aim to increase knowledge of the benefits and reliability of LARC and allow informed use are recommended.

A randomised controlled trial of intra-uterine insemination versus in vitro fertilisation in patients with idiopathic or mild male infertility.

BACKGROUND: The cause of infertility is unexplained or poorly explained in 30-40% of couples undergoing standard investigations, and treatment ranges from expectant management to IUI and IVF. AIMS: The aim of this study was to compare the clinical pregnancy rates and costs of intra-uterine insemination (IUI) and in vitro fertilisation (IVF) in women where the same ovarian stimulation led to the development of two or three mature follicles. METHODS: A randomised controlled clinical trial compared the efficacy of IUI and IVF in a tertiary fertility centre (ISRCTN28780587). Primary outcome measures were fetal heart positive pregnancy rate and cost per live birth. The selection criteria were age: females 18-42 years and males 18-60 years, infertility for one year or more, no IVF or IUI for 12 months prior to the trial, and no coital, tubal or ovulatory disorders, oligospermia, untreated endometriosis or contraindication for multiple pregnancy. All women (n = 102) had the same dose FSH stimulation protocol. Those who developed two or three preovulatory follicles were randomised 3:1 to IUI (n = 33) or IVF (n = 10). IUI or IVF was performed 36 h after hCG administration with single or double embryo transfer on day two. RESULTS: Clinical pregnancy rates (40% vs 12%, P = 0.04) and live birth rate (40% vs 6%, P = 0.01) were higher for IVF than IUI. The cost per live birth was AU$8735 for IVF compared with $42,487 for IUI. CONCLUSIONS: This study provides evidence that IVF is more successful and cost-effective than IUI using the same doses of FSH. Further confirmatory studies are required.

Age, mode of conception, health service use and pregnancy health: a prospective cohort study of Australian women.

BACKGROUND: There is limited evidence about the ways in which maternal age and mode of conception interact with psychological, sociodemographic, health and health service factors in governing pregnancy health. The aim of this study was to establish in what ways maternal age and mode of conception are associated with, health behaviours, health service use and self-rated physical and mental health during pregnancy. METHOD: A prospective cohort study was conducted in a collaboration between universities, infertility treatment services and public and private obstetric hospitals in Melbourne and Sydney, Australia,. Consecutive cohorts of nulliparous English-literate women at least 28 weeks pregnant who had conceived through ART (ARTC) or spontaneously (SC) in three age-groups: 20-30; 31-36 and at least 37 years were recruited. Data were obtained via structured individual telephone interviews and self-report postal questionnaires at recruitment and four months postpartum. Study-specific questions assessed: sociodemographic characteristics; reproductive health; health behaviours and health service use. Standardized instruments assessed physical health: SF 12 Physical Component Score (PCS) and mental health: SF12 Mental Component Score (MCS); State Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale. The main outcome measures were the SF 12 PCS, SF12 MCS scores and pregnancy-related hospital admissions. RESULTS: Of 1179 eligible women 791 (67%) participated, 27 had fertility treatment without oocyte retrieval and were excluded and 592/764 (78%) completed all pregnancy assessments. When other factors were controlled speaking a language other than English, having private health insurance and multiple gestation were associated with worse physical health and having private health insurance and better physical health were associated with better mental health. Pregnancy-related hospital admissions were associated with worse physical health and multiple gestation. CONCLUSIONS: Maternal age and mode of conception are not associated with pregnancy health and health service use when sociodemographic factors are considered.

Assisted conception, maternal age and breastfeeding: an Australian cohort study.

AIM: To establish the relationships between age, mode of conception and breastfeeding. METHOD: Consecutive cohorts of nulliparous women >25 weeks pregnant who had conceived through ART (ARTC) or spontaneously (SC) in three age groups ≤30, 31-36 and ≥37 years were recruited. Data were obtained via telephone interviews and postal questionnaires in late pregnancy and 4 months postpartum. Sociodemographic characteristics, reproductive health, birth and breastfeeding experiences were assessed by study-specific questions. Self-rated general health and symptoms of depression and anxiety were assessed with standardized psychometric instruments. Main outcomes were exclusive breastfeeding at discharge from maternity hospital and 4 months postpartum. RESULTS: Of 1179 eligible women, 791 (67%) participated; 549 (93%) had singleton infants, provided complete data and were included in analyses. Overall, 37.2% of participants aged ≤30, 33% aged 31-36 and 55.1% aged ≥37 years experienced Caesarean births. Regardless of age, compared with the SC group, ARTC women had twice the rate of Caesareans prior to labour. Controlling for other factors, exclusive breastfeeding rates at hospital discharge and 4 months postpartum were lowest amongst ARTC women who experienced Caesarean prior to labour (p < .001). CONCLUSION: Independent of age, assisted conception increases the risk conferred by Caesarean birth to breastfeeding initiation and maintenance.

Spontaneous conceptions within two years of having a first infant with assisted conception.

BACKGROUND: Australian data regarding spontaneous conceptions following a live birth conceived by assisted reproductive technologies (ART) have not yet been reported. AIMS: This study aimed to determine the incidence of spontaneous conceptions within 18-24 months after women had a first infant conceived by ART (ARTC) or spontaneously conceived (SC). Factors associated with spontaneous pregnancies in women with ARTC first infants were investigated. MATERIALS AND METHODS: Nulliparous women were recruited through ART clinics (n = 297) and maternity hospitals (n = 295) in Melbourne and Sydney, Australia. Participants were interviewed in pregnancy and when their first infants were aged 18-24 months. Information was collected on pregnancies since the first infant's birth. The outcome was any subsequent conception during this period. RESULTS: Follow-up data were available for 198 women with SC first infants and 236 women with ARTC first infants, 94 (40%) of whom had further ART following the first birth. Spontaneous conceptions had occurred in 40% of women with SC first infants and 33% of women with ARTC first infants who had not had subsequent ART. Twenty-four per cent of pregnancies after the birth of SC first infants were unexpected, compared with 61% of subsequent pregnancies (without further treatment) after the birth of ARTC first infants (P < 0.001). Subsequent, spontaneous pregnancies in women with ARTC first infants were significantly associated with unexplained infertility and shorter partner relationship duration. DISCUSSION: Discussion about contraception is recommended if women with ARTC first infants do not wish to have more children or wish to delay subsequent pregnancies.

Single embryo transfer reduces the risk of perinatal mortality, a population study.

STUDY QUESTION: Do births following single embryo transfers (SET) have a reduced risk of perinatal mortality compared with those following double embryo transfers (DET)? SUMMARY ANSWER: SET is associated with reduced risk of perinatal mortality compared with DET. WHAT IS KNOWN ALREADY: Fetal, neonatal and perinatal mortality are important indicators for monitoring pregnancy and childbirth, particularly for births following assisted reproductive technology (ART) treatments. Following the introduction of SET, there has been a decline in the perinatal mortality rate (PMR) among babies born after ART in Australia and New Zealand. STUDY DESIGN, SIZE, DURATION: This population study (census) included 50,258 births of ≥ 20 weeks gestation and/or ≥ 400 g of birthweight following embryos transfer cycles in Australia and New Zealand during the period 2004-2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: The PMR was calculated according to the number of embryos transferred and other demographic and treatment-related factors. Perinatal deaths were defined as the number of fetal deaths (stillbirths) plus the number of neonatal deaths (deaths that occur before 28 days after birth). MAIN RESULTS AND THE ROLE OF CHANCE: The PMR was 16.2 per 1000 births (n= 813). Of the 813 perinatal deaths, 630 were fetal deaths and 183 neonatal deaths. Twins had a significantly higher PMR (27.8 per 1000 births) than singletons (12.4 per 1000 births). The risk of perinatal mortality for all births following DET was 53% higher than for all births following SET (adjusted risk ratio 1.53, 95% confidence interval (95% CI): 1.29-1.80). Births following fresh DET had a 58% increased risk of perinatal mortality compared with births following fresh SET (risk ratio 1.58, 95% CI: 1.32-1.90). LIMITATIONS, REASONS FOR CAUTION: Information on outcomes was missing from <1% of clinical pregnancies recorded in Australian and New Zealand Assisted Reproduction Database for the study period. There are no data on the timing of fetal death, the cause of perinatal death or on late termination of pregnancy at ≥ 20 weeks' gestation. WIDER IMPLICATIONS OF THE FINDINGS: Double and higher order embryo transfer is associated with a higher risk of perinatal mortality when compared with SET. The number of embryos transferred is determined by the clinician with consent of the patient and is a modifiable treatment factor. SET should be advocated as the first-line management in ART as it is the single most effective public health intervention for preventing excess perinatal mortality among ART pregnancies. STUDY FUNDING/COMPETING INTEREST(S): Nil.

Reproductive function in men conceived with in vitro fertilization and intracytoplasmic sperm injection.

OBJECTIVE: To determine the semen quality and reproductive hormones of men conceived by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) compared with men conceived without assisted reproductive technology (ART). DESIGN: Cohort study. SETTING: IVF centers in Victoria and the Western Australian Raine Study. PATIENT(S): Men conceived with IVF/ICSI and men conceived without ART aged 18-25 years. INTERVENTION(S): Clinical review. MAIN OUTCOME MEASURE(S): The primary outcome was the prevalence of severe oligozoospermia (sperm concentration, <5 million/mL). The secondary outcomes were total sperm count, total and progressive motility, total motile count, normal morphology, and serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). RESULTS: There was no difference in the prevalence of severe oligozoospermia between 120 men conceived with IVF/ICSI and 356 men conceived without ART (9% vs. 5.3%). Men conceived with IVF/ICSI had similar sperm concentration, total sperm count, and total motile count but lower mean total (55.3% vs. 60.6%) and progressive (44.7% vs. 53.9%) sperm motility with higher mean normal morphology (8.5% vs. 5.4%). Differences in progressive motility (ß, -9.9; 95% confidence interval [CI], -16.7 - -3.0), normal morphology (ß, 4.3; 95% CI, 3.0-5.7), and proportion with abnormal morphology (adjusted odds ratios, 0.1; 95% CI, 0.04-0.5) remained significant after adjusting for confounders. Men conceived with IVF/ICSI had lower mean FSH (3.3 IU/L) and LH (3.9 IU/L) levels and higher mean testosterone levels (19.1 nmol/L) than controls (4.2 IU/L, 11.0 IU/L, and 16.8 nmol/L). CONCLUSION: This study of men conceived with IVF/ICSI found similar sperm output to men conceived without ART. Overall, the results are reassuring.