Intravaginal exposure to seminal plasma after ovum pick-up does not increase live birth rates after in vitro fertilization or intracytoplasmic sperm injection treatment: a double-blind, placebo-controlled randomized trial.

OBJECTIVE: To detect whether intravaginal exposure to prepared seminal plasma led to an absolute increase in live birth rate (LBR) after in vitro fertilization (IVF) by 10% compared with placebo. It has been suggested that intravaginal deposition of seminal plasma after ovum pick-up (OPU) for IVF treatment, increases pregnancy and LBRs. DESIGN: Double-blind, placebo-controlled prospective study. An outcome assessment was made before the type of intervention was unblinded. The outcome data were analyzed according to an intention-to-treat protocol. SETTING: University Hospital. PATIENTS: Couples scheduled for an IVF treatment cycle: in total, 792 couples (393 in the seminal plasma group and 399 in the control group) were recruited over a 5-year period of inclusion in a single-center setting. INTERVENTION: On the day of OPU, the couples were randomized into groups receiving either vaginal deposition of prepared seminal plasma from the partner or saline. Both participants and the physician were blind to the grouping. MAIN OUTCOME MEASURES: The primary outcome was a live birth (LB). The secondary outcomes were a positive pregnancy test, defined as human chorionic gonadotropin identified in urine 3 weeks after OPU , and clinical pregnancy, defined as an intrauterine viable pregnancy assessed using transvaginal sonography after 5-7 weeks. RESULTS: In the index group, 35.4% had a positive pregnancy test (relative risk [RR],0.93; 95% confidence interval {CI} 0.78-1.10), 28.8% had a clinical pregnancy (RR 1.00, 95% CI 0.97-1.03), and 26.5% had a LB (RR 0.86; 95% CI 0.70-1.07), adjusted for day of transfer, female age, and number of fertilized oocytes. Corresponding rates in the control group were 37.3%, 33.6%, and 29.8%. No statistically significant differences regarding outcomes between the two intervention groups were found. CONCLUSION: Prepared seminal plasma applied in the vagina directly after OPU did not increase the rates of LB or clinical pregnancies. The importance of immunological factors to allow the implantation of an embryo is not questioned, but no improvement in the LBRs in IVF treatment by introducing the male partner's prepared seminal plasma after OPU could be found. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, ID NCT02716753. Registration date 17 March, 2016, first enrollment November, 2016, completed March, 2023.

Long-term follow-up of mental health and satisfaction in a Swedish sample of sperm and egg donors after open-identity donation.

RESEARCH QUESTION: How is the mental health of open-identity gamete donors and their satisfaction with their contributions 14-17 years after acceptance as a donor? DESIGN: The Swedish Study on Gamete Donation is a longitudinal study comprising women and men who were accepted as donors at seven Swedish university clinics between 2005 and 2008. The latest (fifth) follow-up included 215 open-identity donors (response rate 87%): 123 oocyte donors and 92 sperm donors. The donors answered a questionnaire regarding their perceptions, experiences and expectations after gamete donation 14-17 years previously. RESULTS: The donors were satisfied with the experience of donating, and no differences were detected between sperm and oocyte donors. Oocyte donors were more than twice as likely to feel that family and friends were proud of their donation compared with sperm donors (51% versus 23%, P < 0.001). In total, six donors regretted their donation: four oocyte donors and two sperm donors. Sperm donors were more frequently satisfied with the financial compensation compared with oocyte donors (P = 0.005). No difference in the development of symptoms of anxiety or depression was detected 14-17 years post-donation. CONCLUSION: Long-term follow-up studies on donors are important for recruiting donors, and for recipients and the children who will be conceived with donated gametes. The results from the current study indicate that donors, generally, have good mental health and do not regret their decision to donate gametes. These findings are reassuring for all parties involved.

Maternal advanced age, single parenthood, and ART increase the risk of child morbidity up to five years of age.

BACKGROUND: Advanced maternal age, single status and use of assisted reproductive technology (ART) are increasing in mothers in high-income countries, and all are known risk factors for negative obstetric outcomes. Less is known about their long-term consequences for childhood morbidity. Thus, the aim of this study was to investigate morbidity up to five years of age, in the children of older, single, and/or ART-treated mothers. METHODS: A cross-sectional using Swedish registers was performed comprising 23 772 children. The prevalence of diagnosis and the number of hospital visits for specialist care, were compared and analyzed in relation to maternal age at childbirth, maternal civil status, and mode of conception. The odds ratio for specialized care within each ICD-chapter were estimated using single and multiple logistic regression. RESULTS: Children born to single mothers and children conceived using ART had significantly more outpatient visits for specialist care and significantly more diagnoses compared to children with married/cohabiting mothers, and spontaneously conceived children. Children born to mothers of advanced maternal age (≥40) had fewer in- and outpatient visits. However, they were significantly more often diagnosed within ICD-chapters XVI, XVII i.e., they experienced more morbidity in the neonatal period. CONCLUSION: The results indicate that children born to single mothers and children of ART-treated mothers have a higher morbidity and consume more specialist care than children of married/cohabiting and spontaneously pregnant mothers. We conclude that the use of ART, maternal single status and advanced maternal age are risk factors of importance to consider in pediatric care and when counseling women who are considering ART treatment.

Men born small for gestational age or with low birth weight do not improve their rate of reproduction over time: a Swedish population-based study.

OBJECTIVE: To investigate whether the reduced reproductive rate among men born small for gestational age (SGA) or with low birth weight (LBW) is present after up to 44 years of follow-up. DESIGN: Population-based register study. SETTING: National registers in Sweden. PATIENT(S): All men born in Sweden between 1973 and 1993 (n = 1,045,167) followed up to 2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Registered fatherhood, infertility diagnoses, and fertility treatments obtained from registers up to 2018 RESULT(S): Men born SGA or with LBW have a lower chance of becoming fathers than men born with normal birth characteristics: hazard ratio (95% confidence interval) 0.91 (0.90-0.92) and 0.88 (0.86-0.90), respectively. The reduction in reproductive rate is more evident after a longer follow-up time. Men born SGA were more likely to receive a diagnosis of infertility. Sperm donation and intracytoplasmic sperm injection were more often used in men born SGA, further strengthening the hypothesis of an association between birth characteristics and male infertility. CONCLUSION(S): Men born SGA or with LBW have a lower chance of becoming fathers, but the reduction in fertility is smaller for the younger cohort. Further studies are needed to determine if this difference is maintained.

Birth characteristics in men with infertility.

RESEARCH QUESTION: Are low birth weight, prematurity, being born small for gestational age, or both, associated with a higher risk of male factor infertility in adulthood? DESIGN: Retrospective study of a clinical sample of 892 men, diagnosed with an infertility factor (male, female, combined or unexplained) together with their female partner at a University Hospital clinic in Sweden between 2005 and 2010. Data on birth weight and gestational age at birth were retrieved from the Swedish Medical Birth Register. The distribution of non-optimal birth characteristics in relation to infertility factor was described. A control group was created consisting of two men for each index man, born in Sweden in the same year as each index men, as well as a reference group consisting of all men born in Sweden the same years. RESULTS: The likelihood of having been born small for gestational age was almost fivefold higher in men with male factor infertility than in men with unexplained infertility (OR 4.84, 95% CI 1.32 to 17.80). Men with male factor infertility were more often born with non-optimal birth characteristics than the control group (14.8% versus 8.5%; P = 0.010) and the reference group (14.8% versus 11.4%; P < 0.001). Men with azoospermia were more often born with non-optimal birth characteristics, compared with men without azoospermia (21.3% versus 12.1%; P = 0.038). CONCLUSIONS: The results suggest an association between intrauterine growth restriction and male factor infertility in adulthood.

Mothers who have given birth at an advanced age - health status before and after childbirth.

Women postpone childbirth to an age when morbidity is higher and fertility has decreased and yet the knowledge of mothers' morbidity related to age remains scarce. Swedish national register data from the Medical Birth Register and National Patient Register was used to investigate the incidence of diseases listed in the International Classification of Diseases, version 10 (ICD-10) in women who gave birth 2007-8. The index group consisted of women 40 years of age or older (n = 8 203) were compared to a control group of women, younger than 40 years (n = 15 569) at childbirth. The period studied was five years before childbirth to five years after. The main outcome measures were incidence of disease diagnosed in specialized hospital care. Demographical data and use of assisted reproduction (ART) were adjusted for. The results showed that older women were more likely to be single; less frequently used tobacco; were educated on a higher level; had a higher BMI and more often had used ART to become pregnant. The older women showed a higher morbidity rate. In the diagnostic groups: Neoplasms, Blood and immune system, Eye and adnexa, Ear and mastoid, Circulatory, Digestive, Skin and subcutaneous tissue, Musculoskeletal and connective tissue, and Genitourinary. The results add to the body of knowledge of a number of specific risks faced by older mothers and may be used to identify preventive actions concerning fertility and morbidity both before and after childbirth.

Being born preterm or with low weight implies a risk of infertility and premature loss of ovarian function; a national register study.

Background: Being born with non-optimal birth characteristics has several long-term consequences on health in general but also for the individual's reproductive pattern. In premature ovarian insufficiency (POI) the follicles are depleted or dysfunctional. This results in menopause before the age of 40, and for most of the affected women, it causes infertility. The objective of this study was to evaluate the potential effects of being born with non-optimal birth characteristics on the risk of developing POI.Methods: This population-based cohort register study included all women born in Sweden between 1973 and 1993 who were followed until the end of 2012 (age at the end of follow-up ranged between 39 and 59). Women diagnosed with POI were compared with women without this diagnosis with respect to being born small for gestational age, preterm, or with low birth weight. Data on birth characteristics and diagnosis of POI were collected from national registers.Results: A total of 1,033,878 women were included. Being born small for gestational age was associated with a slightly increased odds ratio of POI with 10%. Preterm birth and low birth weight were associated with somewhat increased ORs of POI after exclusion of those born small for gestational age. Similarly, being born preterm or with a low birth weight was also found to be associated with POI to the same extent.Conclusions: Being born with non-optimal birth characteristics may increase the risk of premature ovarian insufficiency.

Efficacy and safety of controlled ovarian stimulation using GnRH antagonist protocols for emergency fertility preservation in young women with breast cancer-a prospective nationwide Swedish multicenter study.

STUDY QUESTION: How efficacious and safe are the current approaches to controlled ovarian stimulation (COS) aimed at fertility preservation (FP) in women with breast cancer (BC)? SUMMARY ANSWER: In women with BC undergoing COS aiming at egg/embryo cryopreservation, letrozole-based protocols and those randomly started were equally effective compared with conventional COS, and the overall survival was similar between the women that proceeded to FP and those who did not. WHAT IS KNOWN ALREADY: Cryopreservation of oocytes and embryos is an established method for FP in women with BC. Recent improvements to COS protocols include concomitant use of letrozole, random-cycle start day of stimulation and the use of GnRHa for the egg maturation trigger. To date, limited sample size of the available studies has not allowed investigation of differences in the efficacy of the different approaches to COS for FP in this patient population. STUDY DESIGN, SIZE, DURATION: A prospective multicenter study with national coverage including 610 women with BC counseled between 1 January 1995 and 30 June 2017 at six Swedish FP regional programs. PARTICIPANTS/MATERIALS, SETTING, METHODS: After counseling, 401 women elected to undergo COS. Treatments differed in the use or not of concomitant letrozole, a conventional or random-cycle day COS initiation and the use of hCG versus GnRHa trigger for oocyte maturation. Numbers of cryopreserved oocytes and embryos were defined as primary outcome. Pregnancy attempts, reproductive outcomes and long-term survival, investigated by the linking of individuals of the cohort to the total population register of the Swedish Tax Agency (up to 25 November 2018), were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Using letrozole or not resulted in similar numbers of oocytes and embryos cryopreserved (meanoocytes = 9.7 versus 10 and meanembryos 4.0 versus 5.3, respectively), similar to COS with random versus conventional start (meanoocytes 9.0 versus 10.6 and meanembryos 4.8 versus 4.8). In COS with letrozole, a GnRHa trigger was associated with a higher number of oocytes retrieved (P < 0.05) and embryos cryopreserved (P < 0.005), compared with conventional hCG trigger. Of 99 women who returned to fertility clinics after cancer treatment, 32 proceeded to thawing of oocytes or embryos and 10 of them had live births. The all-cause survival between the women that underwent COS and those who did not was similar and did not differ between the two groups. LIMITATIONS, REASONS FOR CAUTION: Data on tumor characteristics and estrogen receptor (ER) status were not known for all women at the time of FP counseling and planning of COS, thus protocols with letrozole have been used for both estrogen-sensitive and non-estrogen-sensitive BC. For the same reason, subsequent adjustment for ERs in the BC or tumor characteristics as potential confounders were not performed as these parameters were not available and did not influence the provision of FP through COS. WIDER IMPLICATIONS OF THE FINDINGS: The results of our study support the premise that recently introduced potential improvements to COS protocols for FP in women with BC are efficacious and safe. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by research grants from the Swedish Cancer Society, the Stockholm County Council, the Percy Falk Stiftelsen, Radiumhemmets Forskningsfonder, The Swedish Breast Cancer Association and Karolinska Institutet to K.A.R.W. J.B. reports grants from Amgen, AstraZeneca, Pfizer, Roche, Sanofi-Aventis and Merck, outside the submitted work, and payment from UpToDate to Asklepios Medicine HB for a chapter on BC prediction and prognostication. All the other authors have no competing interests to report.

Human sperm displays rapid responses to diet.

The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.

Diagnostics of DNA fragmentation in human spermatozoa: Are sperm chromatin structure analysis and sperm chromatin dispersion tests (SCD-HaloSpermG2® ) comparable?

Men affected with idiopathic infertility often display basic spermiogramme values similar to fertile individuals, questioning the diagnostic impact of the World Health Organization (WHO) thresholds used. This study explored sperm DNA fragmentation in single ejaculates from 14 fertile donors and 42 patients with idiopathic infertility providing semen for assisted reproductive techniques in a university fertility clinic. Each ejaculate was simultaneously studied for sperm DNA fragmentation by the flow cytometer-based sperm chromatin structure analysis (SCSA) and the new light-microscopy-based sperm chromatin dispersion assay (SCD-HaloSpermG2® ), before and after sperm selection for in vitro fertilisation with a colloid discontinuous gradient. The WHO semen variables did not differ between groups, but DNA fragmentation after SCSA (DFI) or SCD (SDF) was significantly (p < 0.05) higher in patients (DFI: 40.2% ± 3.0 vs. SDF: 40.3% ± 1.4) than in fertile donors (DFI: 17.1% ± 2.1 vs. SDF: 20.9% ± 2.5). Sperm selection led to lower proportions of DNA-fragmented spermatozoa (DFI: 11.9 ± 1.7 vs. SCD: 10.0 ± 0.9, p < 0.05). The techniques output correlated highly and significantly (r2  = 0.82). DNA fragmentation is confirmed as a relevant variable for scrutinising patients with idiopathic infertility, beyond the evidently insufficient WHO semen analyses. Since both techniques yielded similar results, the reduced necessity of complex equipment when running SCD ought to be considered for a clinical setting.

Evaluation of risk factors' importance on adverse pregnancy and neonatal outcomes in women aged 40 years or older.

BACKGROUND: Women of advanced age (40 years or older) are generally, at risk for pregnancy and delivery related problems. In addition, there is limited knowledge on being of advanced age and having been given Assisted Reproductive Treatment (ART) and its association with negative obstetric outcomes. Therefore, data from the Swedish Medical Birth Register was used to investigate pregnancy and neonatal outcomes for women aged 40 or more who had given birth. The secondary aim was to compare the obstetric outcomes of women who had used ART and women who had not undergone ART while adjusting for marital status across the age groups. METHOD: Women of advanced age who had given birth in Sweden during 2007-2012 formed the index group, n = 37,558; a reference group of women comprised 71,472 women under the age of 40. An additional subgroup of women aged 45 or older when giving birth was also formed, n = 2229. The obstetric and neonatal data for all the women was derived from national register data. RESULTS: Women of advanced age were more often single, had undergone ART, and more often experienced adverse obstetric outcomes than did younger women. The neonate's health was also more often adversely affected expressed as being born with low birth weight and Small for Gestational Age (SGA), having lower Apgar scores, and having more health problems during the first week compared to the reference group. CONCLUSIONS: Women who are approaching the upper limit of fecundity are at greater risk for having children who are preterm and SGA. The adverse effects of being preterm and SGA may have negative long-term effects, not only on the children but also on the mothers. This needs to be addressed more frequently in a clinical setting when advising women of all ages on pregnancy and ART treatment.

The prevalence of primary ovarian insufficiency in Sweden; a national register study.

BACKGROUND: The current estimates of the prevalence of primary ovarian insufficiency (POI) are very variable, but are in most studies believed to be around 1%. It is also very likely tat the prevalence of POI differs between countries and over time. We therefore aimed to assess the prevalence of primary ovarian insufficiency in Sweden. METHODS: All 1,036,918 women born between 1973 and 1993 in Sweden were included. The prevalence of POI was based on data from the Swedish Patient Register through the diagnosis code or through the Prescribed Drug Register. The number of women below 40 years of age diagnosed with the ICD-10 diagnoses E28.3 or E89.4, and women who had been dispensed drugs for treatment of climacteric symptoms were included. RESULTS: Out of the 1,036,918 women, 19,253 (1.9%) had POI. The prevalence of spontaneous POI was 1.7% and the prevalence of iatrogenic POI was 0.2%. Most women (98.8%) with POI were identified from the Prescribed Drug Register; only 4.1% were found in the Patient Register, whereas 2.9% were identified in both registers. CONCLUSIONS: The total prevalence of POI was 1.9%, 95% CI: 1.7-2.1, indicating a higher prevalence than often previously reported.

Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study.

STUDY QUESTION: Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? SUMMARY ANSWER: A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. WHAT IS KNOWN ALREADY: Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. STUDY DESIGN, SIZE, DURATION: This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. MAIN RESULTS AND THE ROLE OF CHANCE: The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P = <0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = <0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i.e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. WIDER IMPLICATIONS OF THE FINDINGS: To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Not applicable.

Men becoming fathers by intracytoplasmic sperm injection were more often born small for gestational age.

Being born with nonoptimal birth characteristics decreases the chance of becoming a father. Urogenital malformations as well as metabolic syndrome are more common in men born small for gestational age (SGA) and could be contributing factors to the reduced fertility rate seen in these men. It could imply that men becoming fathers by assisted reproductive technology (ART) more often are born with low birth weight (LBW), preterm, and/or SGA than men conceiving without treatment and also that men where intracytoplasmic sperm injection (ICSI) had to be performed more often are born with nonoptimal birth characteristics than men where conventional in vitro fertilization (IVF) successfully could be used. In this retrospective, case-control study using Swedish national registers, we compared the birth characteristics of 1206 men who have become fathers by ART with a control group consisting of age-matched men who became fathers without treatment. The differences in birth characteristics between men becoming fathers by IVF and ICSI were also assessed. For men becoming fathers by ART, OR of being born with LBW was 1.66 (95% CI = 1.17-2.36) compared with fathers who conceived without treatment. OR of being born prematurely was 1.32 (95% CI = 1.00-1.77). Men becoming fathers via ICSI had a doubled increased likelihood of being born SGA compared with men who became fathers via IVF (OR = 2.12; 95% CI = 1.17-3.83). In conclusion, we have found that men becoming fathers by ICSI treatments had more often been born SGA than men becoming fathers by conventional IVF.

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

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

Internet-delivered applied relaxation for vasomotor symptoms in postmenopausal women: lessons from a failed trial.

Internet-delivered therapies have a short history and promising results have been shown for several health problems, particularly for psychiatric conditions. This study was a first attempt to evaluate whether Internet-delivered applied relaxation for hot flushes in postmenopausal women may be useful. Due to a high drop-out rate the study was prematurely terminated after inclusion of approximately two thirds of calculated women. The Internet-delivered applied relaxation must probably be modified for such populations and settings before it can be used further. This article will discuss the benefits and pitfalls to learn in order to meet the challenges of future studies. Clinical trial registration number: NCT01245907.

Effects of applied relaxation on vasomotor symptoms in postmenopausal women: a randomized controlled trial.

OBJECTIVE: This work aimed to study the efficacy of group therapy with applied relaxation on vasomotor symptoms and health-related quality of life in postmenopausal women. METHODS: In this open, randomized controlled trial, 60 healthy postmenopausal women with at least seven moderate to severe hot flashes per 24 hours were randomized to either group therapy with applied relaxation (n = 33) or untreated control group (n = 27) for 12 weeks. A follow-up visit was scheduled 3 months after the end of therapy or participation in the control group. Salivary cortisol was measured three times during a 6-month period. Hot flashes were recorded in self-registered diaries, and health-related quality of life was assessed with the Women's Health Questionnaire. RESULTS: The number of hot flashes decreased by 5.0 per 24 hours in the applied relaxation group compared with 1.9 in the control group on the 12th week (P < 0.001) and still remained at the same level at the 3-month follow-up (P < 0.001). Health-related quality of life for vasomotor symptoms, sleep, and memory improved significantly on the 12th week measurement in the applied relaxation group compared with the control group. Salivary cortisol concentration was lowered markedly in the applied relaxation group on a single measurement but was otherwise mainly stable in both groups. CONCLUSIONS: Applied relaxation can be used to treat vasomotor symptoms in healthy postmenopausal women.

Psychological well-being improves in women with breast cancer after treatment with applied relaxation or electro-acupuncture for vasomotor symptom.

The aim of this study was to evaluate the effect of applied relaxation and electro-acupuncture (EA) on psychological well-being in breast cancer-treated women with vasomotor symptoms. Thirty-eight breast cancer-treated postmenopausal women with vasomotor symptoms were included in the study. They were randomized to either treatment with electro-acupuncture (EA) (n = 19, three of them with tamoxifen) or applied relaxation (AR) (n = 19, five of them with tamoxifen) over a 12-week study period with six months follow-up. Vasomotor symptoms were registered daily. A visual analog scale was used to assess climacteric symptom, estimation of general well-being was made using the Symptom Checklist, and mood using the Mood Scale. These were applied during treatment and at follow-up. In total 31 women completed 12 weeks of treatment and six months of follow-up. Hot flushes were reduced by more than 50%. Climacteric symptoms significantly decreased during treatment and remained so six months after treatment in both groups. Psychological well-being significantly improved during therapy and at follow-up visits in both groups. Mood improved significantly in the electro-acupuncture treated group. In conclusion psychological well-being improved in women with breast cancer randomized to treatment with either AR or EA for vasomotor symptoms and we therefore suggest that further studies should be performed in order to evaluate and develop these alternative therapies.

Applied relaxation and oral estradiol treatment of vasomotor symptoms in postmenopausal women.

OBJECTIVE: The aim was to evaluate and compare the effects of applied relaxation and oral estradiol treatment on hot flushes, mood and psychological wellbeing in postmenopausal women. PATIENTS AND METHODS: In a prospective study, 30 postmenopausal women with vasomotor symptoms were randomized to applied relaxation or oral estradiol treatment during 12 weeks with 6 months follow-up. Number and severity of flushes were registered daily and Kupperman's Index and a general estimate of climacteric symptoms, Mood Scale and Symptom Check List were completed at baseline, 4, 8 and 12 weeks of treatment, and 3 and 6 months after therapy. RESULTS: After 12 weeks of treatment, the number of flushes/24 h decreased significantly over time in both treatment groups. In the group receiving applied relaxation, the mean number of flushes/24 h decreased from 6.0 (95% CI 4.5-7.6) to 3.0 (95% CI 2.1-3.9) after 12 weeks of treatment. The mean number of flushes/24 h was 1.7 (95% CI 0.7-2.5) at 6 months follow-up; i.e. a 72% decrease. In the estrogen group, the mean number of flushes/24h decreased from 8.4 to 0.8; i.e a 90% decrease in the number of flushes after 12 weeks of treatment. The significant change in flushes reached after 12 weeks of treatment and remained to 6 months after end of treatment in both groups. Estrogen therapy reduced flushes significantly faster than applied relaxation. General climacteric symptoms according to the Visual Analogue Scale and the Kupperman's Index decreased significantly over time in both groups. General mood (Mood Scale) increased significantly in the estrogen group, but not in the group receiving applied relaxation. Psychological wellbeing according to Symptom Checklist, increased significantly from baseline to 12 weeks in both groups. CONCLUSIONS: We suggest that applied relaxation may be used as an alternative treatment of vasomotor symptoms for postmenopausal women but should be further evaluated.