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Consecutive or non-consecutive recurrent miscarriage: is there any difference in carrier status?

Posted: May 20, 2010 at 8:15 am

BACKGROUND

Carrier status of a structural balanced chromosome abnormality is associated with recurrent miscarriage. There is, at present, no evidence of the impact of the sequence of preceding pregnancies on the probability of carrier status. The aim of our study was therefore to examine whether the history of consecutive versus non-consecutive miscarriages in couples with two or more miscarriages has any impact on the probability of carrying a chromosome abnormality.

METHODS

A nested case–control study was performed in six centres for clinical genetics in the Netherlands. Couples referred for chromosome analysis after two or more miscarriages were included: 279 couples with a carrier of a structural chromosomal abnormality and 428 non-carrier couples who served as controls. Univariable and multivariable logistic regression analyses, corrected for known risk factors for carrier status, were performed. The main outcome measure was the probability of carrier status.

RESULTS

Two hundred and fifty-six of 279 (92%) carrier couples and 381 of 428 (89%) non-carrier couples had experienced consecutive miscarriages (P = 0.21). A history of two or three consecutive miscarriages did not alter the probability of carrier status when compared with two [odds ratio (OR) 0.90, 95% confidence interval (CI) 0.48–1.7] or three (OR 0.71, 95% CI 0.39–1.3) non-consecutive miscarriages.

CONCLUSIONS

The sequence of preceding pregnancies is not a risk factor for carrier status. Therefore, couples with miscarriages interspersed with healthy child(ren) should be managed the same as couples with consecutive miscarriages regarding chromosome diagnosis.

Recommendation and review posted by Guinevere Smith

A longitudinal study of contraception and pregnancies in the same women followed for a quarter of a century

Posted: May 20, 2010 at 8:15 am

BACKGROUND

There is a need to improve our understanding of contraceptive use over the long term. The aims of this study were to describe contraceptive use and pregnancies in the same women followed prospectively from 19 to 44 years of age.

METHODS

In 1981, a postal questionnaire about contraception, pregnancies and reproductive health was sent to a random sample (n = 656) of 19-year-old women resident in Gothenburg, Sweden. The responders were contacted again every fifth year.

RESULTS

At 19 years of age, 74% of the women had already used contraception and this increased to 98% at 44 years. Combined oral contraception was the commonest method currently used up to 29 years of age (48/51/22% at 19/24/29 years of age, respectively) and thereafter an intrauterine device (IUD: 34/39/38% at 34/39/44 years of age, respectively). Condom use alone during the 25-year study period was: 14/12/24/21/21/15% and non-use of contraception was: 35/24/26/20/21/26%. The mean number of pregnancies/children increased from 0.2/0.1 at 19 years of age to 3.1/2.1 at 44 years. Women who had been pregnant and women who had not been pregnant ≤19 years of age were compared up to 44 years of age (months of OC use: 69/107, P < 0.01; months of IUD use: 126/91, P < 0.01; 4.2/2.9 pregnancies, P < 0.001; 2.5/2.1 children, P< 0.09).

CONCLUSIONS

Choice of contraception was strongly related to age and parity, and the cumulative total number of pregnancies at 44 years of age, and contraceptive choice was related to age at first pregnancy.

Recommendation and review posted by Guinevere Smith

Predictors of bleeding and user satisfaction during consecutive use of the levonorgestrel-releasing intrauterine system

Posted: May 20, 2010 at 8:15 am

BACKGROUND

Consecutive use of the levonorgestrel-releasing intrauterine system (LNG-IUS) is increasing. However, little is known about factors that predict the bleeding during consecutive use. The objective of this study was to analyse the possible factors which may predict the bleeding pattern during the first year of use of a second LNG-IUS.

METHODS

Fertile-aged women (n = 204) who had used their first LNG-IUS for over 4 years and who opted for a second LNG-IUS were recruited. Bleeding data were reported using 90-day reference periods (RPs) starting from the last 90 days of the first LNG-IUS use (baseline), until the end of the first year of the second LNG-IUS (RPs 1–4).

RESULTS

Demographic factors such as age, parity, body mass index, indication of LNG-IUS use or smoking could not be identified as predictors for bleeding and spotting (B/S). Mean (±SD) number of B/S days was 8.9 (±9.1) at baseline. This increased slightly during RP1 and fell to 6.4 (±8.1) during RP4. Compared with the mean, women with uterine fibroids or a bleeding pattern of >9 days of spotting or any bleeding at RP1 had more B/S days during RP1–4. Although the number of B/S days decreased progressively from RP1 to RP4 in the group with a bleeding pattern of >9 days of spotting or any bleeding at baseline, such a phenomenon was not observed for women with fibroids. The difference for the change in B/S days between women with and without fibroids was statistically significant at RP3 and RP4. A high degree (91.7%) of satisfaction with the bleeding pattern was observed, with amenorrhoeic women being most satisfied.

CONCLUSIONS

Uterine B/S is reduced during consecutive use of the LNG-IUS. Women with uterine fibroids or any bleeding at baseline continued to have more B/S than other women.

Recommendation and review posted by Guinevere Smith

Direct proportional relationship between endometrioma size and ovarian parenchyma inadvertently removed during cystectomy, and its implication on the management of enlarged endometriomas

Posted: May 20, 2010 at 8:15 am

BACKGROUND

The aim of this study was to estimate whether or not the size of an endometrioma is related to the thickness of the ovarian parenchyma inadvertently excised along with the cyst wall.

METHODS

We performed a retrospective study including 35 women who had undergone endometrioma cystectomy, using an ovarian tissue sparing procedure. In total 38 specimens were studied by three pathologists as three women presented bilateral localizations, and all cyst diameters measured at least 30 mm. For each endometrioma, serial sections were performed, and on each section four different sites were randomly chosen to measure the thickness of glandular epithelium and stroma, of subjacent fibrosis, depending on the cyst, and of the ovarian parenchyma removed with the cyst. The diameter of the ovary was measured preoperatively either by MRI or ultrasound, and the area of the internal wall was then calculated. The relationships between the mean thickness of ovarian parenchyma removed and the variables were estimated and a multiple regression model identified independent predictors for ovarian parenchyma thickness.

RESULTS

Adjacent ovarian tissue was found in 37 cases (97%). The mean thickness of ovarian tissue removed was 1173 ± 711 µm and that of the cyst wall was 851 ± 499 µm. The thickness of the ovarian parenchyma removed presented a direct proportional relationship with cyst diameter (P = 0.015), and consequently with cyst wall area (P = 0.032). This relationship with cyst diameter was independent after adjustment on other variables (P = 0.032).

CONCLUSION

Endometrioma cystectomy even though performed with an accurate surgical technique leads to significant ovarian tissue removal, the thickness of which increases proportionally with cyst diameter.

Recommendation and review posted by Guinevere Smith

Large prospective, pregnancy and infant follow-up trial assures the health of 1000 fetuses conceived after treatment with the GnRH antagonist ganirelix during controlled ovarian stimulation

Posted: May 20, 2010 at 8:15 am

BACKGROUND

A concern for new compounds in fertility treatment is the possible risk of perinatal complications or birth defects. To demonstrate long-term safety of ganirelix (GnRH antagonist) treatment in controlled ovarian stimulation (COS), follow-up data on pregnancy and neonatal outcome were analysed for 1000 fetuses (≥16 gestational weeks).

METHODS

Obstetrical and neonatal data on 839 pregnancies, resulting in 969 live born infants after ganirelix treatment were compared with a historical cohort of 753 pregnancies after long GnRH agonist (buserelin) treatment, resulting in 963 live born infants. All treatment cycles were performed in a single fertility centre. The infants were examined at the Universitair Ziekenhuis Brussel using an identical follow-up protocol. Incidence of major malformations (i.e. causing functional impairment or requiring surgical correction) was the primary end-point and was analysed by logistic regression including treatment, age of mother, IVF method and pregnancy type (singleton/multiple) as independent variables.

RESULTS

There were no relevant differences in maternal characteristics, fertilization method and pregnancy and delivery complications between the ganirelix and historical GnRH agonist groups. There were relatively more multiple pregnancies in the historical GnRH agonist group (31.9%) than the ganirelix group (18.7%; P < 0.0001). The groups were comparable with respect to pregnancy loss after 16 weeks gestation. The incidence of major congenital malformations in fetuses with gestational age ≥26 weeks was 5.0% in the ganirelix cohort versus 5.4% in the historical GnRH agonist group (odds ratio 0.94, 95% confidence interval, 0.62–1.42).

CONCLUSION

In terms of neonatal outcome and risk of major malformations, treatment with the GnRH antagonist ganirelix during COS is as safe as traditional GnRH agonists.

ClinicalTrials.gov identifier NCT00724789.

Recommendation and review posted by Guinevere Smith

Altered aquaporin expression in women with polycystic ovary syndrome: hyperandrogenism in follicular fluid inhibits aquaporin-9 in granulosa cells through the phosphatidylinositol 3-kinase pathway

Posted: May 20, 2010 at 8:15 am

BACKGROUND

The present study was designed to evaluate whether the alteration of aquaporin-9 (AQP-9) expression in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS) was associated with the hyperandrogenism in follicular fluid (FF).

METHODS

We recruited infertile women with PCOS (n = 14) and infertile women with tubal blockage (controls, n = 31) for this study. We examined total testosterone (TT), free androgen index (FAI), sex hormone-binding globulin (SHBG), FSH, LH and estradiol in FF. Real-time PCR and western blotting were performed to assess AQP-9 expression in GCs, including effects of dihydrotestosterone (DHT) in vitro.

RESULTS

AQP-9 protein was localized in the nucleus, cytoplasm and cell membrane of the human GCs. The TT, FAI and LH levels were all higher, and SHBG levels lower, in the FF of women with PCOS versus controls (P = 0.0145, 0.0001, 0.0191, 0.0001, respectively). AQP-9 mRNA level in GCs of patients with PCOS was tightly correlated with the TT, SHBG levels and FAI in FF (P = 0.0020, 0.0001, 0.0020, respectively). In vitro, DHT (10–9 mol/l) decreased AQP-9 mRNA (lowest at 12 h) and protein levels in control GCs (P = 0.0005, 0.0247, respectively). The inhibitory effect of DHT on AQP-9 mRNA was attenuated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor (P = 0.0013). Fifty micromolar 4-(hydroxymercuri) benzoic acid sodium salt (PMB) and 10–9 mol/l DHT blunted the swelling of GCs in hypotonic medium, respectively (P = 0.0350, 0.0027).

CONCLUSION

Hyperandrogenism in FF of women with PCOS inhibited AQP-9 in GCs through the PI3K pathway.

Recommendation and review posted by Guinevere Smith


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