How to talk to young adults about fertility.

RESEARCH QUESTION: How knowledgeable are Danish young adults about fertility and what are their attitudes towards learning about their reproductive biology? DESIGN: The study was conducted at different educational institutions with 11 focus-group discussions that included a total of 47 participants (aged 18-29 years). Qualitative content analysis was used. The participants' fertility knowledge score was measured using the Cardiff Fertility Knowledge Scale. RESULTS: The participants had an overall fertility knowledge score of 54%. Focus-group data showed that they thought it was important to learn about fertility and how to protect their fertility potential regardless of whether or not they wanted children. Providing knowledge is like planting a seed in the young adults. They wanted to hear about fertility in multifaceted ways and formats, and believed the information should be delivered by professionals, but developed in partnership with young people. The double-edged sword of knowledge and the consequence of knowledge made them hesitant or less open to learning. CONCLUSIONS: Recommendations from this study are to tailor fertility information to young people, with due cognisance of their developmental stage, and ideally from an earlier age.

Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility.

It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

Infertility, pregnancy loss and assisted reproduction in women with asthma: a population-based cohort study.

STUDY QUESTION: Is the chance of childbirth, and risk of infertility, pregnancy loss and need for assisted reproduction different for women with asthma compared to women without asthma? SUMMARY ANSWER: Women with asthma had comparable chances of giving birth compared to the reference population, however, their risk of both infertility and pregnancy loss, as well their need for medically assisted reproduction, was higher. WHAT IS KNOWN ALREADY: Reproductive dysfunction has been reported among women with asthma, including longer time to pregnancy, increased risk of pregnancy loss and a higher need of medically assisted reproduction, but their risk of clinical infertility is unknown. STUDY DESIGN, SIZE, DURATION: This longitudinal register-based cohort study included all women with a healthcare visit for delivery, infertility, pregnancy loss or induced abortion in the southernmost county in Sweden, over the last 20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the Skåne Healthcare Register, we identified all women aged 15-45 between 1998 and 2019, who received a diagnosis of asthma before their first reproductive outcome (n = 6445). Chance of childbirth and risk of infertility, pregnancy loss and assisted reproduction were compared to a healthcare seeking population of women without any asthma (n = 200 248), using modified Poisson regressions. MAIN RESULTS AND THE ROLE OF CHANCE: The chance of childbirth was not different between women with asthma versus those without, adjusted risk ratio (aRR) = 1.02, 95% CI: 1.01-1.03. The risk of seeking care for infertility was increased, aRR = 1.29, 95% CI: 1.21-1.39, and women with asthma more often needed assisted reproduction aRR = 1.34 95% CI: 1.18-1.52. The risk of suffering a pregnancy loss was higher, aRR = 1.21, 95% CI: 1.15-1.28, and induced abortions were more common, aRR = 1.15, 95% CI: 1.11-1.20, among women with asthma. LIMITATIONS, REASONS FOR CAUTION: The study was an observational study based on healthcare visits and lacked detailed anthropometric data, thus residual confounding cannot be excluded. Only women with a healthcare visit for a reproductive outcome were included, which cannot be translated into pregnancy intention. A misclassification, presumed to be non-differential, may arise from an incorrect or missing diagnosis of asthma or female infertility, biasing the results towards the null. WIDER IMPLICATIONS OF THE FINDINGS: This study points towards reproductive dysfunction associated with asthma, specifically in regards to the ability to maintain a pregnancy and the risk of needing medically assisted reproduction following clinical infertility, but reassuringly the chance of subsequently giving birth was not lower for these women. STUDY FUNDING/COMPETING INTEREST(S): This article is part of the ReproUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and Ferring Pharmaceuticals. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Commentary on two recently published formal guidelines on management of "mosaic" embryos after preimplantation genetic testing for aneuploidy (PGT-A).

Two professional societies recently published opinions on the clinical management of "mosaic" results from preimplantation genetic testing for aneuploidy (PGT-A) in human blastocyst-stage embryos in associations with in vitro fertilization (IVF). We here point out three principal shortcomings: (i) Though a most recent societal opinion states that it should not be understood as an endorsement of the use of PGT-A, any discussion of how PGT-A should be clinically interpreted for all practical purposes does offer such an endorsement. (ii) The same guideline derived much of its opinion from a preceding guidance in favor of utilization of PGT-A that did not follow even minimal professional requirements for establishment of practice guidelines. (iii) Published guidelines on so-called "mosaic" embryos from both societies contradict basic biological characteristics of human preimplantation-stage embryos. They, furthermore, are clinically unvalidated and interpret results of a test, increasingly seen as harmful to IVF outcomes for many infertile women. Qualified professional organizations, therefore, should finally offer transparent guidelines about the utilization of PGT-A in association with IVF in general.

GM-CSF does not rescue poor-quality embryos: secondary analysis of a randomized controlled trial.

PURPOSE: To evaluate implantation potential of cleavage-stage embryos cultured in medium containing 2 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) versus control medium, according to embryo morphological quality and then transferred on day 3. METHODS: Explorative secondary data analysis of a multicenter, randomized, placebo-controlled, double-blinded prospective study of 1149 couples with embryo transfer after IVF/ICSI. This analysis includes a subgroup of 422 subjects with either single-embryo transfer (SET, N = 286) or double-embryo transfer of two embryos with equivalent morphological quality (DET, N = 136). Implantation rate and live birth rate were assessed according to category of morphological embryo quality on day 3. RESULTS: Culture with GM-CSF did not increase the implantation rate for embryos classified as poor quality. A trend towards greater benefit of GM-CSF on implantation and survival until live birth for top-quality embryos (TQEs) compared with poor-quality embryos was observed, although not statistically significant. For TQEs, the percentage of transferred embryos resulting in a live born baby was: 40.9 ± 5.3% (GM-CSF) versus 30.5 ± 4.6% (control) (P = 0.24; odds ratio [OR] 1.43, 95% confidence interval [CI] 0.79-2.59), and for embryos with less than 6 cells at day 3 this same rate was: 7.4 ± 3.3% (GM-CSF) versus 12.0 ± 4.0% (control) (P = 0.26; OR 0.53, 95% CI 0.17-1.61). CONCLUSION: This exploratory analysis is consistent with GM-CSF protecting morphologically normal embryos from culture-induced stress and does not support an effect of GM-CSF in rescuing poor-quality embryos. ClinicalTrials.gov identifier: NCT00565747.

Viable acrosome-intact human spermatozoa in the ejaculate as a marker of semen quality and fertility status.

STUDY QUESTION: Is it possible, in an unbiased and clinical relevant way, to determine the number of viable acrosome-intact human spermatozoa in ejaculates and to use this as a measure of fertility chances? SUMMARY ANSWER: Image cytometry enables easy and unbiased quantification of viable acrosome-intact spermatozoa and it correlates with semen quality and fertility status. WHAT IS KNOWN ALREADY: The presence of the acrosome and its ability to respond to physiological inducers (e.g. progesterone) in the female reproductive tract at the appropriate time and place is required for fertilization. However, the available assays are labor intensive and therefore not used clinically. STUDY DESIGN, SIZE, DURATION: Washed semen samples and capacitated swim-up fractions from volunteers were used to develop the assay. Subsequently washed ejaculates from patients in fertility treatment (n = 156), proven fertile men (n = 54) and volunteers (n = 10) were assessed to evaluate the number of acrosome-intact spermatozoa in the ejaculate (acrosomal status) and compared to other semen parameters, fertility status, fertility treatments and pregnancy rates. PARTICIPANTS/MATERIALS, SETTING, METHODS: Image cytometry was used to assess the fluorescence intensity of Pisum sativum agglutinin and Propidium iodide. MAIN RESULTS AND THE ROLE OF CHANCE: The assay was validated by inducing the acrosome reaction in swim-up-purified and capacitated spermatozoa with progesterone and ionomycin, and in repeated acrosomal status measurements of washed ejaculates a small coefficient of variation (3.7%) was observed. Men with poor semen quality had fewer viable acrosome-intact spermatozoa in the ejaculate (P = 0.0012; median 32.6% vs. 49.3%). A large proportion (44%) of normozoospermic men from infertile couples had less than the observed median fraction (46%) of viable acrosome-intact spermatozoa in the ejaculate. Furthermore, the total number of viable acrosome-intact spermatozoa was significantly lower among men with male factor infertility compared to fertile men (median 35 vs. 97 mill, P = 1 × 10-7). Men from couples going through one or more ICSI cycles had significant fewer viable acrosome-intact spermatozoa than men from couples who only underwent IUI (P = 0.002; 44.4% vs. 62.0%) and the fraction of viable acrosome-intact spermatozoa appeared better than classical semen parameters in classifying whether or not couples needed ICSI. A positive, although non-significant, tendency toward ongoing pregnancy with an increasing number of viable acrosome-intact spermatozoa was observed (P = 0.2). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Even larger cohorts of infertile couples are needed to substantiate the clinical application of the assay in regard to estimation of fertility potential of an individual. WIDER IMPLICATIONS OF THE FINDINGS: The presented assay makes it possible to measure the number of acrosome competent spermatozoa in an ejaculate in a standardized manner and hence may serve as a new biomarker for male fertility. Few spermatozoa in an ejaculate are acrosome competent and it might be a valuable measure when evaluating male reproductive function. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Innovation Fund Denmark. M.G. and S.K. work at ChemoMetec, which produces the image cytometer used in the study, M.G. hold shares in the company. The other authors have no conflict of interest.

Costs of medically assisted reproduction treatment at specialized fertility clinics in the Danish public health care system: results from a 5-year follow-up cohort study.

OBJECTIVE: To examine the costs to the public health care system of couples in medically assisted reproduction. DESIGN: Longitudinal cohort study of infertile couples initiating medically assisted reproduction treatment. SETTING: Specialized public fertility clinics in Denmark. SAMPLE: Seven hundred and thirty-nine couples having no child at study entry and with data on kind of treatment and live birth (yes/no) for each treatment attempt at the specialized public fertility clinic. METHODS: Treatment data for medically assisted reproduction attempts conducted at the public fertility clinics were abstracted from medical records. Flow diagrams were drawn for different standard treatment cycles and direct costs at each stage in the flow charts were measured and valued by a bottom-up procedure. Indirect costs were distributed to each treatment cycle on the basis of number of visits as basis. Costs were adjusted to 2012 prices using a constructed medical price index. MAIN OUTCOME MEASURES: Live birth, costs. RESULTS: Total costs per live birth in 2012 prices were estimated to 10,755€. Costs per treated couple - irrespective of whether the treatment was terminated by a live birth or not - were estimated at 6607€. Costs per live birth of women <35 years at treatment initiation were 9338€ and 15,040€ for women ≥35 years. CONCLUSION: The public costs for live births after conception with medically assisted reproduction treatment are relatively modest. The results can be generalized to public fertility treatment in Denmark and to other public treatment settings with similar limitations in numbers of public treatment cycles offered.

The prevalence of late-follicular phase progesterone elevation and impact on the ongoing pregnancy rate after fresh and frozen blastocyst transfer. Sub-study of an RCT.

The effect of late-follicular phase progesterone elevation (LFPE) during ovarian stimulation on reproductive outcomes in ART treatment remains controversial, but recent studies indicate lower pregnancy rates with rising progesterone levels. This study aims to investigate the prevalence of late-follicular phase progesterone elevation (LFPE) and possible impact on ongoing pregnancy rate after fresh or frozen blastocyst transfer in a sub-study setting of a randomised controlled trial. A total of 288 women were included (n=137 and n=151 in the fresh transfer and freeze-all group, respectively). Among these 11(3.8%) had a progesterone level ≥1.5 ng/ml, and 20(6.9%) had a progesterone level ≥1.2 ng/ml on trigger day. Spline regression analysis showed no significant effect of late follicular phase progesterone levels on ongoing pregnancy. In the multivariate regression analysis (n = 312) only age, but not progesterone level on trigger day was significantly associated with ongoing pregnancy. In conclusion, in a clinical setting with moderate gonadotrophin stimulation and well-defined trigger and fresh transfer cancellation criteria, the prevalence of women with LFPE ≥1.5 ng/ml was low and did not indicate the clinical value of routine measurement of progesterone in the late follicular phase.

Association between blastocyst morphology and outcome of single-blastocyst transfer.

The aim of this study was to assess the ability of three individual blastocyst morphology parameters - expansion and hatching (EH) stage, inner cell mass (ICM) grade and trophectoderm grade - to predict outcome of a cycle with single-blastocyst transfer. The study was a secondary analysis of data prospectively collected in a large multicentre trial. A total of 618 intracytoplasmic sperm injection patients undergoing ovarian stimulation in a gonadotrophin-releasing hormone antagonist cycle with compulsory single-blastocyst transfer on day 5 were included. In the simple logistic regression analysis, all three blastocyst morphology parameters were statistically significantly (P<0.005 for each) associated with positive human chorionic gonadotrophin, clinical and ongoing pregnancy rates and live birth rates, while only the ICM grade was significantly (P=0.033) associated with early pregnancy loss rate. Blastocyst EH stage was the only significant predictor of live birth (P=0.002) in the multiple logistic regression. In conclusion, although all three blastocyst morphology parameters were related to treatment outcome of fresh single-blastocyst cycles, selection of high-quality blastocysts for transfer should consider first the EH stage. Transfer of a blastocyst with ICM grade A may reduce the risk of early pregnancy loss. Choosing the embryo(s) with the best implantation potential is essential for securing each couple the highest chance of achieving pregnancy after assisted reproduction. The selection of embryo(s) for transfer at the blastocyst stage is based on morphology parameters of expansion and hatching stage, inner cell mass grade and trophectoderm grade. The aim of this study was to assess the relative impact of each parameter in predicting the probability of a successful outcome. The study was a secondary analysis of data prospectively collected in a large multicentre trial. A total of 618 patients who underwent single-blastocyst transfer on day 5 were included. Statistical analysis showed that all three blastocyst morphology parameters were significantly associated with positive human chorionic gonadotrophin (ßHCG), clinical and ongoing pregnancy rates and live birth rates. Only the inner cell mass grade was significantly associated with early pregnancy loss between the positive ßHCG test and confirmation of ongoing pregnancy 10-11weeks after transfer. The expansion and hatching stage was the only significant predictor of live birth in the multiple logistic regression analysis. In conclusion, although all three blastocyst morphology parameters were related to treatment outcome of fresh single-blastocyst cycles, selection of high-quality blastocysts for transfer should consider first the expansion and hatching stage. Transfer of a blastocyst with inner cell mass grade A may reduce the risk of early pregnancy loss.

Morphometric analysis of human embryos to predict developmental competence.

Morphometric and morphokinetic approaches toward embryo quality assessment have for many years been difficult due to technical limitations. Today, with improvements in laboratory techniques and subsequent quality, we have a better understanding of the morphometric and kinetics of embryo development. Fertility clinics are moving from "sensing" embryo quality to measuring embryo quality--and this is happening every day in fertility clinics all over the world. However, we cannot select for something that is not there. In daily clinical life it is almost never a question of selecting the optimal embryo, but rather choosing and prioritising between the available embryos. Data suggest that only approximately 5% of aspirated human oocytes have the competence to implant and develop into a child and that, in most treatment cycles, there is no oocyte capable of implanting. The most likely outcome is a negative pregnancy test, no matter what we choose in the laboratory. Still, both with the increasing complexity of infertile patients treated today and the important focus on reducing multiple pregnancies, it becomes increasingly important to improve our ability to predict the developmental competence of each embryo. This involves an improved understanding of the basic biology controlling early embryonic development and, over the years, many groups have tried to identify parameters reflecting embryonic competence.

The pros and cons of fertility awareness and information: a generational, Swedish perspective.

Being aware of factors that affect fertility can help people make informed decisions about their reproductive futures. To some, however, fertility information leads to worry and self-blame. In this paper, we explore how people from different generations discuss fertility and reproductive decision-making, along with their perceptions of fertility information. The study was conducted in southern Sweden with 26 focus-group discussions that included a total of 110 participants aged 17-90 years. The material was analysed thematically. Our results show that fertility knowledge and openness to talking about fertility problems have increased over generations. Participants who were assigned female at birth were more often concerned about their fertility than those who were not, and fertility concerns were transferred from mothers to daughters. While age-related fertility concerns had been uncommon in older generations, participants aged 25-40 often expressed these concerns. Young adults appreciated being knowledgeable about fertility but simultaneously expressed how fertility information could lead to distress. Our conclusion is that fertility information was best received by high-school students, and efforts to improve fertility education in schools are therefore recommended.

Expression of membrane fusion proteins in spermatozoa and total fertilisation failure during in vitro fertilisation.

BACKGROUND: Couples increasingly experience infertility and seek help from assisted reproductive techniques to become pregnant. However, 5%-15% of the couples that are selected for in vitro fertilisation (IVF) experience a total fertilisation failure (TFF), where no zygotes develop despite oocytes and semen parameters appear to be normal. We hypothesise that TFF during IVF could be related to improper membrane fusion of gametes. OBJECTIVE: To investigate the membrane integrity and fusion proteins in spermatozoa from men in couples experiencing TFF. MATERIALS AND METHODS: A total of 33 infertile couples, 17 of which experienced TFF during IVF and 16 matched control couples with normal IVF fertilisation rates, were selected and the men re-called to deliver an additional semen sample. Proteins involved in gamete membrane fusion on spermatozoa (IZUMO1, SPESP1 and Syncytin-1) as well as O-glycosylation patterns (Tn and GALNT3), were investigated by immunofluorescence. The DNA fragmentation index, acrosomal integrity and viability of spermatozoa were determined by flow and image cytometry. RESULTS: No significant changes in the expression of GALNT3, Tn and Syncytin-1 were observed between the TFF and control groups. The fraction of spermatozoa expressing SPESP1, the median IZUMO1 staining intensity, and the percentage of viable acrosome-intact spermatozoa were significantly lower in the TFF group compared to controls. Furthermore, following progesterone-induced acrosomal exocytosis, a significant difference in the fraction of spermatozoa expressing SPESP1 and the median IZUMO1 staining intensity were observed between the control and TFF group. DISCUSSION AND CONCLUSION: Our results indicate that acrosomal exocytosis, IZUMO1 and SPESP1 expression in spermatozoa could play a crucial role in achieving fertilisation during IVF. However, the size of our cohort was quite small, and our results need to be validated with quantitative methods in larger cohorts.

'Doing it in the right order': childless men's intentions regarding family formation.

In high-income countries, parental age at first birth has increased and this postponement increases the risk of involuntary childlessness or having fewer children than desired. This interview study was conducted in Denmark and Sweden among childless men (n = 29) in their last year of an education. The aim was to explore the role of individual and societal factors on fertility decision-making and men's reflections on barriers and enablers for earlier family formation. Data were analysed with thematic content analysis. Almost all participants wanted children in the future. Overall, there was a desire to follow the 'right chronology': get educated, having a stable relationship, employment and a good financial status before having children. While most men felt mature enough to have children, they were still not ready. Influences from within the inner social circle, societal expectations, the need for security and stability and being ready to give up freedom and individuality were factors that affected participants' preferred timing of parenthood. Most men did not have suggestions for how earlier family formation could be supported. Results suggest a gap between the ideal biological and ideal social age of family formation that may lead to unfulfilled parenthood aspirations.

A qualitative study on couples' attitudes and concerns regarding a freeze all strategy in ART treatment.

The freeze all strategy has become a promising alternative to fresh embryo transfer in fertility treatment almost eliminating late ovarian hyperstimulation syndrome (OHSS) in the segmented cycle. There is a lack of in-depth knowledge regarding patients' attitudes towards the freeze all strategy. The aim of this study was to explore the attitudes towards a freeze all strategy compared with fresh embryo transfer in assisted reproductive technology (ART) treatment among couples in a public health care setting. We conducted semi-structured qualitative interviews with ten couples already participants in a randomised controlled trial (RCT) and undergoing ART treatment. The couple's responses showed five themes: (i) Starting treatment provides needed relief; (ii) Treatment must be provided with humanity; (iii) Provision of information instigates positive attitudes towards treatment; (iv) Fresh treatment - 'The normal way'; and (v) Freeze all treatment - 'The new black'. When thorough information about treatment procedures and safety aspects regarding both the freeze all and fresh embryo transfer strategy is given prior to initiation of treatment, couples feel secure and content, regardless of which treatment strategy is finally applied. This qualitative study found that starting treatment could prompt longed-for relief, as professionals would now 'take over' and assist in meeting the couple's family building goals.

The long-term fiscal impact of funding cuts to Danish public fertility clinics.

This study evaluated the fiscal impact attributed to recent policy changes that limited funding to public fertility clinics in Denmark. Taking into consideration that introducing patient co-payments will influence the numbers of couples treated, the number of children born every year from assisted reproductive technology will be affected. To reflect the government perspective, the model assessed the average life course of a cohort of assisted-conception singletons taking into consideration age-specific, per-capita government transfers (e.g. education, health care, family allowances, education, pensions) and lifetime gross tax contributions to derive the discounted net tax contribution from assisted-conception singletons. An investment of €11,078 in a mother aged <40 to achieve an assisted-conception singleton was valued at €154,100 in cumulative discounted net tax revenue when the child reaches age 50. A reduction in the number of live births generated additional savings of €67-112 million due to reduced government transfers by age 25. However, by age 50, because of fewer children born and consequently fewer tax payers, a €74-123 million loss to government was estimated. The projected discounted net tax revenue attributed to assisted-conception children suggests that publicly funded treatment provides economic benefits to government over the lifetime of the conceived children. In January 2011, the Danish Parliament introduced a law that limited reimbursement to publicly funded fertility clinics in Denmark. Because reimbursement for fertility services can influence couples' ability to receive treatment, this will consequently result in fewer children being born each year. To inform the policy decision, this study assessed the fiscal consequences of the policy change on the government over many generations. The analytical framework discussed here estimates the net tax revenue of a cohort of assisted-conception children and the discounted net tax revenue that these children pay to the Danish government over their lifetime. The analysis illustrates that the government will save more costs than those directly related to public fertility services because fewer children are likely to be born and consequently to require government services (e.g. education, health care, family allowances). However, over time as the assisted-conception cohort matures and enters the work force. the reduced number of assisted-conception children, attributed to the funding cuts, will negatively impact government accounts due to lost tax revenue. The policy analysis described here suggests that the economic impact of the fertility policy change is dependent on the time frame over which the analysis is considered. In the short term, it is possible to save on assisted reproduction treatment costs; however, taking into consideration the life course of the diminished size of the assisted-conception cohort, this will negatively influence government accounts in the future.

Preconditions to parenthood: changes over time and generations.

Reproductive decision-making and fertility patterns change with time and place, and are influenced by contemporary societal factors. In this paper, we have studied biosocial aspects of reproductive decision-making over time and generations in a Nordic setting. The aim was to explore intergenerational changes and influences on decision-making, especially regarding preconditions to first birth. Twenty-six focus group interviews were conducted in southern Sweden, including a total of 110 participants aged 17-90 years. The analysis of the interviews resulted in six themes: (i) 'Providing security - an intergenerational precondition'; (ii) 'A growing smorgasbord of choices and requirements'; (iii) 'Parenthood becoming a project'; (iv) 'Stretched out life stages'; (v) '(Im)possibilities to procreate'; and (vi) 'Intergenerational pronatalism'. Our findings reflect increasing expectations on what it means to be prepared for parenthood. Despite increasing awareness of the precariousness of romantic relationships, people still wish to build new families but try to be as prepared as possible for adverse events. The findings also show how increasing life expectancy and medical advancements have come to influence people's views on their reproductive timeline.

Fertility outcomes in women with pre-existing type 2 diabetes-a prospective cohort study.

OBJECTIVE: To study childbirth and the risk of miscarriage and infertility among women who have received a diagnosis of type 2 diabetes before the start of their reproductive journey. DESIGN: Register-based cohort study using the Skåne Healthcare Register SETTING: All healthcare visits for the whole population of the southernmost region in Sweden over the past 20 years PATIENT(S): All women who were aged 18-45 years between January 1, 1998 and December 31, 2019 and who received a clinical diagnosis of type 2 diabetes before their first childbirth, miscarriage, or infertility diagnosis (n = 230) were compared with a healthcare-seeking population of women without any type of diabetes, matched for calendar year and age (n = 179,434). INTERVENTION(S): None MAIN OUTCOME MEASURE(S): Childbirth, miscarriage, and infertility diagnosis RESULT(S): The birthrate was lower among women with type 2 diabetes (62.6% vs. 83.8%), and they were less likely to give birth (crude risk ratio [RR] = 0.73, 95% confidence interval [CI]: 0.66-0.81). They had a higher risk of experiencing a miscarriage (RR = 1.88, 95% CI: 1.50-2.36). The risk of infertility was increased (RR = 3.44, 95% CI: 2.88-4.10) as was the risk of having infertility and not giving birth (RR = 4.47, 95% CI: 3.44-5.82). All results remained the same after adjustment for polycystic ovary syndrome and obesity. CONCLUSION(S): Women with type 2 diabetes with onset before their reproductive journey were more often childless compared with women without diabetes and had a higher risk of experiencing both miscarriage and infertility. This patient group may be in need of targeted information regarding potential fertility issues as part of their clinical treatment.

Adverse obstetric and perinatal outcomes in 1,136 singleton pregnancies conceived after programmed frozen embryo transfer (FET) compared with natural cycle FET.

OBJECTIVE: To investigate whether obstetric and perinatal outcomes in pregnancies differ after different frozen embryo transfer (FET) protocols. DESIGN: Register-based cohort study. SETTING: Not applicable. PATIENT(S): All singleton deliveries after assisted reproductive technology in Denmark from 2006 to 2014. Data consisted of 1,136 deliveries after frozen in vitro fertilization. Frozen embryo transfer cycles were grouped by type of FET protocol: programmed FET (n = 357); modified natural cycle FET (n = 611); and true natural cycle FET (n = 168). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Obstetric outcomes (hypertensive disorders in pregnancy, preterm prelabor rupture of membranes, placenta previa, placental abruption, induction of labor, postpartum hemorrhage, and cesarean section) and perinatal outcomes (post-term birth, preterm birth, birth weight, small for gestational age, large for gestational age). RESULT(S): The risk of hypertensive disorders in pregnancy, postpartum hemorrhage, and cesarean section was significantly higher after programmed FET compared with natural cycle FET (modified natural cycle FET and true natural cycle FET). A higher risk of birth weight > 4,500 g was observed in the programmed FET group compared with natural cycle FET. CONCLUSION(S): This study shows that obstetric and perinatal outcomes are adversely affected in programmed FET cycles. Hence, when possible, an endometrial preparation with the creation of a corpus luteum should be considered. Properly sized randomized controlled trials of FET in programmed cycle versus natural cycle including perinatal outcomes are warranted in the future. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN11780826.

Serum ferritin level is inversely related to number of previous pregnancy losses in women with recurrent pregnancy loss.

OBJECTIVE: To study whether low serum ferritin (s-ferritin) levels are associated with recurrent pregnancy loss (RPL), and whether low s-ferritin predicts the risk of another pregnancy loss or the ability to conceive. DESIGN: Cohort study. SETTING: Fertility clinic at a university hospital. PATIENT(S): Eighty-four women referred to the RPL Unit and 153 women of reproductive age with no known fertility problem. s-Ferritin levels were measured in serum samples taken before pregnancy attempt. INTERVENTION: None. MAIN OUTCOME MEASURE(S): s-Ferritin levels were correlated to pregnancy history, ability to conceive, and time to conception during the first 2 years after sampling. Furthermore, s-ferritin levels were correlated to outcome of the first pregnancy after referral for RPL. RESULT(S): Women with RPL had lower s-ferritin than the comparison group, 39.9 µg/L versus 62.2 µg/L, and had a higher prevalence of low iron stores (s-ferritin <30 µg/L), 35.7% versus 13.7%. We found an inverse relationship between s-ferritin level and number of pregnancy losses before referral. We did not find s-ferritin level to be associated with ability to conceive or time to pregnancy in either group. Nor did s-ferritin level predict the risk of losing the first pregnancy after referral for RPL. CONCLUSION(S): The inverse relationship between s-ferritin levels and previous pregnancy losses suggests that low s-ferritin is associated with a more severe reproductive disturbance in women with RPL. Whether low s-ferritin is causally related to RPL and if such women could benefit from iron supplementation to achieve a live birth warrants further investigation.

Immediate versus postponed single blastocyst transfer in modified natural cycle frozen embryo transfer (mNC-FET): a study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Today, it is widespread practice to postpone frozen embryo transfer (FET) in a modified natural cycle (mNC) for at least one menstrual cycle after oocyte retrieval and failed fresh embryo transfer or freeze-all. The rationale behind this practice is the concern that suboptimal ovarian, endometrial or endocrinological conditions following ovarian stimulation may have a negative impact on endometrial receptivity and implantation. However, two recent systematic reviews and meta-analyses based on retrospective data did not support this practice. As unnecessary delay in time to transfer and pregnancy should be avoided, the aim of this study is to investigate if immediate single blastocyst transfer in mNC-FET is non-inferior to standard postponed single blastocyst transfer in mNC-FET in terms of live birth rate. METHODS AND ANALYSIS: Multicentre randomised controlled non-blinded trial including 464 normo-ovulatory women aged 18-40 years undergoing single blastocyst mNC-FET after a failed fresh or freeze-all cycle. Participants are randomised 1:1 to either FET in the first menstrual cycle following the stimulated cycle (immediate FET) or FET in the second or subsequent cycle following the stimulated cycle (postponed FET). The study is designed as a non-inferiority trial and primary analyses will be performed as intention to treat and per protocol. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Scientific Ethical Committee of the Capital Region of Denmark (J-nr.: H-19086300). Data will be handled according to Danish law on personal data protection in accordance with the general data protection regulation. Participants will complete written consent forms regarding participation in the study and storage of blood samples in a biobank for future research. The study will be monitored by a Good Clinical Practice (GCP)-trained study nurse not otherwise involved in the study. The results of this study will be disseminated by publication in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04748874; Pre-results.