Assisted reproductive technology and severe postpartum haemorrhage: a case-control study.

OBJECTIVE: To investigate the association between assisted reproductive technology and severe postpartum haemorrhage. DESIGN: Case-control study. SETTING: The study was conducted in Norway; Division of Gynaecology and Obstetrics at Oslo University Hospital and Department of Obstetrics and Gynaecology at Drammen Hospital. POPULATION: A source population including all women admitted for delivery at Oslo University Hospital and Drammen Hospital during the time period 1 January 2008 to 31 December 2011. The study population consisted of all cases of severe postpartum haemorrhage (n = 1064) and a random sample of controls (n = 2059). METHODS: We used an explanatory strategy in the analysis, with multivariable logistic regression. MAIN OUTCOME MEASURES: Severe postpartum haemorrhage; defined as blood loss ≥1500 ml or need for blood transfusion. RESULTS: Assisted reproductive technology was associated with an increased risk of severe postpartum haemorrhage (crude OR = 2.92; 95% CI 2.18-3.92, P < 0.001). Mode of delivery and anticoagulant medication had significant confounding effects. Strong interaction was found for multiple pregnancies. After adjusting for confounding and interaction, an increased risk was observed both in the strata of multiple pregnancies (adjusted OR = 7.00, 95% CI 2.70-18.12, P < 0.001), and in the strata of single gestation (adjusted OR = 1.58, 95% CI 1.12-2.24, P = 0.010). CONCLUSIONS: Our findings warrant an increased awareness of the risk of severe postpartum haemorrhage in women conceiving with assisted reproductive technology. Furthermore, the high risk of severe postpartum haemorrhage in the presence of a twin or triplet pregnancy is an additional argument for single embryo transfer. TWEETABLE ABSTRACT: Assisted reproductive technology is associated with an increased risk of severe postpartum haemorrhage.

Cancer risk among parous women following assisted reproductive technology.

STUDY QUESTION: Do women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women who give birth without ART? SUMMARY ANSWER: Without correction, the results indicate an increase in overall cancer risk, as well as a 50% increase in risk of CNS cancer for women giving birth after ART, however the results were not significant after correcting for multiple analyses. WHAT IS KNOWN ALREADY: Studies regarding the effects of hormonal treatments involved with ART on subsequent cancer risk have provided inconsistent results, and it has also been suggested that infertility itself could be a contributory factor. STUDY DESIGN, SIZE, DURATION: A population-based cohort consisting of all women registered in the Medical Birth Registry of Norway as having given birth between 1 January 1984 and 31 December 2010 was assembled (n = 812 986). Cancers were identified by linkage to the Cancer Registry of Norway. Study subjects were followed from start of first pregnancy during the observational period until the first cancer, death, emigration, or 31 December 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the total study population (n = 806 248), 16 525 gave birth to a child following ART. Cox regression analysis computed hazard ratios (HR) and 95% confidence intervals (CI) comparing cancer risk between ART women and non-ART women; for overall cancer, and for cervical, ovarian, uterine, central nervous system (CNS), colorectal and thyroid cancers, and for malignant melanoma. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 22 282 cohort members were diagnosed with cancer, of which 338 were ART women and 21 944 non-ART women. The results showed an elevated risk in one out of seven sites for ART women. The HR for cancer of the CNS was 1.50 (95% CI 1.03- 2.18), and among those specifically subjected to IVF (without ICSI) the HR was 1.83 (95% CI 1.22-2.73). Analysis of risk of overall cancer gave an HR of 1.16 (95% CI 1.04-1.29). Among those who had delivered only one child by the end of follow-up, the HR for ovarian cancer was 2.00 (95% CI 1.08-3.65), and for those nulliparous at entry the HR was 1.80 (95% CI 1.04-3.11). However, all findings became non-significant after correcting for multiple analyses. LIMITATIONS, REASONS FOR CAUTION: The results of elevated risk of overall cancer and CNS cancer lost significance when adjusting for multiple analyses, implying an important limitation of the study. The follow-up time was relatively short, especially for ART women. In addition, as the cohort was relatively young, there were few incident cancers, especially for some rarer cancer forms, such as uterine cancer. Risk assessments according to different causes of infertility could not be done. WIDER IMPLICATIONS OF THE FINDINGS: In light of the findings in the present study, further studies should be made on risk of CNS and ovarian cancer, and continued monitoring of all those treated with ART is encouraged. Our findings may only be generalizable to women who give birth after ART, and the risk for women who remain nulliparous after ART remains to be assessed. STUDY FUNDING/COMPETING INTEREST: The study was funded by the Norwegian National Advisory Unit on Women's Health. All authors claim no competing interests.

Obstetric and perinatal risks after the use of donor sperm: A systematic review and meta-analysis.

Donor sperm is widely used in infertility treatments. The purpose of the study was to investigate, whether use of donor sperm in intrauterine insemination (IUI) or in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments affect maternal and perinatal risks compared with spontaneously conceived pregnancies or use of partner sperm in IUI, IVF or ICSI. We provide a systematic review and meta-analyses on the most clinically relevant obstetric and perinatal outcomes after use of donor sperm compared with partner sperm: hypertensive disorders of pregnancy, preeclampsia, low birth weight, and preterm birth. Our meta-analyses showed an increased risk for preeclampsia (pooled adjusted odds ratio (aOR) 1.77, 95% CI 1.26-2.48) and hypertensive disorders of pregnancy (pooled aOR 1.55, 95%, CI 1.20-2.00) in pregnancies resulting from IUI with donor sperm compared with IUI with partner sperm. No increased risk was seen for low birth weight or preterm birth after the use of donor sperm in IUI compared with the use of partner sperm in IUI. Subgroup analysis for singletons only did not change these results. The meta-analysis on low birth weight showed a lower risk after in IVF with donor sperm compared with IVF with partner sperm (pooled aOR 0.89, 95% CI 0.83-0.94). For hypertensive disorders of pregnancy, preeclampsia and preterm birth, no difference was found between IVF with donor sperm vs. partner sperm. Patients need to be informed about the moderately increased risk of hypertensive disorders of pregnancy and preeclampsia in pregnancies after IUI with donor sperm.

Contraceptive Choices and Counseling in Norwegian Female Renal Transplant Recipients.

BACKGROUND: There are major gaps in the understanding of sexual and reproductive health in female renal transplant recipients. METHODS: In this Norwegian multicenter retrospective observational study, 118 female renal transplant recipients aged 22 to 49 years responded to a questionnaire on fertility, contraceptive use, and pregnancy. RESULTS: More than one-third (37%) of patients reported that they did not receive advice on contraceptive methods from health care personnel in the early post-transplant phase. These women used effective contraceptive methods less often. Nearly half of the patients (45%) reported that they had not received any advice on timing of conception after transplant. From 95 pregnancies after renal transplant, 52 (55%) resulted in live births. CONCLUSION: Counseling on contraceptive methods should be part of standard care in conjunction with transplantation. More than one-third of young female renal transplant recipients of reproductive age could not recall having received advice from health care personnel about contraceptive use, and nearly half of the patients did not receive preconceptional advice after transplant. Although the current study does not discriminate between lack of advice and recall bias, the findings signal the need for improved counseling on female sexual and reproductive health after renal transplant.

Accessory sex gland function in normal young (20-25 years) and middle-aged (50-55 years) men.

A comparison of various parameters of prostatic and vesicular secretory function was made between the seminal plasma of young (20-25 years; n = 23) and middle-aged (50-55 years; n = 19) male volunteers. These parameters included prostatic acid phosphatase, zinc, citric acid, spermine, spermidine, putrescine (prostatic origin), fructose, and prostaglandin E (vesicular origin), in addition to protein and testosterone. Spermatozoa were counted and monitored for abnormalities. The concentration in the ejaculate of the majority of the parameters investigated did not change with age, although the total contribution to the ejaculate from the prostate and seminal vesicles was reduced significantly in the older men. The concentration of three constituents was significantly altered in the older age group: putrescine (P less than 0.001) and prostaglandin E (P less than 0.01) were reduced, while zinc levels were elevated (P less than 0.05). These changes are discussed in relation to possible disturbances of prostate function and pathology in the middle-aged man.

The value of anamnestic information regarding previous genital infection in male fertility investigation.

The study was designed to assess the value of information from male subjects under fertility investigation, regarding previous genital infection, in clarifying the causes of depressed sperm quality. Information was gathered using a questionnaire which was sent to 312 men who had previously attended our laboratory for semen analysis. A previous sexual transmitted disease (STD) in the male partner did not significantly influence the sperm quality or the pregnancy rate. However, a previous STD in the female was generally associated with a lower pregnancy rate. Previous episodes with urethral discharge, dysuria, pain with ejaculation or suprapubic discomfort had little relevance for the subsequent sperm quality. The results indicate that, in general, information provided by men under fertility investigation, regarding previous genital infections or symptoms, is only of limited value in elucidating the cause of impaired sperm quality.

Lifestyles of men in barren couples and their relationships to sperm quality.

This study is based on a questionnaire which focused on the possible association between lifestyle factors and male fertility in a group of 252 men attending our laboratory in connection with a fertility investigation. Their answers were correlated to sperm quality. No association could be documented between sperm quality and smoking habits, coffee drinking, a moderate alcohol intake, exposure to heat (sauna, hot baths, type of underwear, sedentary activities) or physical activities in their leisure time. In contrast, the reported average ejaculation frequency was significantly positively correlated to the motility of the sperm (% progressive) but inversely related to the proportion of sperm with abnormal morphology and semen volume. This indicates that the lifestyle of the subject has little, if any, impact on semen quality, at least within the limits recorded in the present study.

[Male infertility. Significance of life and occupation]. / Mannlig infertilitet. Betydning av livsstil og yrke.

A retrospective study was carried out which focused on the impact of lifestyle and exposure to different external factors on sperm quality. A questionnaire was sent to 312 men who had previously attended our laboratory for semen analysis. Their answers were correlated to sperm quality. Men exposed to a relatively high degree of X-rays were found to have significantly reduced sperm count. A previous symptomatic genital infection did not significantly influence the sperm quality, but an earlier sexually transmitted disease in the female partner was associated with a reduced rate of pregnancy. Frequency of ejaculation was significantly positively correlated to sperm motility and inversely related to both semen volume and proportion of sperm with abnormal morphology. Information on exposure to the remaining factors was not related to reduced sperm quality or fertility.

Seminal plasma lead, cadmium and zinc in relation to tobacco consumption.

The total quantity of zinc in the ejaculates of smokers was significantly lower than in non-smokers. This was not related to a significant increase in the quantities of seminal cadmium or lead, or to a decrease in sperm quality in the smoking group. It appears that tobacco consumption may have to exceed 20 cigarettes/day before a noticeable increase in seminal cadmium can be recorded. It is suggested that this reduction in zinc secretion may jeopardize the content of chromatin zinc, and thereby the stability of the sperm chromatin. This may then contribute to reproductive failure or have consequences for fetal development.

[Infertility studies in men]. / Menn under infertilitetsutredning.

This study summarizes the results of a questionnaire sent to 312 men involved in a fertility investigation. The answers illustrate the psychological problems linked to the infertile state, and indicate that men are generally well orientated about the extent of the problem. In the majority of cases, the infertile couples first contacted a gynecologist rather than a general practioner or other specialist. In over one third of the cases, this contact occurred within the first 12 months of attempting to achieve a pregnancy. The study implies an increasing negative attitude to donor insemination, and approximately one fifth of the men had at some time consulted fringe medicine.

Life styles of men in barren couples and their relationship to sperm quality.

This study is based on a questionnaire which focused on the possible association between life-style factors and male fertility in a group of 252 men attending our laboratory in connection with a fertility investigation. Their answers were correlated to sperm quality. No association could be documented between sperm quality and smoking habits, coffee drinking, a moderate alcohol intake, exposure to heat (sauna, hot baths, type of underwear, sedentary activities), or physical activities in their leisure time. In contrast, the reported average ejaculation frequency was significantly positively correlated to the motility of the sperm (% progressive), and inversely related to the proportion of sperm with abnormal morphology and semen volume. This indicates that the life style of the subject has little if any impact on semen quality, at least within the limits recorded in the present study.

Selenium in human male reproductive organs.

The objective of the study was to obtain information on the concentration and distribution of selenium throughout the human male reproductive tract. Material was removed at autopsy from 41 men who had died suddenly and unexpectedly. Semen samples were also provided from 184 men attending an andrology clinic for fertility investigation and from 32 healthy volunteers. Significant positive correlations in the selenium concentration were demonstrated between the different reproductive organs, the testis having the highest concentrations. No correlation was found between the concentration of selenium in the genital organs and liver, kidney or blood, suggesting that its uptake and/or biochemical activity in the reproductive organs may be controlled by similar mechanisms not shared by the other organs. No significant age-dependent changes could be detected in tissue selenium concentrations. In a group of men under fertility investigation, a significant positive correlation was obtained between seminal plasma concentrations of selenium and concentrations of spermatozoa in the same ejaculate. A significant positive correlation between concentrations of zinc and selenium in the same ejaculates indicated that selenium may arise largely from the prostate gland.

Male partners in infertile couples. Personal attitudes and contact with the Norwegian health service.

The present study summarizes the results of a questionnaire sent to 312 men involved in a fertility investigation. The answers illustrate the psychological problems linked to the infertile state, indicate that men are generally well orientated about the extent of the problem and imply an increasing negative attitude to donor insemination. In the majority of cases, the infertile couples first contacted a gynecologist rather than a general practitioner or other specialist. In over one third of the cases, this contact occurred within the first 12 months of attempting to procure a pregnancy. In most cases, the male partner was already involved in the fertility investigation at the start. Approximately one fifth had at some time consulted fringe medicine (e.g. homeopathy or acupuncture).

[Smoking and sperm quality in men undergoing fertility studies]. / Røyking og spermiekvalitet hos menn under fertilitetsutredning.

The sperm quality (sperm number, concentration, motility, morphology and vitality) of 350 men under fertility investigation were compared in relation to their smoking habits. No significant differences (Kruskal-Wallis test) in sperm quality could be demonstrated between non-smokers, moderate smokers (1-14 cigarettes/day) and heavy smokers (15-40 cigarettes/day). This was true when all the data were analyzed together and when analyzed separately for oligospermic/hypospermic men (1-39) or for men with reduced forward motility (less than 25% of sperm cells with progressive movement). The distribution of non-smokers, moderate and heavy smokers was the same in groups of men with normal sperm quality as in groups with reduced quality. The present study does not provide support for the contention that smoking has deleterious effects on sperm quality, at least when using conventional parameters.

Concentrations of lead, cadmium and zinc in the tissues of reproductive organs of men.

The concentrations of lead in blood and the concentrations of lead, cadmium and zinc in tissues were determined in various reproductive organs, liver and kidney removed at necropsy from 41 men who had died suddenly. None of the reproductive organs specifically accumulated lead and no significant correlation could be demonstrated between blood and organ concentrations or between concentrations and age, occupation or urban/rural background of the subject. Unlike lead, the tissue concentrations of cadmium increased with increasing age in all of the reproductive organs examined. Of these, the epididymides and seminal vesicles contained the highest concentrations. Whereas prostatic zinc also exhibited a significant age-dependent increase, the concentrations in the testes declined with age. The age-dependent increase in testicular cadmium did not become apparent until after the fourth decade, when any potentially deleterious impact on male fertility has less relevance. It is concluded that measurable amounts of lead and cadmium are present in all of the human reproductive organs but their organ and age distribution do not offer strong support for their involvement in the aetiology of male infertility or in the genesis of glandular neoplasms.

Effects of oestrogen-induced hyperprolactinemia on the rat prostate.

Exposure of intact rats to increasing doses of oestradiol-17 beta in the presence of a constant amount of exogenous androgen caused a dose-related increase in the concentration of zinc in the lateral lobes and a decrease in the levels of ventral lobe prolactin binding. These changes occurred concomitantly with a dose-dependent increase in plasma prolactin levels, and could not be obtained in hypophysectomized rats given the same steroid treatment. In the intact animals a dose-dependent decrease in the responsiveness of the prostaglandin E1-dependent adenylyl cyclase in the ventral lobe was observed, an effect which has earlier been shown to be prolactin mediated. The results indicate that oestrogen has indirect effects on specific parameters of prostate function by inducing a relative hyperprolactinemia. This model may be useful in studying effects of chronically and physiologically elevated levels of endogenous prolactin on the rat prostate.

Human sperm characteristics during frequent ejaculation.

Sperm concentration, morphology, DNA condensation and nuclear protein pattern as well as sperm adenylate cyclase were evaluated in semen samples provided by 7 volunteers every 8 h for 2 days. During the observation period, sperm concentration and total sperm number decreased but began to return towards normal after a 3-day abstinence period. No increase in the proportion of immature sperm cells was observed by light microscopy. Total adenylate cyclase (EC 4.6.1.1) increased significantly per cell, due to an increase in the soluble component while the particulate component remained relatively constant. Microflow fluorometry revealed no consistent alterations in the DNA or nuclear protein distribution. We conclude that although a high frequency of ejaculation does not disturb the conventional measures of sperm integrity, such as DNA condensation, there are major changes in at least one biochemical measurement, the activity of soluble adenylate cyclase.

Cigarette smoking and human sperm quality assessed by laser-Doppler spectroscopy and DNA flow cytometry.

The sperm qualities of 350 men under fertility investigation were compared in relation to their smoking habits. The sperm variables included number, motility, morphology and vitality. Sperm motility was assessed objectively by laser-Doppler spectroscopy. In a randomly selected group, sperm samples were subjected to flow cytometry to assess the levels of DNA condensation. No significant differences (Kruskal-Wallis' test) in any aspect of sperm quality including DNA distribution could be demonstrated between non-smokers, moderate smokers (1-14 cigarettes/day) and heavy smokers (15-40 cigarettes/day). This was true when the data were pooled and when oligozoospermic/hypozoospermic ejaculates (1-39 x 10(6)/ml) and asthenozoospermic ejaculates (less than 25% of sperm cells with progressive movement) were analysed separately. The distribution of non-smokers, moderate and heavy smokers was the same in groups of men with normal sperm quality as those with impaired quality. The present study does not provide support for the contention that smoking has deleterious effects on sperm quality, at least using conventional parameters.

Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis.

We investigated the frequency of spontaneous apoptosis and expression of the Bcl-2 family of proteins during normal spermatogenesis in man. Testicular tissue with both normal morphology and DNA content was obtained from necro-donors and fixed in Bouin's solution. A TdT-mediated dUTP end-labelling method (TUNEL) was used for the detection of apoptotic cells. Expression of apoptosis regulatory Bcl-2 family proteins and of p53 and p21(Waf1) was assessed by immunohistochemistry. Germ cell apoptosis was detected in all testes and was mainly seen in primary spermatocytes and spermatids and in a few spermatogonia. Bcl-2 and Bak were preferentially expressed in the compartments of spermatocytes and differentiating spermatids, while Bcl-x was preferentially expressed in spermatogonia. Bax showed a preferential expression in nuclei of round spermatids, whereas Bad was only seen in the acrosome region of various stages of spermatids. Mcl-1 staining was weak without a particular pattern, whereas expression of Bcl-w, p53 and p21(Waf1) proteins was not detected by immunohistochemistry. The results show that spontaneous apoptosis occurs in all male germ cell compartments in humans. Bcl-2 family proteins are distributed preferentially within distinct germ cell compartments suggesting a specific role for these proteins in the processes of differentiation and maturation during human spermatogenesis.