Parenthood among men diagnosed with cancer in childhood and early adulthood: trends over time in a Danish national cohort.

STUDY QUESTION: Is the rate of fatherhood among men diagnosed with cancer in childhood and early adulthood different from men without cancer, and, if so, have the differences changed over time? SUMMARY ANSWER: Men diagnosed with cancer have had significantly reduced rates of fatherhood compared with undiagnosed men; however, the rates of fatherhood among the cancer survivors have increased markedly over time. WHAT IS KNOWN ALREADY: The number of children and young adolescents who survive cancer has steadily increased over recent decades, with a current 5-year survival rate of approximately 80%. Consequently, life circumstances after cancer have gained increasing importance, including the desire among survivors to have children and a family. ARTs to aid reproduction among cancer survivors have been developed, and fertility preservation is increasingly a topic being discussed before undergoing cancer treatment. But the potential for fertility preservation differs dependent on age at diagnosis and type of cancer. Earlier studies have shown a decreased fertility rate among survivors of child and adolescent cancer compared to those diagnosed in early adulthood. STUDY DESIGN, SIZE, DURATION: This study is a national, register-based cohort study. Men diagnosed with cancer in childhood and early adulthood (<30 years of age) were registered in the Danish Cancer Register in 1978-2016 (n = 9353). According to the time of diagnosis, each cancer-diagnosed man was randomly matched with 150 undiagnosed men from the background population within the same birth year. The men were followed until having their first child, death, migration or the end of the study (31 December 2017) in medical registers and socio-demographic population registers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fatherhood among the boys and young men diagnosed with cancer were compared with the age-matched comparison group in all statistical analyses. Cancer diagnoses were categorised as central nervous system (CNS) cancers, haematological cancers or solid cancers. Analyses were stratified by age at diagnosis (0-9, 10-19, 20-29 years) and time of diagnosis (1978-1989, 1990-1999, 2000-2009, 2010-2016). Death was incorporated as a competing risk in all analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The study population consisted of 9353 boys and young men diagnosed with cancer between 1978 and 2016 and 1 386 493 men in the age-matched comparison group. Those surviving CNS cancer as young men had the lowest hazard ratio (HR) of fatherhood compared with the age-matched comparison group (HR 0.67, 95% CI 0.57-0.79), followed by survivors of haematological cancers (HR 0.90, 95% CI 0.81-1.01), while the highest chance of fatherhood was among survivors of solid cancers (HR 1.16, 95% CI 1.12-1.20) with a slightly increased HR compared with undiagnosed males. The HR of becoming a father increased over time. From the first decade to the last decade 30 years later, the HR of becoming a father increased for solid tumours (HR 0.78, 95% CI 0.73-0.83 to HR 1.08, 95% CI 0.95-1.22), haematological cancers (HR 0.64, 95% CI 0.53-0.79 to HR 0.97, 95% CI 0.73-1.30) and CNS cancers (HR 0.44, 95% CI 0.34-0.57 to HR 0.98, 95% CI 0.49-1.95) compared to the age-matched comparison group. Also, when compared with the age-matched comparison group, men diagnosed with cancer when aged 20-29 years were more likely became fathers over the time of the study (HR 0.80, 95% CI 0.74-0.86 to HR 1.08, 95% CI 0.96-1.22). LIMITATIONS, REASONS FOR CAUTION: The study was based on register data, and information was not available about the men's fertility potential, whether they had a desire to have children and whether it was possible for them to find a partner. Information about fertility preservation, e.g. sperm freezing, could also have provided additional insights. Furthermore, information about diagnosis and ART treatment would have been beneficial. WIDER IMPLICATIONS OF THE FINDINGS: Information and education of male patients diagnosed with cancer about fertility preservation options and their chances to create their own family is crucial. Reassuringly, time trends showed more men with a previous cancer diagnosis becoming fathers in recent years than in earlier years, reflecting that survival and fertility preservation have improved over time. STUDY FUNDING/COMPETING INTEREST(S): R.S. received a PhD grant from the Rosa Ebba Hansen Foundation and from the Health Foundation (J.nr. 15-B-0095). The funding for the establishment of the DANAC II Cohort was obtained from the Rosa Ebba Hansen Foundation. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Women's perceptions of fertility assessment and counselling 6 years after attending a Fertility Assessment and Counselling clinic in Denmark.

STUDY QUESTION: What are women's perceptions and experience of fertility assessment and counselling 6 years after attending a Fertility Assessment and Counselling (FAC) clinic in Denmark? SUMMARY ANSWER: Women viewed the personalized fertility knowledge and advice they received as important aids to decision-making and they felt the benefits outweighed the risks of receiving personalized fertility information. WHAT IS KNOWN ALREADY: Many young people wish to become parents in the future. However, research demonstrates there is a gap in women's and men's knowledge of fertility and suggests they may be making fertility decisions based on inaccurate information. Experts have called for the development of interventions to increase fertility awareness so that men and women can make informed fertility decisions and achieve their family-building goals. Since 2011, the FAC clinic in Copenhagen, Denmark has provided personalized fertility assessment and guidance based on clinical examination and evaluation of individual risk factors. Available qualitative research showed that attending the FAC clinic increased fertility awareness and knowledge and was experienced as a catalyst for change (e.g. starting to conceive, pursuing fertility treatment, ending a relationship) in women 1-year post-consultation. STUDY DESIGN SIZE DURATION: The study was a 6-year follow-up qualitative study of 24 women who attended the FAC clinic between January and June 2012. All women were interviewed during a 2-month period from February to March 2018 at Rigshospitalet, their home or office, in Copenhagen, Denmark. Interviews were held in English and ranged between 60 and 94 min (mean 73 min). PARTICIPANTS/MATERIALS SETTING METHODS: Invitations to participate in an interview-based follow-up study were sent to 141 women who attended the FAC clinic in 2012. In total, 95 women read the invitation, 35 confirmed interest in participating and 16 declined to participate. Twenty-five interviews were booked and 24 interviews held. Interviews followed a semi-structured format regarding reasons for attending the FAC clinic, if/how their needs were met, and perceptions of fertility assessment and counselling. Data were analysed using thematic analysis. MAIN RESULTS AND THE ROLE OF CHANCE: At the follow-up interview, women were on average 39.5 years old. Ten were currently single or dating and 14 were married/cohabiting. All were childless when they attended the FAC clinic. At the follow-up interview, 21 women were parents (14 women with one child; 6 with two children; 1 with three children) and the remaining three women intended to have children in the future. The most common reason for originally attending the FAC clinic was to determine how long they could delay childbearing. Most of the women now believed their needs for attending had been met. Those who were dissatisfied cited a desire for more exact ('concrete') information as to their remaining years of fertility, although acknowledged that this was likely not realistic. Women stated that they had felt reassured as to their fertility status after attending the FAC clinic whilst receiving the message that they could not delay childbearing 'too long'. Women viewed personalized fertility knowledge as an important aid to decision-making but cautioned about developing a false sense of security about their fertility and chance of conceiving in the future based on the results. Although women were generally satisfied with their experience, they wished for more time to discuss options and to receive additional guidance after their initial meeting at the FAC clinic. LIMITATIONS REASONS FOR CAUTION: Participants were from a group of Danish women attending the FAC clinic and interviews were conducted in English, which means they are not representative of all reproductive-aged women. Nevertheless, the study group included a broad spectrum of women who achieved parenthood through different means (heterosexual/lesbian relationship, single parent with donor, co-parent) with various family sizes, and women who were currently childless. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides support for an individualized approach to fertility education, assessment and counselling provided at a time when the information is relevant to the individual and their current fertility decision-making. The findings suggest that although satisfied with their visit to the FAC clinic, the women wished for more information and guidance after this visit, suggesting that the current intervention may need to be expanded or new interventions developed to meet these additional needs. STUDY FUNDING/COMPETING INTERESTS: E.K. was funded by an ESHRE Travel/Training grant by ReproUnion, co-financed by the European Union, Interreg V OKS. J.B. reports that the risk evaluation form used at the Fertility Assessment Clinic was inspired by the Fertility Status Awareness Tool FertiSTAT that was developed at Cardiff University for self-assessment of reproductive risk. J.B. also reports personal fees from Merck KGaA, Merck AB, Theramex, Ferring Pharmaceuticals A/S and a research grant from Merck Serono Ltd outside the submitted work. A.N.A. has received personal fees from both Merck Pharmaceuticals and Ferring and grants from Roche Diagnostics outside the submitted work. The other authors report no conflicts of interest.

Recurrent pregnancy loss: couples' perspectives on their need for treatment, support and follow up.

STUDY QUESTION: What do couples referred to or attending a recurrent pregnancy loss (RPL) clinic believe they need in terms of treatment, support and follow up? SUMMARY ANSWER: Men and women wish for more information, earlier access to treatment, support and follow up that is sensitive to their history of pregnancy loss (PL), includes both members of the couple, and acknowledges the psychological impact of RPL. WHAT IS KNOWN ALREADY: Previous research has highlighted women's dissatisfaction with medical care provided post-PL and their desire for medical professionals to have increased awareness about PL and recognition of the psychological impact of PL. Less is known about the needs of the male partner, the needs of those experiencing RPL and whether the needs differ during different reproductive stages. STUDY DESIGN, SIZE, DURATION: Over a 2-month period in 2017-2018, 13 couples who were referred to the national RPL program in Copenhagen, Denmark were qualitatively interviewed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria were heterosexual couples with at least three consecutive PLs before 12 weeks' gestation with no children or one child prior to the PLs, not currently pregnant, and willing to be interviewed in English. Couples were interviewed together in a semi-structured format. Data were analyzed using thematic analysis. Invitations (n = 30) were sent to couples recently referred to the RPL program who indicated an interest in participating and 17 couples contacted the interviewer to schedule an interview. Due to cancellations, 15 interviews were held. Data from 13 interviews that met the study criteria were used for the current analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The participants had experienced a median of three PLs (range 3-6). Both men and women described the cumulative effect of RPL with an increase in pressure and exhaustion by the third and subsequent losses. Inclusion of the male partner in consultations and treatment was seen as important. Men felt pressured to remain positive and support their partners despite their own feelings of loss. The findings showed that couples desired reliable and accurate information about RPL. They wished for recognition from the medical community that RPL has a significant psychological impact, and stressed that effective treatment should include both members of the couple, with attention to both physical and psychological aspects of the RPL and should be tailored to their current reproductive stage, in order to help them cope with the negative impact of RPL and the anxiety associated with conception and another pregnancy. LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected thus findings cannot be generalized to all couples with RPL. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study addressing the needs of the female and male partners in couples suffering from RPL. The findings highlight a disconnect between couples' perceived needs and their experience of medical care after RPL. This may be partly due to a discrepancy in couples' and medical professionals' perceptions of the PLs. The findings highlight that medical professionals need to take a holistic and couple-focused approach in their treatment of RPL and include attention to the psychological impact and cumulative effect of the multiple PLs on the couple. The results underscore the need for informational resources and psychological support for couples experiencing RPL, tailored to their reproductive stage. STUDY FUNDING/COMPETING INTEREST(S): EK was funded by a Travel/Training Fellowship from ReproUnion, co-financed by the European Union, Interreg V ÖKS. No other competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.

Attitudes towards family formation among men attending fertility counselling.

Men and women are increasingly postponing childbearing until an age where fertility has decreased, meaning that they might have difficulties in achieving their desired family size. This study explored childless men's attitudes towards family formation. Data were collected through semi-structured qualitative interviews with 21 men attending the Fertility Assessment and Counselling Clinic in Copenhagen or Horsens, Denmark. Data were analysed using content analysis. The men envisioned a nuclear family with their own biological children, but they experienced doubts and ambivalence about parenthood and feeling 'ready'. Their lack of readiness was linked to their awareness of the sacrifices and costs involved with parenthood, and their belief that they could safely delay parenthood. The men did not consider that they may be unable to have their own biological children. This study highlights the importance of considering men's attitudes and preferences towards family formation when understanding couples' decision-making. Contrary to common understanding, the findings show that men are as concerned with the planning and timing of parenthood as women, but their knowledge of the age-related decline in fertility is poor. Men need to gain more awareness of the limitations of fertility and the impact of female and male age on the ability to achieve parenthood aspirations.

Family intentions and personal considerations on postponing childbearing in childless cohabiting and single women aged 35-43 seeking fertility assessment and counselling.

STUDY QUESTION: What characterizes childless women aged 35 years and above seeking fertility assessment and counselling in relation to their reproduction and are there significant differences between single and cohabiting women? SUMMARY ANSWER: Despite the women's advanced age and knowledge of the age-related decline in fecundity, 70% of the single women sought fertility assessment and counselling to gain knowledge regarding the possibility of postponing pregnancy. WHAT IS KNOWN ALREADY: Recent studies have indicated an increasing demand for ovarian reserve testing in women without any known fertility problem to obtain knowledge on their reproductive lifespan and pro-fertility advice. Women postpone their first pregnancy, and maternal age at first birth has increased in western societies over the past two to four decades. Postponed childbearing implies a higher rate of involuntary childlessness, smaller families than desired and declining fertility rates. STUDY DESIGN, SIZE, AND DURATION: Baseline data from a cross-sectional cohort study of 340 women aged 35-43 years examined at the Fertility Assessment and Counselling (FAC) Clinic at Copenhagen University Hospital from 2011 to 2014. The FAC Clinic was initiated to provide individual fertility assessment and counselling. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible women were childless and at least 35 years of age. All completed a web-based questionnaire before and after the consultation including socio-demographic, reproductive, medical, lifestyle and behavioural factors. Consultation by a fertility specialist included transvaginal ultrasound, full reproductive history and AMH measurement. MAIN RESULTS AND THE ROLE OF CHANCE: The study comprised 140 cohabiting and 200 single women. The majority (82%) were well-educated and in employment. Their mean age was 37.4 years. Nonetheless, the main reasons for attending were to obtain knowledge regarding the possibility of postponing pregnancy (63%) and a concern about their fecundity (52%). The majority in both groups (60%) wished for two or more children. The women listed their ideal age at birth of first child and last child as 33 (±4.7) years and 39 (±3.5) years, respectively. Of the single women, 70% would accept use of sperm donation compared with 25% of the cohabiting women (P < 0.001). In general, 45% considered oocyte vitrification for social reasons, yet only 15% were positive towards oocyte donation. The two groups were comparable regarding lifestyle factors, number of previous sexual partners, pregnancies, and ovarian reserve parameters. LIMITATIONS, REASONS FOR CAUTION: The women in the present study were conscious of the risk of infertility with increasing age and attended the FAC Clinic due to a concern about their remaining reproductive lifespan, which in combination with their high educational level could impair the generalizability to the background population. WIDER IMPLICATIONS OF THE FINDINGS: The results indicate that in general women overestimate their own reproductive capacity and underestimate the risk of future childlessness with the continuous postponement of pregnancies.

Ovarian reserve assessment in users of oral contraception seeking fertility advice on their reproductive lifespan.

STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume were found to be significantly decreased by 19% (95% CI 9.1-29.3%), 18% (95% CI 11.2-24.8%) and 50% (95% CI 45.1-53.7%) among OC users compared with non-users. WHAT IS KNOWN ALREADY: AMH and AFC have proved to be reliable predictors of ovarian ageing. In women, AMH declines with age and data suggest a relationship with remaining reproductive lifespan and age at menopause. OC may alter parameters related to ovarian reserve assessment but the extent of the reduction is uncertain. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 887 women aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women were examined on a random cycle day by a fertility specialist. Consultation included; transvaginal ultrasound (AFC, ovarian volume, pathology), a full reproductive history and AMH measurement. Women were grouped into non-users and users of OC (all combinations of estrogen-progestin products and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19% lower (95% CI 9.1-29.3%), and AFC was 18% lower (95% CI 11.2-24.8%) in OC users compared with non-users. Comparison of AMH at values of <10 pmol/l OC was found to have a significant negative influence on AMH (OR 1.6, 95% CI 1.1; 2.4, P = 0.03). Furthermore, we found a significant decrease in antral follicles sized 5-7 mm (P < 0.001) and antral follicles sized 8-10 mm (P < 0.001) but an increase in antral follicles sized 2-4 mm (P = 0.008) among OC users. The two groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION: The study population comprised women attending the FAC Clinic. Recruitment was based on self-referral, which could imply a potential selection bias. Ovarian reserve was examined at a random cycle day. However, both AMH and AFC can be assessed independently of the menstrual cycle. The accuracy in predicting residual reproductive lifespan is still needed in both users and non-users of OC. WIDER IMPLICATIONS OF THE FINDINGS: OC has a major impact on the ovarian volume, and a moderate impact on AFC and AMH with a shift towards the smaller sized antral follicle subclasses. The most evident reduction occurs in the antral follicles of 5-7 and 8-10 mm with the highest number of AMH secreting granulosa cells. It is essential to be aware of the impact of OC use on ovarian reserve parameters when guiding OC users on their fertility status and reproductive lifespan. STUDY FUNDING/COMPETING INTERESTS: The FAC Clinic was established in 2011 as part of the ReproHigh collaboration. This study received funding through the Capital Region Research Fund and by EU-regional funding. There are no competing interests. TRIAL REGISTRATION NUMBER: The biobank connected to FAC Clinic is approved by the Scientific Ethical Committee (H-1-2011-081).