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Category Archives: Human Reproduction

Interferon gamma contributes to preimplantation embryonic development and to implantation site structure in NOD mice

BACKGROUND

Pre-eclampsia, a syndrome usually accompanied by incomplete spiral arterial modification, occurs at an increased frequency in diabetic women. Hyperglycemia in non-obese type 1 diabetic (NOD) mice impairs gestational spiral arterial remodeling despite high local levels of interferon gamma (Ifng), the triggering cytokine in mice. Pregnancies in NOD.Ifng–/– mice were assessed to investigate this issue.

METHODS

Fecundity was assessed using the breeding history, flushing of preimplantation embryos and histological and morphometric studies of implantation sites in normoglycemic (n-) and hyperglycemic (d-) females of NOD.Ifng–/– and NOD genotypes.

RESULTS

NOD.Ifng–/– but not NOD mice are mostly infertile. In NOD.Ifng–/–, copulation often does not result in a post-implantation pregnancy. Defective fertilization and delayed preimplantation development limit n-NOD.Ifng–/– fertility, and both mechanisms are exacerbated by hyperglycemia. At mid-gestation, implantation sites in n-NOD.Ifng–/– and n-NOD mice are histologically similar. However, in d-NOD.Ifng–/–, there is minimal development of spiral arteries, hypertrophy of the myometrial region containing uterine Natural Killer (uNK) cells and a deficit in cytoplasmic granule formation in the uNK cells.

CONCLUSIONS

Ifng contributes to the success of fertilization and to the rate of preimplantation mouse embryo development in normogylcemic and hyperglycemic pregnancies. A physiological role for this cytokine in human preimplantation development merits investigation.

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Men’s experiences of infertility and infertility treatment 5 years after diagnosis of male factor infertility: a retrospective cohort study

BACKGROUND

The aim of this study was to describe the perceptions of infertile men regarding the impact of infertility on their intimate relationships, their experience of treatment and their sources of information and support.

METHODS

A cross-sectional survey of a consecutive cohort of men diagnosed 5 years earlier as infertile at Melbourne IVF and the Royal Women's Hospital Reproductive Services, Melbourne was conducted. Study-specific questions assessed the impact of male factor infertility on the intimate relationships, their perceived quality of infertility-related health care and their preferred sources of infertility-related information and personal support and the effectiveness of these.

RESULTS

The response rate was 41% (112/276). Male factor infertility was reported to have had a negative impact on the intimate partner relationship by 25% of men, and 32% reported a negative effect on their sexual satisfaction. Satisfaction with medical care and clinic information was high and not influenced by the outcome of the treatment. Clinic-provided information and discussion with clinic staff were the most strongly preferred sources of information, and the partner and clinic staff were the most valued sources of personal support. Very few men found support groups useful and less than half confided in friends.

CONCLUSIONS

The findings suggest that for a significant subgroup of men, male factor infertility affects their intimate relationship negatively. Wider sources of social support are not used by infertile men as they rely predominantly on clinic-provided information and support. This indicates that psychologically informed supportive clinical care is particularly important for men diagnosed as infertile.

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Serum inhibin B concentrations in pubertal boys conceived by ICSI: first results

BACKGROUND

Currently, no published data exist about the gonadal function of children born after ICSI. To evaluate potential risk of testicular seminal dysfunction in boys born to fathers with compromised spermatogenesis, serum inhibin B (as a marker for spermatogenesis) was assessed.

METHODS

We recruited 50 pubertal adolescents from the oldest cohort of infants born following ICSI. Cross-sectional serum inhibin B levels of all 50 ICSI adolescents, and longitudinal serum inhibin B (assessed at 8 and 14 years) in 25 boys, are reported.

RESULTS

A statistically significant increase in inhibin B levels was observed between 8 (mean 69 ng/l, SD ± 35) and 14 years (mean 145 ng/l, SD ± 41; P < 0.001). In three quarters of the ICSI boys an increase in serum inhibin B levels of at least 30% between 8 and 14 years was observed. In all but 4 of the 14-year-old ICSI boys serum inhibin B was normal. Serum inhibin B levels in boys from fathers with severe oligozoospermia did not differ from concentrations in boys from fathers without severe oligozoospermia (154 ± 51 and 142 ± 47 ng/l, respectively; P = 0.4).

CONCLUSIONS

The majority of ICSI boys have a significant increase in serum inhibin B, attaining normal values for pubertal status at the age of 14 years. ICSI adolescents from fathers with severely compromised spermatogenesis do not have lower inhibin B levels than those with fathers with normal spermatograms. Further follow-up of the spermatogenic potential of ICSI teenagers up to young adulthood is mandatory to confirm a normal reproductive capacity.

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Fertility and pregnancy outcomes following conservative treatment for placenta accreta

BACKGROUND

The aim of this study was to estimate the fertility and pregnancy outcomes after successful conservative treatment for placenta accreta.

METHODS

This retrospective national multicenter study included women with a history of conservative management for placenta accreta in French university hospitals from 1993 through 2007. Success of conservative treatment was defined by uterine preservation. Data were retrieved from medical files and telephone interviews.

RESULTS

Follow-up data were available for 96 (73.3%) of the 131 women included in the study. There were eight women who had severe intrauterine synechiae and were amenorrheic. Of the 27 women who wanted more children, 3 women were attempting to become pregnant (mean duration: 11.7 months, range: 7–14 months), and 24 (88.9% [95% confidence interval (CI), 70.8–97.6%]) women had had 34 pregnancies (21 third-trimester deliveries, 1 ectopic pregnancy, 2 elective abortions and 10 miscarriages) with a mean time to conception of 17.3 months (range, 2–48 months). All 21 deliveries had resulted in healthy babies born after 34 weeks of gestation. Placenta accreta recurred in 6 of 21 cases [28.6% (95% CI, 11.3–52.2%)] and was associated with placenta previa in 4 cases. Post-partum hemorrhage occurred in four [19.0% (95% CI, 5.4–41.9%)] cases, related to placenta accreta in three and to uterine atony in one.

CONCLUSIONS

Successful conservative treatment for placenta accreta does not appear to compromise the patients' subsequent fertility or obstetrical outcome. Nevertheless, patients should be advised of the high risk that placenta accreta may recur during future pregnancies.

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Embryo and uterine influences on IVF outcomes: an analysis of a UK multi-centre cohort

BACKGROUND

In order to optimize IVF strategies, particularly with the use of single embryo transfer, good predictive models are required. Here, we develop a model to allow such prediction, and the structure of the models point to more general conclusions about the mode of action of prognostic factors.

METHODS

Anonymized data from consecutive embryo transfers in five IVF centres in the UK for the 2000–2005 period were extracted and the morphological grade based on common scoring criteria was included. There were 16 096 (12 487 fresh and 3609 frozen) transfers, for 8775 couples, available for analysis. Live birth data were fitted to a model with separate sub-models for embryo and recipient effects [the ‘Embryo-Uterus’ (EU) model]. All covariates were included, with sub-model selection using Akaike's information criterion.

RESULTS

Age, number of embryos created, attempt number, previous history of pregnancy, duration of infertility, day of transfer and tubal diagnosis were all identified as significant prognostic factors, along with embryo grade and growth rate. Frozen transfers were substantially less likely to lead to a live birth with odds ratios of 1/3 to 1/2 compared with fresh transfers, with no evidence of differential loss for any particular patient group. Age acts predominantly through the embryo component with only a weak effect on the uterus. The embryo number, attempt number, previous pregnancies and duration of infertility act predominantly through the uterine environment. Both sub-models show significant heterogeneity between centres.

CONCLUSIONS

The EU modelling framework has generated a model for predicting outcomes of embryo-transfer procedures, subject to the limitations of routinely collected data. With this large data set, the model allows identification of factors that act specifically on embryo viability or maternal receptivity. Variability in the two components between centres with similar overall outcomes suggests scope for further optimization of IVF treatment.

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Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial

BACKGROUND

Clomiphene citrate (CC) is the first-line therapy for the induction of ovulation in infertile women with polycystic ovary syndrome (PCOS), but ~20% of patients are unresponsive. The aim of the current study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and hypocaloric diet increases the probability of ovulation after CC in overweight and obese CC-resistant PCOS patients.

METHODS

A cohort of 96 overweight and obese CC-resistant PCOS patients was enrolled consecutively in a three-arm randomized, parallel, controlled, assessor-blinded clinical trial. The three interventions were: SET plus hypocaloric diet for 6 weeks (Group A); 2 weeks of observation followed by one cycle of CC therapy (Group B); and SET plus hypocaloric diet for 6 weeks, with one cycle of CC after the first 2 weeks (Group C). The primary end-point was the ovulation rate. Other reproductive data, as well as anthropometric, hormonal and metabolic data, were also collected and considered as secondary end points.

RESULTS

After 6 weeks of SET plus hypocaloric diet, the ovulation rate was significantly (P =0.008) higher in Group C [12/32 (37.5%)] than in Groups A [4/32 (12.5%)] and B [3/32 (9.4%)] with relative risks of 3.9 [95% confidence interval (CI) 1.1–8.3; P = 0.035] and 4.0 (95% CI 1.2–12.8; P = 0.020) compared with Groups A and B, respectively. Compared with baseline, in Groups A and C, a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes was observed. In the same two groups, the insulin sensitivity index was significantly (P < 0.05) better than that in Group B.

CONCLUSIONS

In overweight and obese CC-resistant PCOS patients, a 6-week intervention of SET and a hypocaloric diet was effective in increasing the probability of ovulation under CC treatment.

The study was registered at Clinicaltrials.gov: NCT0100468.

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