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Category Archives: Human Reproduction

Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls

BACKGROUND

There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking.

METHODS

Observational studies published 1959–2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers. ORs adjusted for potential confounders were extracted (e.g. maternal age and alcohol), otherwise unadjusted estimates were used. One hundred and seventy-two articles were used in the meta-analyses: a total of 173 687 malformed cases and 11 674 332 unaffected controls.

RESULTS

Significant positive associations with maternal smoking were found for: cardiovascular/heart defects [OR 1.09, 95% confidence interval (CI) 1.02–1.17]; musculoskeletal defects (OR 1.16, 95% CI 1.05–1.27); limb reduction defects (OR 1.26, 95% CI 1.15–1.39); missing/extra digits (OR 1.18, 95% CI 0.99–1.41); clubfoot (OR 1.28, 95% CI 1.10–1.47); craniosynostosis (OR 1.33, 95% CI 1.03–1.73); facial defects (OR 1.19, 95% CI 1.06–1.35); eye defects (OR 1.25, 95% CI 1.11–1.40); orofacial clefts (OR 1.28, 95% CI 1.20–1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18–1.36); gastroschisis (OR 1.50, 95% CI 1.28–1.76); anal atresia (OR 1.20, 95% CI 1.06–1.36); hernia (OR 1.40, 95% CI 1.23–1.59); and undescended testes (OR 1.13, 95% CI 1.02–1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85–0.95) and skin defects (OR 0.82, 0.75–0.89). For all defects combined the OR was 1.01 (0.96–1.07), due to including defects with a reduced risk and those with no association (including chromosomal defects).

CONCLUSIONS

Birth defects that are positively associated with maternal smoking should now be included in public health educational materials to encourage more women to quit before or during pregnancy.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

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Defining infertility–a systematic review of prevalence studies

BACKGROUND

Existing definitions of infertility lack uniformity, rendering comparisons in prevalence between countries or over time problematic. The absence of an agreed definition also compromises clinical management and undermines the impact of research findings. The aim of this study was to perform a systematic review of the literature to determine how infertility has been defined in prevalence studies and to come up with suggestions for a feasible and clinically relevant definition.

METHODS

MEDLINE, EMBASE, CINAHL and Cochrane Database of Systematic Reviews were searched for relevant population-based prevalence studies published between 1975 and 2010.

RESULTS

A total of 39 articles were included in the current review. The results highlight the heterogeneity of criteria used to define infertility and critical differences between demographic and epidemiological definitions. Demographers tend to define infertility as childlessness in a population of women of reproductive age, while the epidemiological definition is based on ‘trying for’ or ‘time to’ a pregnancy, generally in a population of women exposed to the risk of conception. There is considerable variation in terms of the duration of ‘trying for pregnancy’, the age of women sampled and their marital or cohabitation status. This leads to inconsistencies in determining the numerator and denominator used to calculate the prevalence of infertility.

CONCLUSIONS

There is a need for an agreed definition for infertility. We suggest a clinically relevant definition based on the duration of trying for pregnancy coupled with female age.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

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Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery

BACKGROUND

Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept®) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS).

METHODS

Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed.

RESULTS

Of 498 patients randomized, 330 were evaluable (160 LRS – 75% myomectomy/25% endometriotic cysts; 170 Adept – 79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related.

CONCLUSIONS

The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

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Oncologic and reproductive outcomes of cystectomy compared with oophorectomy as a treatment for borderline ovarian tumours

BACKGROUND

The aim of this study was to compare the oncologic and reproductive outcomes of patients with borderline ovarian tumours (BOTs) who were treated with cystectomy or unilateral salpingo-oophorectomy (USO).

METHODS

The medical records of patients with BOTs who were treated between 1997 and 2009 were reviewed retrospectively. The recurrence rates were compared between the USO and cystectomy groups. The reproductive outcomes were assessed by telephone interviews.

RESULTS

Patients with BOTs underwent a USO (n= 117) or cystectomy (n= 38). There were 12 patients who had recurrences: 1 patient had an invasive recurrence and 11 had borderline recurrences. The recurrence rate in the USO group (6.0%) was lower than in the cystectomy group (13.2%); however, this difference was not statistically significant (P= 0.110). All of the patients with recurrences were successfully treated with surgery and there was no clinical evidence of disease. Of the 116 patients contacted by telephone, 113 (97.4%) resumed menstruation following the surgery, and 45 of the 52 patients (86.5%) who attempted to conceive had successful pregnancies. USO (89.2%), like cystectomy (85.7%), resulted in excellent pregnancy rates for patients with BOTs.

CONCLUSIONS

A USO is an appropriate treatment for women with BOTs who wish to preserve fertility. However, a cystectomy is a satisfactory fertility-sparing therapy when a cystectomy is the only surgical option.

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The effect of modified quarter laser-assisted zona thinning on the implantation rate per embryo in frozen/vitrified-thawed/warmed embryo transfer cycles: a prospective randomized controlled trial

BACKGROUND

Freezing/vitrifying and thawing/warming of embryos may impair the successful hatching process of the embryo out of its zona pellucida (ZP) and its following implantation into the uterus. Theoretically, assisted hatching (AH) may facilitate the hatching process and subsequently increase implantation rates (IRs).

METHODS

In this prospective randomized controlled trial (RCT), the hypothesis was tested that the IR per embryo transferred is higher after transfer (ET) of frozen/vitrified-thawed/warmed embryos with thinned ZP after AH by modified quarter laser-assisted zona thinning (mQLAZT) when compared with ET of frozen/vitrified-thawed/warmed embryos without mQLAZT. Patients with frozen/vitrified embryos were randomized at the time of thawing/warming to a study group (with mQLAZT) or a control group (without mQLAZT). After thawing/warming, embryos were kept in culture for 24h, and mQLAZT was performed prior to ET.

RESULTS

A total of 647 thawing cycles were randomized to either the mQLAZT group (n = 324) or the control group (n = 323). Reproductive outcome data were available for 302 cycles in the mQLAZT group and 317 cycles in the control group. Transfer could be performed in 73.5% and in 71.9% of the thawing/warming cycles in the mQLAZT group and the control group (P = 0.78), respectively. No significant differences were observed between the mQLAZT group and the control group for the IR [13.3%; 15.6%; rate ratio 0.85; 95% confidence interval (CI), 0.596–1.224], the ongoing IR (10.5 and 13.5%, P = 0.25) and the live birth rate [10.5%;13.3%; rate ratio 0.79; (95% CI), 0.530–1.189] per embryo transferred.

CONCLUSIONS

In this RCT, mQLAZT did not improve the IR per embryo transferred in frozen/vitrified-thawed/warmed embryo transfer cycles.

ClinicalTrials.govID NCT00593775.

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A pragmatic RCT of conventional versus increased concentration sucrose in freezing and thawing solutions for human embryos

BACKGROUND

Intact frozen-thawed embryos have a greater potential than damaged embryos to establish successful pregnancies. This study aimed to determine whether elevated concentrations of sucrose during freezing would increase the proportion of patients with ≥50% of embryos intact after thawing (primary outcome), and improve clinical outcome.

METHODS

In a two arm, parallel group, pragmatic trial, IVF/ICSI couples were randomized prospectively to have their supernumerary embryos frozen in a medium containing 0.1 M sucrose (control; n = 99) or 0.3 M sucrose (intervention; n = 102).

RESULTS

More control (74/99) than intervention (63/102) couples had at least one embryo thawed (P = 0.07). Significantly more (P = 0.005) intervention (53/63) than control (45/74) couples had ≥50% of embryos intact. Freezing in a medium containing 0.3 M sucrose increased by 3.4-fold [95% confidence interval (CI) (1.45, 7.82)] the likelihood of a couple having ≥50% of their embryos intact. In the fresh cycle, live birth rate per transfer was similar in the control (35/95) and intervention (36/93) groups (P = 0.91). More control (19/63) than intervention (9/59) couples had a live birth after frozen embryo transfer (P = 0.08). When fresh and frozen cycles were combined, fewer intervention (n = 102) than control (n = 99) couples had at least one live birth (42 versus 53%). The difference in cumulative live birth rate was not significant [hazard ratio = 0.75, 95% CI (0.49, 1.13); P = 0.17].

CONCLUSIONS

Increasing the concentration of sucrose in the freezing medium improves embryo survival, but this is not reflected by increased cumulative birth rates.

Clinical Trials Registration number: ISRCTN93314892.

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