Mental health of mothers and fathers of twins conceived via assisted reproduction treatment: a 1-year prospective study.

BACKGROUND: Although twin deliveries after assisted reproduction treatment (ART) are common, the mental health of the parents has scarcely been addressed. Therefore, we evaluated the psychological well-being of ART and spontaneously conceiving parents of twins and singletons. Furthermore, the impact of parity and children's health-related factors on mental health was evaluated. METHODS: We conducted a prospective longitudinal questionnaire study among ART parents of 91 pairs of twins and of 367 singletons and on control parents of 20 pairs of twins and of 379 singletons in the 2nd trimester of pregnancy (T1), and when the children were 2 months (T2) and 1-year old (T3). Symptoms of depression and anxiety, sleeping difficulties and social dysfunction were addressed via a questionnaire. The effects of parity and child-related factors were assessed at T2. RESULTS: At T1, ART mothers of twins showed fewer symptoms of depression than control mothers of twins (P < 0.05). At T2, both ART and control mothers of twins had more symptoms of depression and anxiety than all mothers of singletons (F = 5.20, P < 0.05 and F = 3.93, P < 0.05, respectively). At T3, both ART and control mothers of twins continued to report more symptoms of depression than the mothers of singletons (F = 10.01, P < 0.01), but a difference in anxiety symptoms was seen only in the control group. All fathers had similar mental health at T1. At T2, ART and control fathers of twins reported more symptoms of depression (F = 4.15, P < 0.05) and social dysfunction than fathers of singletons. At T3, both ART and control fathers of twins had more symptoms of depression (F = 4.29, P < 0.05) and anxiety (F = 5.40, P < 0.05) than fathers of singletons. Control fathers of twins had more sleeping difficulties than fathers of singletons (F = 6.66, P < 0.01). Parity did not differently affect parental mental health at T2 in the study groups. Prematurity did not affect maternal mental health, but it had a negative impact on control fathers' social dysfunction (F = 3.34, P < 0.05). CONCLUSIONS: Twin parenthood, but not ART, has a negative impact on the mental health of mothers and fathers during the transition to parenthood. ART parents' mental health was not affected by parity or children's health-related factors.

Infertility treatment and marital relationships: a 1-year prospective study among successfully treated ART couples and their controls.

BACKGROUND: Evidence about the effects of infertility and assisted reproduction technique (ART) on marital relationships is discrepant. Here, we examined the impact of ART on marital relationships. The roles of life stressors, infertility and treatment characteristics in predicting marital relations were also evaluated. SUBJECTS: 367 couples with singleton IVF/ICSI pregnancies. CONTROLS: 379 couples with spontaneous singleton pregnancies. Women and men were assessed when the child was 2 months (T2) and 12 months old (T3). They further reported stressful life events at T2 and depression in pregnancy. RESULTS: No between-group differences were found in marital satisfaction and dyadic cohesion. Dyadic consensus deteriorated from T2 to T3 only among control women. Sexual affection was low among control men at T2 and stressful life events decreased it further. Depression during pregnancy predicted deteriorated marital relations only in control couples. Several unsuccessful treatment attempts were associated with good dyadic consensus and cohesion among ART women. Spontaneous abortions and multiple parity predicted poor marital satisfaction in ART women, whereas long duration of infertility and multiple parity predicted poor marital relations in ART men. CONCLUSIONS: Successful ART does not constitute a risk for marital adjustment. The shared stress of infertility may even stabilize marital relationships.

Fear of childbirth and pregnancy-related anxiety in women conceiving with assisted reproduction.

OBJECTIVE: To compare the prevalence and predictors of severe fear of childbirth and pregnancy-related anxiety in groups of assisted reproduction treatment (ART) and spontaneously conceiving women with singleton pregnancies. METHODS: The ART group (n = 367, nulliparous 260) represented a cohort from five Finnish infertility clinics in 1999. The control group (n = 379, nulliparous 135) was enrolled in this study by consecutive sampling the same year. Fear of childbirth was assessed by means of the revised version of the Fear-of-Childbirth Questionnaire and pregnancy-related anxiety by means of the Pregnancy Anxiety Scale at gestational week 20 +/- 3.2 (mean+/-standard deviation). RESULTS: The frequency of severe fear of childbirth and anxiety (classified as total scores in the 90th percentile or higher in the revised Fear of Childbirth Questionnaire and Pregnancy Anxiety Scale) did not differ between the groups. Nulliparity was associated with more frequent severe anxiety only in the controls. In nulliparous participants, a partnership of more than 5 years decreased the risk of severe fear of childbirth (odds ratio 0.3, 95% confidence interval 0.2-0.7). In the nulliparous ART group, a long duration of infertility (7 or more years) increased the risk of severe fear of childbirth (odds ratio 4.4, 95% confidence interval 1.2-16.9). CONCLUSION: Women conceiving after ART do not experience severe fear of childbirth or pregnancy-related axiety more often than spontaneously conceiving controls. However, a long duration of infertility is an independent risk factor regarding severe fear of childbirth. LEVEL OF EVIDENCE: II-2.

Impact of infertility characteristics and treatment modalities on singleton pregnancies after assisted reproduction.

Obstetric and neonatal outcomes of assisted reproduction and control singletons were evaluated after taking into account treatment characteristics and infertility background. The elective single embryo transfer (eSET) group (n = 45) was compared with the compulsory single embryo transfer (cSET; n = 52), double embryo transfer (DET; n = 227) and control (n = 304) groups. Infertility-related prognostic factors for neonatal outcomes were also analysed. Data were collected with structured questionnaires at gestational week 20 and 8 weeks after delivery. Spontaneous onset of delivery was more typical of the eSET group than of cSET and DET groups (68.9 versus 52.0%, P = 0.02). Mean (+/-SD) gestation at birth (39.3 +/- 1.6 weeks) and mean birth weight (3,470 +/- 505 g) of eSET singletons were comparable with other assisted reproduction groups, but gestational duration was lower than in the eSET group than in the control group (39.9 +/- 1.4; P < 0.05). However, numbers of preterm births and low birth weight infants were similar between groups. History of induced abortion increased risk of preterm birth (OR 4.5 and 95% CI 1.2-17.1) in assisted reproduction singletons. A small though clinically unimportant difference in gestational age at birth and birth weight between assisted reproduction and control singletons was found regardless of the number of embryos transferred.

The impact of successful assisted reproduction treatment on female and male mental health during transition to parenthood: a prospective controlled study.

BACKGROUND: The dynamics of mental health during the transition to parenthood have not been a focus of research. Our prospective longitudinal study was designed to reveal whether there are differences in mental health during the transition to parenthood between parents undergoing treatment with assisted reproduction techniques (ART) and those who conceive spontaneously. STUDY GROUP: 367 couples with a singleton ART pregnancy using their own gametes. CONTROL GROUP: 379 couples with a spontaneous singleton pregnancy. Men and women separately filled in questionnaires including the General Health Questionnaire: at the 18th-20th week of pregnancy, 2 months postpartum and 1 year postpartum (T3). The effect of social and child-related factors on mental health was examined. RESULTS: ART women had fewer depressive symptoms during pregnancy than controls, but at T3 their depressive symptoms were at the same level as seen in controls. Anxiety symptoms increased among control but not among ART women across the transition. ART men reported generally fewer mental health symptoms than their controls. Social and child-related stressors had negative impacts on mental health changes among control couples, whereas no impact was found among ART couples. CONCLUSIONS: Successful ART did not predict mental health problems during the transition to parenthood. Moreover, ART couples' mental health was remarkably resistant to social and child-related stress during the transition to parenthood.

One versus two embryo transfer after IVF and ICSI: a randomized study.

BACKGROUND: The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time. METHODS: A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups. RESULTS: The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group. CONCLUSIONS: Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided.

Comparison of two recombinant follicle-stimulating hormone preparations in in-vitro fertilization: a randomized clinical study.

A randomized comparison of two recombinant human follicle-stimulating hormone (recFSH) preparations (Gonal-F and Puregon) in ovarian stimulation for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was carried out at the Infertility Clinic of the Family Federation of Finland. A total of 348 women (aged 22-43 years) suffering from infertility due to miscellaneous causes was recruited. Of these, 344 underwent stimulation using equal starting doses (150 IU/day: Gonal-F n = 164, Puregon n = 158 or 300 IU/day: Gonal-F n = 8, Puregon n = 14) after down-regulation with intranasal buserelin from the mid-luteal phase. Similar clinical pregnancy rates were achieved with both preparations; 33.5% per cycle and 37.4% per embryo transfer (24.5% one-embryo and 75.5% two-embryo transfers, n = 147) with Gonal-F (150 IU/day) and 32.9% per cycle and 36.4% per embryo transfer (30.1% one-embryo and 69.9% two-embryo transfers, n = 145) with Puregon (150 IU/day). The ongoing cumulative pregnancy rates after frozen-thawed embryo transfer were 35.4% with Gonal-F and 37.7% with Puregon. Six cycles were cancelled because of a low response (three in each group). Similar numbers of oocytes were obtained in both groups; 13.0 with 150 IU/day and 6.1 with 300 IU/day Gonal-F, and 12.4 with 150 IU/day and 7.1 with 300 IU/day Puregon. The fertilization and cleavage rates and the incidence of moderate or severe ovarian hyperstimulation syndrome (Gonal-F, 2.0% and Puregon, 0.7%) were also similar. Gonal-F and Puregon were equally and highly effective in stimulation for IVF and ICSI.

Elective transfer of one embryo results in an acceptable pregnancy rate and eliminates the risk of multiple birth.

To avoid multiple pregnancies without compromising pregnancy rates (PR) is a challenge in assisted reproduction. We have compared pregnancy results among 74 elective one-embryo transfers (group 2) and 94 transfers where only one embryo was available (group 1). All the fresh embryo cycles during 1997 in two clinics in Helsinki were analysed, and cumulative PR among these couples after frozen-thawed embryo transfers up to June 1998 were counted. In group 2, where at least two embryos were available for transfer, and only one was transferred on day 2 or 3, the PR per embryo transfer was 29.7%. In group 1, the PR per embryo transfer was 20.2%. In group 2, the cumulative PR after frozen-thawed embryo transfers was 47.3% per oocyte retrieval. Over the same time, 742 two-embryo transfers were carried out. The PR per embryo transfer was 29.4% in these subjects, but 23.9% of these pregnancies were twins. The implantation rates, as well as the PR, were highest when the embryos were at the four- to five-cell stage on day 2 (35.8 versus 9.7% compared with the two- to three-cell stage, P < 0.001) or at the six- to eight-cell stage on day 3 (45.5%). The PR per embryo transfer was higher when a grade 1 or 2 embryo was transferred compared with a grade three embryo (34. 0 and 26.7% versus 8.8% respectively, P < 0.05). In women 35 years or younger, the PR per elective one-embryo transfer was 32.8%. The corresponding figure in women older than 35 years was 18.8%. On the basis of these results, elective one-embryo transfer can be highly recommended, at least in subjects who are younger than 35 years of age, and who have grade one or grade two embryos available for transfer.

Activin B: detection by an immunoenzymometric assay in human serum during ovarian stimulation and late pregnancy.

A recently developed immunoenzymometric assay for activin B has been characterized further by measurement during ovarian stimulation and pregnancy. The assay is based on a monoclonal anti-peptide antibody, anti-betaB(101-115). In addition to quantitative analyses, the antibody has been used for immunohistochemical localization of the activin betaB-subunit in human term placenta. Serum samples obtained from patients suffering from tubal factor infertility who were admitted for in-vitro fertilization (IVF) treatment protocols or from patients with proven fertility who were admitted for laparoscopic tubal ligation were collected. The aim was to correlate serum activin B concentrations with other parameters during IVF and with phases of the menstrual cycle. Serum samples obtained from healthy pregnant volunteers were studied to correlate activin B concentrations with clinical parameters. During the IVF treatment protocols, activin B was detectable in all patients studied, and a significant negative correlation was observed between serum activin B and oestradiol concentrations. On the other hand, no significant difference was observed in activin B concentrations when serum samples obtained from patients at different phases of the menstrual cycle were compared, and low concentrations of activin B were observed in the samples obtained from these patients. During pregnancy, a positive correlation was observed between serum activin B concentrations and gestational age. In immunohistochemical analyses of human placental tissue obtained from healthy parturients, the activin betaB-subunit was present in trophoblast, amniotic epithelial and Hofbauer cells. The results suggest a potential clinical application in female reproductive medicine for serum activin B measurements.

Infertility and coeliac disease.

BACKGROUND: Coeliac women may suffer from gynaecological and obstetric complications. It is possible that these complications are the first symptom of coeliac disease. AIMS: To investigate the occurrence of subclinical coeliac disease in patients with infertility or recurrent miscarriages. SUBJECTS: Women of reproductive age who were attending the hospital because of either primary or secondary infertility, or two or more miscarriages. Women undergoing sterilisation served as control subjects. METHODS: The diagnostic investigation for infertility included the endocrine status, diagnostic laparoscopy, investigation of tubal patency, postcoital test, and semen analysis of the partner. Circulating antibodies against IgA class reticulin and gliadin were used in screening for coeliac disease. In positive cases, the diagnosis was confirmed by small bowel biopsy specimens. RESULTS: Four (2.7%) of 150 women in the infertility group, and none of the 150 control subjects were found to have coeliac disease (p = 0.06). All four women with coeliac disease suffered from infertility of unexplained origin. Altogether 98 women had no discoverable reason for infertility. Thus, in this subgroup the frequency of coeliac disease was 4.1% (four of 98), the difference from the control group being statistically significant (p = 0.02). None of the coeliac women had extensive malabsorption, but two had iron deficiency anaemia. One women with coeliac disease has had a normal delivery. None of the 50 women with miscarriage had coeliac disease. CONCLUSION: Patients having fertility problems may have subclinical coeliac disease, which can be detected by serological screening tests. Silent coeliac disease should be considered in the case of women with unexplained infertility.

Outcome of pregnancies in women with treated or untreated hyperprolactinemia.

The outcome of 103 pregnancies in 64 women with constant hyperprolactinemia was evaluated. Seventy-eight pregnancies had been induced with bromocriptine and 25 occurred without any treatment. In all, 66% of the pregnancies ended in delivery, 17% in miscarriage, 10% in tubal pregnancy and 7% in induced abortion. The pregnancy of women with untreated hyperprolactinemia was more frequently ectopic when compared to those in women treated by bromocriptine. Obstetric complications as well as signs of tumoral enlargement during pregnancy were rare in hyperprolactinemic women treated or untreated with bromocriptine. Untreated hyperprolactinemia as a risk factor in tubal pregnancy is proposed.

Lymphocyte beta 2-adrenoceptor density during menstrual cycle and pregnancy, in delivery and puerperium.

Lymphocyte beta 2-adrenoceptor density was determined in 11 women during the normal menstrual cycle and 15 women during normal pregnancy. No significant difference in lymphocyte beta 2-adrenoceptor density was established in this follow-up study during the menstrual cycle or pregnancy. Lower lymphocyte beta 2-adrenoceptor density was established just after delivery and in puerperium compared with that during pregnancy. It is likely that the high catecholamine concentration during parturition together with the duration of labour and delivery caused down-regulation of the beta 2-adrenoceptors. In puerperium the irregular day-rhythm and the stress of caring for the newborn may also have an effect.

Endocrine status and growth after malignancy treated in childhood or adolescence.

Six girls and three boys, asymptomatic after treatment for acute lymphoblastic leukemia (ALL) or endodermal sinus tumor (EST), were investigated for endocrine status and growth. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), testosterone binding capacity (TeBC), 17 alpha-hydroxyprogesterone (17-OHP), progesterone (P), thyroxine (T4), thyroid stimulating hormone (TSH), and cortisol were measured, and pubertal stage and bone age were determined. Growth was evaluated according to accepted curves for height and weight. Four of the girls had normal pubertal development, with serum FSH, LH, and E2 levels correlating to the phase of the menstrual cycle. Only one of the girls had ovulatory cycles (increase in P level). The girl treated for EST by abdominal irradiation had gonadal failure, with postmenopausal serum levels of FSH, LH, and E2. Her karyotype was normal. One of the girls was still prepubertal. None of them was hyperandrogenemic. One boy who was treated with bone marrow transplantation and total body irradiation had gonadal failure. One boy was still prepubertal, and the third boy showed normal pubertal maturation and normal serum FSH, LH, and T levels. All the patients except the boy treated with bone marrow transplantation and irradiation were normoprolactinemic; in addition, all had normal thyroid and adrenal function. Height and weight curves were normal in seven of the patients after the cancer therapy. The girl with EST had finished her growth before the irradiation therapy began. The boy treated with bone marrow transplantation and irradiation failed to exhibit further growth after beginning leukemia therapy at the age of 9.3 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Skinfold thickness and long-term post-menopausal hormone therapy.

Skinfold thickness was measured in 130 post-menopausal women treated with long-term hormone therapy. One group of 50 women took oestradiol valerate 2 mg/day for 3 wk out of 7, a second group comprising 19 women received oestriol succinate 2 mg/day and the remaining group of 61 women used oestradiol valerate 2 mg/day combined sequentially with norgestrel 0.5 mg/day. The duration of treatment in these groups was 6.3 +/- 0.4, 6.4 +/- 0.4 and 3.3 +/- 0.3 yr, respectively. The control group was made up of a further 89 post-menopausal women. The skinfold thickness in all the treated groups was significantly greater than that in the controls.

Long-term post-menopausal hormone therapy and serum HDL-C, total cholesterol and triglycerides.

Serum high-density lipoprotein cholesterol (HDL cholesterol), total cholesterol and triglyceride concentrations were determined in 158 post-menopausal women following long-term oral hormone replacement therapy. Oestradiol valerate (2 mg/day) was taken by 53 of the women and oestriol succinate (2 mg/day) by 42 others. The duration (means +/- SD) of the oestradiol valerate therapy was 6.4 (+/- 2.9) yr and of the oestriol succinate therapy 6.4 (+/- 2.3) yr. The remaining 63 women received oestradiol valerate (2 mg/day) combined sequentially with norgestrel (0.5 mg/day). The average duration of treatment with this combination was 3.3 (+/- 2.4) yr. The control group comprised 100 post-menopausal women who received no hormone therapy whatsoever. The HDL cholesterol levels in the women receiving oestradiol valerate were higher than those in the controls (P = 0.001) and in the women on oestradiol valerate plus norgestrel therapy (P less than 0.001). The HDL cholesterol levels in the oestriol succinate group did not differ significantly from those in the controls. The women receiving oestradiol valerate in combination with norgestrel had lower serum HDL cholesterol concentrations than the controls (P less than 0.05). Serum total cholesterol and triglyceride concentrations did not differ in either oestrogen group from those in the controls, but were lower in the oestradiol valerate-plus-norgestrel group than in the controls (P less than 0.001). There were no differences in serum total oestrogen, oestrone, oestradiol and oestriol levels between control subjects with normal HDL cholesterol concentrations and those with low concentrations.

The vaginal absorption of oestrogens in post-menopausal women.

Serum E1, E2 and E3 concentrations and E2/E1 ratio were measured after vaginal application of conjugated oestrogens, micronized 17 beta-oestradiol and oestriol. 2.4 mg of conjugated oestrogens caused a prompt elevation in the serum E1 concentration; the E2 level changed only slightly. After vaginal application of 2 mg micronized 17 beta-oestradiol the main serum oestrogen is E2 and the conversion of E2 to E1, as in oral administration, does not occur. A significant elevation in the serum E3 concentration was noted 2 h after the vaginal application of 0.5 mg oestriol. The E2/E1 ratio changed little after the application of conjugated oestrogens but increased considerably after the vaginal administration of 2 mg micronized 17 beta-oestradiol.