A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer.

STUDY QUESTION: Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone? SUMMARY ANSWER: The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone. WHAT IS KNOWN ALREADY: Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection. STUDY DESIGN, SIZE, DURATION: A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed. MAIN RESULTS AND THE ROLE OF CHANCE: In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics. LIMITATIONS, REASONS FOR CAUTION: During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks. WIDER IMPLICATIONS OF THE FINDINGS: The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone. STUDY FUNDING/COMPETING INTEREST(S): The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registration number NCT03445923. TRIAL REGISTRATION DATE: 26 February 2018. DATE OF FIRST PATIENT'S ENROLMENT: 11 June 2018.

The Association Between High Birth Weight and Long-Term Outcomes-Implications for Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis.

Background: Studies have shown that the prevalence of children born with high birth weight or large for gestational age (LGA) is increasing. This is true for spontaneous pregnancies; however, children born after frozen embryo transfer (FET) as part of assisted reproductive technology (ART) also have an elevated risk. In recent years, the practice of FET has increased rapidly and while the perinatal and obstetric risks are well-studied, less is known about the long-term health consequences. Objective: The aim of this systematic review was to describe the association between high birth weight and LGA on long-term child outcomes. Data Sources: PubMed, Scopus, and Web of Science were searched up to January 2021. Exposure included high birth weight and LGA. Long-term outcome variables included malignancies, psychiatric disorders, cardiovascular disease, and diabetes. Study Selection: Original studies published in English or Scandinavian languages were included. Studies with a control group were included while studies published as abstracts and case reports were excluded. Data Extraction: The methodological quality, in terms of risk of bias, was assessed by pairs of reviewers. Robins-I (www.methods.cochrane.org) was used for risk of bias assessment in original articles. For systematic reviews, AMSTAR (www.amstar.ca) was used. For certainty of evidence, we used the GRADE system. The systematic review followed PRISMA guidelines. When possible, meta-analyses were performed. Results: The search included 11,767 articles out of which 173 met the inclusion criteria and were included in the qualitative analysis, while 63 were included in quantitative synthesis (meta-analyses). High birth weight and/or LGA was associated with low to moderately elevated risks for certain malignancies in childhood, breast cancer, several psychiatric disorders, hypertension in childhood, and type 1 and 2 diabetes. Conclusions: Although the increased risks for adverse outcome in offspring associated with high birth weight and LGA represent serious health effects in childhood and in adulthood, the size of these effects seems moderate. The identified risk association should, however, be taken into account in decisions concerning fresh and frozen ART cycles and is of general importance in view of the increasing prevalence in high birthweight babies.

A systematic review and meta-analysis on the association between ICSI and chromosome abnormalities.

BACKGROUND: In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural abnormalities, as well as inherited abnormalities was described in children conceived by ICSI compared to both naturally conceived (NC) children and children conceived by standard IVF. The explanation for the observed increase in prevalence is not clear and has been suggested to reflect parental factors (e.g. age or sperm quality) or to be a result of the ICSI procedure itself. Over the years, the procedure, as well as the patient group, and indications for ICSI treatment have changed. OBJECTIVE AND RATIONALE: The objective of this systematic review and meta-analysis was to assess the prevalence of chromosome abnormalities in ICSI pregnancies and children and to examine any potentially increased risk compared to standard IVF and NC. SEARCH METHODS: Pubmed, Embase, Cochrane Libraries and Web of Science up to October 2020 were searched. Primary outcome measures were overall chromosome abnormalities and de novo abnormalities (including sex chromosome abnormalities and autosomal abnormalities). The secondary outcome was inherited abnormalities. We followed the PRISMA guidelines and relevant meta-analyses were performed. OUTCOMES: The search included 4648 articles, out of which 27 met the inclusion criteria, and 19 were included in quantitative synthesis (meta-analyses). The prevalence of chromosome abnormalities varied considerably between studies, possibly explained by large differences in sample size and patient demographics. Only five studies were eligible for pooled analyses on adjusted data. All studies had a critical risk of bias. Results from pooled adjusted data showed no evidence of an increased risk of overall chromosome abnormalities when comparing ICSI to either standard IVF (aOR 0.75 (95% CI 0.41-1.38)) or NC (aOR 1.29 (95% CI 0.69-2.43)). In contrast, meta-analyses on unadjusted data showed an increased risk of overall chromosome abnormalities in ICSI compared to both standard IVF (OR 1.42 (95% CI 1.09-1.85)) and NC (OR 2.46 (95% CI 1.52-3.99)) and an increased risk of de novo abnormalities in ICSI compared to NC (OR 2.62 (95% CI 2.07-3.31)). Yet, based on a very low certainty of evidence, the conclusion remains, that no indication of an increased risk of chromosome abnormalities in ICSI offspring could be found. If an increased risk of chromosome abnormalities in selected ICSI offspring should exist, the absolute risk continues to be small. WIDER IMPLICATIONS: This review provides an extensive overview of the existing evidence on the relationship between ICSI and chromosome abnormalities in the offspring. We highlight the need for well-designed large, prospective, controlled studies with systematic cytogenetic testing. Existing data are limited and, in many cases, marred by critical levels of bias.

The health of children conceived by ART: 'the chicken or the egg?'

Worldwide, more than 7 million children have now been born after ART: these delivery rates are steadily rising and now comprise 2-6% of births in the European countries. To achieve higher pregnancy rates, the transfer of two or more embryos was previously the gold standard in ART. However, recently the practise has moved towards a single embryo transfer policy to avoid multiple births. The positive consequences of the declining multiple birth rates after ART are decreasing perinatal risks and overall improved health for the ART progeny. In this review we summarize the risks for short- and long-term health in ART singletons and discuss if the increased health risks are associated with intrinsic maternal or paternal factors related to subfertility or to the ART treatments per se. Although the risks are modest, singletons born after ART are more likely to have adverse perinatal outcomes compared to spontaneously conceived (SC) singletons dependent on the ART method. Fresh embryo transfer is associated with a higher risk of small for gestational age babies (SGA), low birthweight and preterm birth (PTB), while frozen embryo transfer is associated with large-for-gestational age babies and pre-eclampsia. ICSI may be associated with a higher risk of birth defects and transferral of the poor semen quality to male progeny, while oocyte donation is associated with increased risk of SGA and pre-eclampsia. Concerning long-term health risks, the current evidence is limited but suggests an increased risk of altered blood pressure and cardiovascular function in ART children. The data that are available for malignancies seem reassuring, while results on neurodevelopmental health are more equivocal with a possible association between ART and cerebral palsy. The laboratory techniques used in ART may also play a role, as different embryo culture media give rise to different birthweights and growth patterns in children, while culture to blastocyst stage is associated with PTB. In addition, children born after ART have altered epigenetic profiles, and these alterations may be one of the key areas to explore to improve our understanding of adverse child outcomes after ART. A major challenge for research into adverse perinatal outcomes is the difficulty in separating the contribution of infertility per se from the ART treatment (i.e. 'the chicken or the egg'?). Choosing and having access to the appropriate control groups for the ART children in order to eliminate the influence of subfertility per se (thereby exploring the pure association between ART and child outcomes) is in itself challenging. However, studies including children of subfertile couples or of couples treated with milder fertility treatments, such as IUI, as controls show that perinatal risks in these cohorts are lower than for ART children but still higher than for SC indicating that both subfertility and ART influence the future outcome. Sibling studies, where a mother gave birth to both an ART and a SC child, support this theory as ART singletons had slightly poorer outcomes. The conclusion we can reach from the well designed studies aimed at disentangling the influence on child health of parental and ART factors is that both the chicken and the egg matter.

Fertility after cryopreservation of ovarian tissue due to cancer treatment. / Fertilitet etter kryopreservering av ovarialvev ved kreftbehandling.

BAKGRUNN: Kryopreservering av ovarialvev som fertilitetsbevarende metode tilbys prepubertale jenter og kvinner i reproduktiv alder med høy risiko for å utvikle prematur ovarialsvikt i forbindelse med medisinsk eller kirurgisk behandling. I denne studien ønsket vi å kartlegge fertilitet og prematur ovarialsvikt hos kvinner som har fått gjort kryopreservering av ovarialvev i forbindelse med kreftbehandling. MATERIALE OG METODE: Et spørreskjema ble i 2014 sendt til 94 kvinner over 18 år som i perioden 2004-12 hadde fått kryopreservert ovarialvev i forbindelse med behandling for en malign tilstand. Skjemaet inneholdt spørsmål om menstruasjonsfrekvens, prevensjonsbruk, fertilitet, fremtidig barneønske og sannsynlighet for at de ville benytte ovarialvevet senere. Av de 77 kvinnene som returnerte spørreskjemaet, ble 74 kvinner inkludert i studien. RESULTATER: Totalt 20 av 74 kvinner (27 %) hadde prematur ovarialsvikt definert som opphør av ovarialfunksjonen før 40 års alder. Risikoen var lavest hos kvinner behandlet for brystkreft (5 %) og høyest hos kvinner behandlet for leukemi (75 %). Størst risiko for prematur ovarialsvikt fant man i pasientgruppene som hadde gjennomgått stamcelletransplantasjon, strålebehandling mot helkropp og/eller abdomen og bekken. Til sammen hadde 22 kvinner født 31 barn etter kreftbehandlingen, hvorav to etter reimplantasjon av ovarialvev. FORTOLKNING: Risikoen for å utvikle prematur ovarialsvikt er avhengig av pasientens kreftdiagnose. Hvilke fertilitetsbevarende tiltak som anbefales, bør differensieres avhengig av pasienten kreftdiagnose og planlagt behandling.

The effect of paternal factors on perinatal and paediatric outcomes: a systematic review and meta-analysis.

BACKGROUND: Maternal factors, including increasing childbearing age and various life-style factors, are associated with poorer short- and long-term outcomes for children, whereas knowledge of paternal parameters is limited. Recently, increasing paternal age has been associated with adverse obstetric outcomes, birth defects, autism spectrum disorders and schizophrenia in children. OBJECTIVE AND RATIONALE: The aim of this systematic review is to describe the influence of paternal factors on adverse short- and long-term child outcomes. SEARCH METHODS: PubMed, Embase and Cochrane databases up to January 2017 were searched. Paternal factors examined included paternal age and life-style factors such as body mass index (BMI), adiposity and cigarette smoking. The outcome variables assessed were short-term outcomes such as preterm birth, low birth weight, small for gestational age (SGA), stillbirth, birth defects and chromosomal anomalies. Long-term outcome variables included mortality, cancers, psychiatric diseases/disorders and metabolic diseases. The systematic review follows PRISMA guidelines. Relevant meta-analyses were performed. OUTCOMES: The search included 14 371 articles out of which 238 met the inclusion criteria, and 81 were included in quantitative synthesis (meta-analyses). Paternal age and paternal life-style factors have an association with adverse outcome in offspring. This is particularly evident for psychiatric disorders such as autism, autism spectrum disorders and schizophrenia, but an association is also found with stillbirth, any birth defects, orofacial clefts and trisomy 21. Paternal height, but not BMI, is associated with birth weight in offspring while paternal BMI is associated with BMI, weight and/or body fat in childhood. Paternal smoking is found to be associated with an increase in SGA, birth defects such as congenital heart defects, and orofacial clefts, cancers, brain tumours and acute lymphoblastic leukaemia. These associations are significant although moderate in size, with most pooled estimates between 1.05 and 1.5, and none exceeding 2.0. WIDER IMPLICATIONS: Although the increased risks of adverse outcome in offspring associated with paternal factors and identified in this report represent serious health effects, the magnitude of these effects seems modest.

Cancer Risk in Women Treated with Fertility Drugs According to Parity Status-A Registry-based Cohort Study.

Background: Long-term safety of assisted reproductive techniques (ART) is of interest as their use is increasing. Cancer risk is known to be affected by parity. This study examined the risk of cancer after fertility treatment, stratified by women's parity.Methods: Data were obtained from all women (n = 1,353,724) born in Norway between 1960 and 1996. Drug exposure data (2004-2014) were obtained from the Norwegian Prescription Database (drugs used in ART and clomiphene citrate). The Medical Birth Registry of Norway provided parity status. HRs were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer, and malignant melanoma.Results: In 12,354,392 person-years of follow-up, 20,128 women were diagnosed with cancer. All-site cancer risk was 1.14 [95% confidence interval (95% CI), 1.03-1.26] and 1.10 (95% CI, 0.98-1.23) after clomiphene citrate and ART exposure, respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR, 2.49; 95% CI, 1.30-4.78; and HR, 1.62; 95% CI, 0.78-3.35) versus parous women (HR, 1.37; 95% CI, 0.64-2.96; and HR, 0.87; 95% CI, 0.33-2.27). Elevated risk of endometrial cancers was observed for clomiphene citrate exposure in nulliparous women (HR, 4.49; 95% CI, 2.66-7.60 vs. HR, 1.52; 95% CI, 0.67-3.42). Risk was elevated for breast cancer in parous women exposed to clomiphene citrate (HR, 1.26; 95% CI, 1.03-1.54) for thyroid cancer and among nulliparous women after ART treatment (HR, 2.19; 95% CI, 1.08-4.44).Conclusions: Clomiphene citrate appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity.Impact: Continued monitoring of fertility treatments is warranted. Cancer Epidemiol Biomarkers Prev; 26(6); 953-62. ©2017 AACR.

Literature review on cancer risk in children born after fertility treatment suggests increased risk of haematological cancers.

Medically assisted fertility treatment, including assisted reproductive technology (ART), is increasingly being used and the subsequent child health outcomes are of interest. Some studies have suggested an elevated risk of somatic morbidity, while others have reported an elevated cancer risk. This review summarises the literature on fertility treatments and childhood cancer, based on 23 cohort and case-control studies. CONCLUSION: The findings varied, but reassuring results on overall childhood cancer and fertility treatment were observed. However, some studies suggested an elevated risk of haematological cancers. More large population-based studies are needed, and the growing population of ART children should be monitored.

Risk of Cancer in Children Conceived by Assisted Reproductive Technology.

BACKGROUND AND OBJECTIVE: An increasing number of children are born after assisted reproductive technology (ART), and monitoring their long-term health effects is of interest. This study compares cancer risk in children conceived by ART to that in children conceived without. METHODS: The Medical Birth Registry of Norway contains individual information on all children born in Norway (including information of ART conceptions). All children born between 1984 and 2011 constituted the study cohort, and cancer data were obtained from the Cancer Registry of Norway. Follow-up started at date of birth and ended on the date of the first cancer diagnosis, death, emigration, or December 31, 2011. A Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer risk between children conceived by ART and those not. Cancer risk was also assessed separately for all childhood cancer types. RESULTS: The study cohort comprised 1 628 658 children, of which 25 782 were conceived by ART. Of the total 4554 cancers, 51 occurred in ART-conceived children. Risk of overall cancer was not significantly elevated (HR 1.21; 95% CI 0.90-1.63). However, increased risk of leukemia was observed for children conceived by ART compared with those who were not (HR 1.67; 95% CI 1.02-2.73). Elevated risk of Hodgkin's lymphoma was also found for ART-conceived children (HR 3.63; 95% CI 1.12-11.72), although this was based on small numbers. CONCLUSIONS: This population-based cohort study found elevated risks of leukemia and Hodgkin's lymphoma in children conceived by ART.

Risk of breast cancer following fertility treatment--a registry based cohort study of parous women in Norway.

Despite increasing numbers of women availing themselves of assisted reproductive technology (ART), effects on cancer risk remain unresolved. Given hormonal exposures, breast cancer risk is of particular concern. The aim of this study is to investigate breast cancer risk amongst women giving birth following ART as compared to that amongst women who gave birth without ART. Data on all women who gave birth in Norway with or without ART, between 1984 and 2010 were obtained from the Medical Birth Registry of Norway (MBRN). 808,834 women eligible for study were linked to the Cancer Registry of Norway. Cox proportional models computed hazard ratios (HR) and 95% confidence intervals (CI) of breast cancer between the two groups, adjusting for age, parity, age at first birth, calendar period and region of residence. In total, 8,037 women were diagnosed with breast cancer during the study period, 138 ART women and 7,899 unexposed. Total follow-up time was 12,401,121 person-years (median 16.0); median age at entry was 32.5 years (range 18.6-49.9) for ART women and 26.3 (range 10.5-54.6) for unexposed. Women exposed to ART had an elevated risk of breast cancer (adjusted HR 1.20, 95% CI 1.01-1.42). Subgroup analyses gave an HR of 1.30 (95% CI 1.07-1.57) for women treated with IVF and 1.35 (95 % CI 1.07-1.71) for women with follow-up >10 years, compared with controls. Our findings of increased risk in the study population warrant continued monitoring of women treated with ART as this population advances into more typical cancer age ranges.

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

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

In vitro fertilization is a successful treatment in endometriosis-associated infertility.

OBJECTIVE: To assess success rates of IVF and intracytoplasmic sperm injection in women with various stages of endometriosis. DESIGN: Retrospective cohort study. SETTING: Reproductive medicine unit in a university hospital. PATIENT(S): Infertile women (n = 2,245) with various stages of endometriosis or tubal factor infertility. INTERVENTION(S): IVF or intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Dose of FSH, number of oocytes retrieved, fertilization rate, implantation rate, pregnancy rate (PR), live birth/ongoing PR. RESULT(S): Women with endometriosis had similar pregnancy and live birth/ongoing PR as did women with tubal factor infertility, but the American Society for Reproductive Medicine (ASRM) stage I and II endometriosis patients had a lower fertilization rate, and stage III and IV patients required more FSH and had fewer oocytes retrieved. Splitting the stage III and IV groups into patients with and without endometriomas showed that the endometrioma group required more FSH and had a significantly lower pregnancy and live birth/ongoing PR. CONCLUSION(S): With the exception of patients with endometrioma, infertile women with various stages of endometriosis have the same success rates with IVF and intracytoplasmic sperm injection as patients with tubal factor. This contrasts with the systematic review on which the European Society of Human Reproduction and Embryology bases its recommendations.

Infertility treatment and the risk of cancer.

BACKGROUND: A possible correlation between hormonal stimulation during treatment of infertility and the risk of cancer of the breast, the ovaries, the cervix or the uterus has been investigated in a number of epidemiological studies. The purpose of this article is to review the relevant literature and summarise the findings. KNOWLEDGE BASE: This review article is based on literature searches in the databases MEDLINE, Cochrane and EMBASE. RESULTS: No studies showed a specific general correlation between hormonal ovulatory stimulation used as pre-treatment to assisted fertilisation and an increased risk of cancer of the breast, the ovaries, the cervix or the uterus. Most studies detected no increased risk. Some studies, however, showed an increased risk of cancer among certain sub-groups, such as women who have received repeated treatment with clomiphene citrate. INTERPRETATION: On the basis of the studies reviewed, the conclusions are ambiguous. It is therefore necessary to monitor the long-term effects of infertility treatment on women's health. Further good-quality large-scale population studies are necessary, with longer follow-up periods and better adjustment for confounding factors.

Spermatogenesis and fertility outcome in male hypogonadotrophic hypogonadism.

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

[Induction of spermatogenesis in hypogonadotrophic hypogonadism]. / Induksjon av spermatogenese ved hypogonadotrop hypogonadisme.

BACKGROUND: Reduced or missing sperm production is the main reason for infertility in a third of the couples who seek treatment. An uncommon cause of testicular failure is hypogonadotrophic hypogonadism. This review article discusses causes of this condition in men, medical treatment and prognosis with regard to fertility. MATERIAL AND METHODS: The review is based on a recent literature survey and many years of clinical experience with infertile patients. RESULTS AND INTERPRETATION: Hormonal regulation of the spermatogenesis involves complex interaction between structural elements (paracrine and endocrine) in the testicle and the endocrine system. Hormonal treatment of men with hypogonadotrophic hypogonadism comprises injections of gonadotrophins, administered by the patient in close cooperation with a specialist. It may be necessary to maintain this treatment for up to two years, but it is usually effective in initiating or restoring of spermatogenesis.

Intracytoplasmic sperm injection (ICSI) in unexplained and stage I endometriosis-associated infertility after fertilization failure with in vitro fertilization (IVF).

PURPOSE: To investigate possible differences between unexplained and stage I endometriosis-associated infertility in ICSI cycles conducted after low fertilization (<20%) in preceding IVF cycles with normal semen parameters. METHODS: Retrospective cohort study consisting of patients with unexplained (n=48) and stage I endometriosis-associated infertility (n=43) with a minimum of one IVF cycle with <20% fertilized oocytes and normal semen quality, treated with ICSI from January 1997 to January 2006. Age matched male factor infertility patients (n=91) were used as controls. RESULTS: Diploid fertilization rate was significantly lower in the stage I endometriosis-associated infertility group compared to the unexplained infertility group. Score of the transferred embryos, implantation rate, pregnancy rate and outcome were similar in the two groups. CONCLUSIONS: ICSI appears to be an efficient treatment option after fertilization failure with IVF in unexplained and stage I endometriosis-associated infertility.

Pregnancy outcome after IVF and ICSI in unexplained, endometriosis-associated and tubal factor infertility.

BACKGROUND: This study was undertaken in order to compare pregnancy outcome after IVF and ICSI in unexplained and endometriosis-associated infertility using tubal factor infertility as controls. METHODS: This was a retrospective cohort study of early IVF/ICSI pregnancies verified by serum hCG measurement, comparing the subsequent outcome in unexplained (n = 274) and minimal endometriosis-associated (n = 212) with tubal factor (n = 540) infertility as controls. From January 1990 to December 2002, 1026 conception cycles after treatment with IVF or ICSI complied with the inclusion criteria. RESULTS: Live birth rate, twin birth rate after transfer of two embryos and abortion rate prior to 6 weeks of gestation were superior for the unexplained (78.8, 23.5 and 11.7%) compared to endometriosis-associated (66.0, 15.0 and 19.3%) and tubal factor (66.7, 18.1 and 18.0%) infertility groups (P < 0.05). Compared to the endometriosis-associated, the unexplained infertility group attained a higher pregnancy rate after the first treatment cycle (P < 0.05). CONCLUSIONS: The overall better outcome for the unexplained infertility group with respect to live birth rate, twin birth rate and early abortion rate compared to the minimal peritoneal endometriosis-associated and tubal factor infertility groups might be a guide to select diagnostic groups for single embryo transfer and be useful in patient counselling.

Impact of overweight and underweight on assisted reproduction treatment.

BACKGROUND: Underweight and overweight may affect reproduction and interfere with treatment of infertility. The purpose of this report is to describe the independent effect of body weight on treatment with IVF and ICSI. METHODS: Records of 5019 IVF or ICSI treatments in 2660 couples were reviewed. The influence of body mass index (BMI) on treatment outcome was examined, after accounting for differences in age and infertility diagnosis. RESULTS: The cumulative live birth rate within three treatment cycles was 41.4% [95% confidence interval (CI) 32.1-50.7] in obese women with BMI > or =30 kg/m2 and 50.3 (95% CI 47.0-53.7) in normal weight women with BMI 18.5-24.9 kg/m2. Obesity was associated with an increased risk of early pregnancy loss occurring before 6 weeks gestation. Positive correlation between BMI and gonadotrophin requirement during stimulation and negative correlation between BMI and number of collected oocytes were observed. Underweight (BMI <18.5 kg/m2) was not related to an impaired outcome of IVF or ICSI. CONCLUSIONS: Obesity is associated with lower chances for live birth after IVF and ICSI and with an impaired response to ovarian stimulation.

[Congenital malformations in children born after assisted fertilization in Norway]. / Medfødte misdannelser hos barn født etter assistert befruktning i Norge.

The aim of this study was to compare the prevalence at birth of birth defects in children born after intracytoplasmatic sperm injection (ICSI) and children born after traditional in vitro fertilisation (IVF). Altogether 553 children were born after ICSI treatment in Norway during the period 1996-1998 (351 singletons, 95 twins-pairs and 4 triplets) while 1731 were born after IVF treatment (1004 singletons, 344 sets of twins and 13 triplets). Birth defects were registered in 5.42% of children born after ICSI and in 5.14% of children born after IVF; 3,07% and 3.00% respectively were major birth defects. We conclude that intracytoplasmic sperm injection does not imply a significant increase in the prevalence at birth of birth defects compared to children conceived by traditional IVF.