Investigation of systemic inflammatory response in first trimester pregnancy failure

BACKGROUND

The contribution of local and systemic inflammation to the pathophysiology of sporadic first trimester miscarriages remains unclear. The objective of this study was to investigate the inflammatory response in the circulation of women presenting with first trimester miscarriage.

METHODS

Levels of tumour necrosis factor alpha (TNFα), TNF receptors 1 and 2, interferon gamma (IFN), interleukin (IL)-6 and IL-10 were assayed using cytometric bead arrays in plasma samples from 29 euploid and 21 aneuploid missed miscarriages, 35 normal pregnant controls and 31 non-pregnant women (NPW). Whole blood flow cytometry was carried out with samples from 17 euploid and 16 aneuploid miscarriages, 18 pregnant controls and 13 NPW.

RESULTS

The plasma of women with euploid miscarriage contained significantly higher circulating levels of TNFα (P < 0.005), IFN (P < 0.005), IL-6 (P < 0.005) and IL-10 (P < 0.01) than that of pregnant controls, irrespective of gestational age. Significantly (P < 0.05) higher TNF-R1 levels at 6–9 weeks, and significantly higher TNFα/IL-6 (P < 0.001) and significantly lower TNFα/IL-10 (P < 0.001) and IFN/IL-10 (P < 0.001) ratios at 10–14 weeks, were also found in euploid miscarriage cases compared with pregnant controls. TNFα/IL-10 ratio in plasma was significantly (P < 0.05) lower in miscarriages with an abnormal karyotype than those with normal karyotype. Normal pregnant women had a significantly higher plasma level of IFN (P < 0.01) and IFN/IL-10 ratio (P < 0.005), a significantly (P < 0.005) lower TNF-R1 level, and a significant (P < 0.05) increase in stimulated TNFα in monocytes, compared with NPW.

CONCLUSIONS

Our data confirm that there is an inflammatory reaction in normal pregnancy compared with the non-pregnant state, which may be disrupted during miscarriage.

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

First trimester serum angiogenic/anti-angiogenic status in twin pregnancies: relationship with assisted reproduction technology

BACKGROUND

The risk of pre-eclampsia (PE) increases in twin pregnancies, especially when assisted reproduction technologies (ART) are used. The aim of this study was to assess angiogenic/anti-angiogenic factors in maternal serum in the first trimester of twin pregnancies and establish if the mode of conception influences angiogenic status.

METHODS

This prospective study enrolled women with twin (n = 61) and singleton (n = 50) pregnancies. Dichorionic twin pregnancies were divided into two groups according to their mode of conception. Singleton pregnancies were used as the control group. Soluble fms-like tyrosine kinase (sFlt-1), free placental growth factor (PlGF) and soluble endoglin (sEng) concentrations were measured in the first trimester maternal serum.

RESULTS

In the first trimester, women with twin pregnancies had higher serum concentrations of the anti-angiogenic factor sFlt-1 than that with singleton pregnancies (3924 ± 250 versus 2426 ± 162 pg/ml, respectively; P < 0.001). Maternal serum PlGF concentrations were lower in singleton pregnancies than those in twin pregnancies (37 ± 3.7 versus 59 ± 5.6, respectively; P < 0.001). Serum concentrations of sFlt-1 were higher in twin pregnancies conceived by ART than those in spontaneous twin pregnancies (4313 ± 389 versus 3522 ± 300 pg/ml, respectively; P < 0.05). No differences between groups were observed for sEng.

CONCLUSIONS

In the first trimester, twin pregnancies conceived using ART showed a heightened anti-angiogenic status that could explain the increased risk of PE in these cases.

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

Trophoblast-derived chemokine CXCL12 promotes CXCR4 expression and invasion of human first-trimester decidual stromal cells

BACKGROUND

The aim of this study was to investigate the role of the chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 (CXCL12/CXCR4) axis on the crosstalk between human first-trimester trophoblast cells (TCs) and decidual stromal cells (DSCs), to contribute to a better understanding of the molecular mechanisms on the interaction between the mother and embryo during pregnancy.

METHODS

CXCR4 on human first-trimester DSC membranes was detected by flow cytometry. The effects of exogenous CXCL12 or TC-conditioned medium (TCM) on proliferation and invasion of DSCs were examined by measuring proliferating cell nuclear antigen (PCNA) and an invasion assay, respectively. Finally, a co-culture model was established to investigate the effect of CXCL12 secreted from TCs on motility of DSCs.

RESULTS

The mean (±SEM) percentage of DSCs positive for CXCR4 was 32.32 ± 7.18%. Human recombinant CXCL12 induced an increase in CXCR4 levels on DSCs via binding to CXCR4 (P < 0.01) but had no effect on the PCNA expression of DSCs. Moreover, both exogenous CXCL12 and TCM reinforced the invasive ability of DSCs via CXCR4 ligation. A co-culture model further confirmed that the enhanced invasiveness of DSCs in co-culture with TCs was inhibited by anti-CXCR4 or anti-CXCL12 neutralizing antibody (both P< 0.01).

CONCLUSIONS

Human first-trimester DSCs express membrane CXCR4 and TC-derived CXCL12 promotes CXCR4 expression and invasion of DSCs via ligation with CXCR4. Our data highlight the role of CXCL12/CXCR4 axis on the co-operation between TCs and DSCs during human first-trimester pregnancy.

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

Embryo culture media and neonatal birthweight following IVF

BACKGROUND

Infants conceived from IVF are at increased risk for low birthweight. Animal studies suggest that embryo culture medium influences birthweight but it is unknown whether this association exists in humans. This study examines the relationship between culture medium and birthweight following IVF.

METHODS

We identified all IVF cycles with start dates between 1 January 1999 and 31 December 2008 that used autologous oocytes with resulting embryos cultured in G1.3, Global or G1.5 medium. The population was restricted to singleton deliveries following Day 3, fresh single embryo transfer, or twin deliveries following Day 3, fresh double embryo transfer, at a gestational age of ≥34 weeks. Only the first cycle during the study period was included for each woman. Women were excluded if the number of gestational sacs on ultrasound differed from the number of infants born. Variables were evaluated with the 2-test or analysis of variance. Multiple linear regressions controlled for potential confounders.

RESULTS

Of the 198 women with singleton deliveries, 102 embryos were cultured in G1.3, 53 in Global and 43 in G1.5 medium. Of the 303 twin deliveries, 172 pairs of embryos were cultured in G1.3, 58 in Global and 73 in G1.5 medium. No significant association between culture medium and birthweight was observed, even when controlling for potential confounders.

CONCLUSIONS

This retrospective study demonstrated no significant association between embryo culture medium and birthweight following IVF. Although our careful selection of patients minimized the influence of potential confounders, further research is required to elucidate this issue with larger numbers of patients.

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

Symmetrical division of mouse oocytes during meiotic maturation can lead to the development of twin embryos that amalgamate to form a chimeric hermaphrodite

BACKGROUND

Gentle compression of mouse oocytes during meiosis-1 prevented the usual extrusion of a small polar body and resulted in the symmetrical division of the ooplasm into two cells of similar size within the zona pellucida. The purpose of our study was to determine whether such cells, equivalent to two small oocytes, were capable of embryonic development and would result in birth following transfer to the uterus.

METHODS

IVF of the 2-celled oocytes was performed and the twin intra-zonal embryos were observed. In each case, the two embryos that originated from fertilized cells with two pronuclei were observed to amalgamate and form a single morula and subsequent blastocyst that was transferred to the uterus of a recipient of a different mouse strain. FISH analysis was performed on sectioned paraffin-embedded tissue of the offspring.

RESULTS

In symmetrically divided oocytes each cell contained a metaphase II spindle. Both cells were fertilizable and cleaved to form twin embryos within the same zona pellucida. Most twin embryos amalgamated to form a single compacted morula, which progressed to hatched blastocysts that contained a single inner cell mass. In total, 104 of these blastocysts were transferred to 19 mice, two of which became pregnant, resulting in the birth of three offspring. FISH analysis showed that one newborn contained both XX and XY cells.

CONCLUSIONS

We found that two small oocytes fertilized within the same zona pellucida to form twin embryos that amalgamate to establish a single chimeric embryo. This may be one mechanism that leads to the formation of a chimeric hermaphrodite when an embryo containing XX cells mixes with its intra-zonal twin containing XY cells.

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

Effect of bacterial vaginosis on the pharmacokinetics of misoprostol in early pregnancy

BACKGROUND

Misoprostol has been shown to be an effective agent for cervical ripening and termination of early pregnancy especially when administered vaginally. Our objective was to evaluate whether bacterial vaginosis (BV) affected the pharmacokinetics of vaginally administered misoprostol during early pregnancy.

METHODS

Ten women with BV and 10 healthy women requesting medical abortion up to 9 weeks of pregnancy were administered 200 mg mifepristone followed 24–48 h later by a single dose of 800 µg misoprostol vaginally. Blood samples were taken before (0 h) and 0.5, 1, 2, 3 and 4 h after misoprostol administration. Misoprostol acid was determined in serum samples using liquid chromatography/tandem mass spectrometry.

RESULTS

All women with BV had a vaginal pH > 4.7. The mean bioavailability measured as the area under the curve (AUC) and maximum concentration (Cmax) appeared higher in the control than in the BV group (1458.7 versus 878.1 pg h/ml) and (630.7 versus 342.5 pg/ml), respectively, but did not achieve statistical significance and there was no other significant difference in the pharmacokinetics between the two groups. However, if two women with vaginal pH > 4.7 were excluded from the control group the difference in AUC240 (1359 versus 878.1 pgh/ml) reached statistical significance (P = 0.048).

CONCLUSIONS

BV had an effect on pharmacokinetics of vaginally administered misoprostol in early pregnancy. However, the results should be interpreted with caution due to the small sample size and marked individual variations.

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

Aberrant expression of metastasis-inducing proteins in ectopic and matched eutopic endometrium of women with endometriosis: implications for the pathogenesis of endometriosis

BACKGROUND

Endometriosis is a metastatic disease without obvious tumorigenesis. Expression of S100P, S100A4, osteopontin (OPN) or anterior gradient homologue 2 (AGR2) proteins can induce metastasis but fail to induce tumorigenesis per se. We now explore whether this group of metastasis-inducing proteins (MIPs) are associated with the pathogenesis of endometriosis.

METHODS

Eutopic endometrial biopsies were taken from 73 women (35 fertile women without endometriosis and 38 women with surgically diagnosed endometriosis). Ectopic endometriotic lesions were collected from eight of the women with endometriosis. The expression of MIPs at the cellular level was evaluated by immunohistochemistry and the presence of these proteins in the endometrial tissues was verified by western blotting and their gene expression was confirmed by RT–PCR.

RESULTS

All four MIPs were immunolocated in the endometrium of control women and S100P, AGR2 and OPN showed a cyclical variation. Proliferative phase eutopic endometrium of both groups showed a similar staining pattern for all MIPs, whereas secretory phase endometrium showed a differential expression between controls and cases. The secretory phase endometrial immunostaining of controls showed weak stromal and perivascular AGR2, and decreased stromal and glandular S100P. In contrast, immunostaining for all MIPs was increased in the late secretory endometrial samples of women with endometriosis and intense immunostaining was seen for S100A4 in the stroma (P< 0.05) and for S100P (P< 0.001) and AGR2 (P< 0.0001) in both glands and stroma (P< 0.001). All active peritoneal endometriotic lesions showed strong immunostaining for each of the MIPs studied.

CONCLUSIONS

We propose that these MIPs enhance endometrial cell invasiveness and contribute to the establishment of ectopic endometriotic deposits after retrograde menstruation.

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

Combined transanal and laparoscopic approach for the treatment of deep endometriosis infiltrating the rectum

BACKGROUND

Two surgical approaches are employed in the treatment of deep infiltrating endometriosis of the rectum (DIER): colorectal resection and nodule excision. In 2009, we introduced a new technique for transanal full thickness disc excision of endometriotic nodules infiltrating the low and middle rectum, using the Contour® Transtar stapler (Ethicon Endo-Surgery inc., Cincinnati, OH, USA). The aim of this retrospective study was to describe the technique and to present data on the feasibility of this technique.

METHODS

From April 2009 to October 2010, all patients presenting with DIER and undergoing full thickness excision using the Contour® Transtar stapler were enrolled in the study. Pre-, intra- and post-operative data were collected and reported.

RESULTS

Six nulliparous women were managed using this technique during the study period. The rectal wall discs removed measured from 40 x 45 to 60 x 50 mm. In two cases, microscopic foci were noted on one of the margins but in four cases the limits were clear. Operating time varied from 180 to 450 min. Four women were completely free of post-operative digestive complaints.

CONCLUSIONS

Despite the small numbers in this series, our data suggest that the new technique of transanal rectal disc excision using the contour stapler may be applied in patients with infiltrating endometrial nodules of the rectum up to 10 cm from the anal margin and up to 5 cm in diameter. This new procedure promises to be a useful addition to the surgeon's armamentarium in a multidisciplinary approach to deep pelvic endometriosis.

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

Identification and validation of novel serum markers for early diagnosis of endometriosis

BACKGROUND

Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis.

METHODS

A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation.

RESULTS

The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis.

CONCLUSIONS

Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.

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

Laparoscopic myomectomy focusing on the myoma pseudocapsule: technical and outcome reports

BACKGROUND

Our aim was to assess surgical complaints and reproductive outcomes of laparoscopic intracapsular myomectomies by a prospective observational study run in University affiliated hospitals.

METHODS

Between 2005 and 2010, 235 women underwent subserous and intramural laparoscopic myomectomy of fibroids (4–10 cm in diameter) for indications of pelvic pain, menstrual disorders, a large growing myoma or infertility. The main outcome measures were post-surgical parameters, including complications, the need for subsequent surgery or symptomatic relief, resumption of normal life and reproductive outcome.

RESULTS

Pelvic pain occurred in 27%, menorrhagia or metorrhagia in 21%, a large growing myoma in 10% and infertility in 42% of women. Single fibroids occurred in 51.9% of patients while 48.1% had multiple myomas. Of all patients, 58.2% had subserosal and 41.8% had intramural myomas. No laparoscopies were converted to laparotomy. In 3 years, 1.2% of patients had a second laparoscopic myomectomy for recurrent fibroids. The mean total operative laparoscopic time was 84 min (range 25–126 min), with mean blood loss of 118 ± 27.9 ml. By 48 h after surgery, 86.3% were discharged with no major post-operative complications. No late complications, such as bleeding, urinary tract infections or bowel lesions, occurred. Of the women who underwent myomectomy for infertility, 74% finally conceived. At term, 32.9% of patients underwent Caesarean section, 24.8% delivered by vacuum extractor and 42.2% had spontaneous deliveries. No case of uterine rupture occurred.

CONCLUSIONS

Intracapsular subserous and intramural myomectomy saving the fibroid pseudocapsule showed few early and no late surgical complications, enhanced healing by preserving myometrial integrity and allowed a good fertility rate and delivery outcome. In young patients suffering fibroids, laparoscopic intracapsular myomectomy is a potential recommended surgical treatment.

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

The non-independence of treatment outcomes from repeat IVF cycles: estimates and consequences

BACKGROUND

It is generally acknowledged that the outcomes of IVF treatments are correlated between repeat cycles in the same couple and that these effects need to be allowed for in the analysis of such treatments. However, there are few studies that have attempted to estimate the magnitude of these effects or their clinical consequences.

METHODS

We use the embryo-uterus model, extended to include inter-cycle correlations in both the embryo and uterine components to estimate these effects in a large data set of 12 480 embryo transfer cycles from 8768 UK IVF patients, including embryo grading parameters. Empirical Bayes estimates are used to predict the consequences of previous cycle failures on the prognosis of future cycles.

RESULTS

Statistically and clinically significant correlations can be detected which amount to a median odds ratio of 2.3 (95% CI: 1.8–2.9) in the chances of an embryo being viable between any two randomly selected patients. These act predominantly through the embryo component of the model. Inclusion of these effects in the embryo model does alter the estimates and predictions, but not dramatically. Around 10 cycle failures are required to reduce the probability of success in future cycles to half that of the initial cycle.

CONCLUSIONS

There are important inter-cycle correlations between embryos transferred across different cycles from the same patients, implying substantial unmeasured prognostic embryo characteristics. The implications for extended culture and cryopreserved embryos need further investigation as well as similar consideration of the other components of treatment, particularly response to stimulation. Although these effects should not be ignored they have limited impact in the development of predictive models for individual cycles, but do need to be accounted for when considering multiple cycle treatment programmes. For individual patients the failure of one or several embryo transfers does not have a big impact on the chances of success in future cycles. The magnitude of the correlations suggests that for any individual couple, previous cycle implantation failures do not imply a greatly reduced prognosis for future cycles.

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

Long-term outcome in couples with unexplained subfertility and an intermediate prognosis initially randomized between expectant management and immediate treatment

BACKGROUND

We recently reported that treatment with intrauterine insemination and controlled ovarian stimulation (IUI-COS) did not increase ongoing pregnancy rates compared with expectant management (EM) in couples with unexplained subfertility and intermediate prognosis of natural conception. Long-term cost-effectiveness of a policy of initial EM is unknown. We investigated whether the recommendation not to treat during the first 6 months is valid, regarding the long-term effectiveness and cumulative costs.

METHODS

Couples with unexplained subfertility and intermediate prognosis of natural conception (n=253, at 26 public clinics, the Netherlands) were randomly allocated to 6 months EM or immediate start with IUI-COS. The couples were then treated according to local protocol, usually IUI-COS followed by IVF. We followed couples until 3 years after randomization and registered pregnancies and resources used. Primary outcome was time to ongoing pregnancy. Secondary outcome was treatment costs. Analysis was by intention-to-treat. Economic evaluation was performed from the perspective of the health care institution.

RESULTS

Time to ongoing pregnancy did not differ between groups (log-rank test P=0.98). Cumulative ongoing pregnancy rates were 72–73% for EM and IUI-COS groups, respectively [relative risk 0.99 (95% confidence interval (CI) 0.85–1.1)]. Estimated mean costs per couple were 3424 (95% CI 880–5968) in the EM group and 6040 (95% CI 4055–8125) in the IUI-COS group resulting in an estimated saving of 2616 per couple (95% CI 385–4847) in favour of EM.

CONCLUSIONS

In couples with unexplained subfertility and an intermediate prognosis of natural conception, initial EM for 6 months results in a considerable cost-saving with no delay in achieving pregnancy or jeopardizing the chance of pregnancy. Further comparisons between aggressive and milder forms of ovarian stimulation should be performed.

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

Nomogram to predict pregnancy rate after ICSI-IVF cycle in patients with endometriosis

BACKGROUND

Although several scoring systems have been published to evaluate the pregnancy rate after ICSI–IVF in infertile patients, none of them are applicable for patients with deep infiltrating endometriosis (DIE) nor can they evaluate the chances of pregnancy for individual patients. The aim of this study was to develop a nomogram based on an association of patients' characteristics to predict the clinical pregnancy rate in patients with endometriosis.

METHODS

This prospective longitudinal study was conducted from January 2007 to June 2010. The nomogram was built from a training cohort of 94 consecutive patients (141 ICSI–IVF cycles) and tested on an independent validation cohort of 48 patients (83 ICSI–IVF cycles). DIE was confirmed in all participants.

RESULTS

The pregnancy rate (per patient) in women with and without DIE was 58 and 83%, respectively (P = 0.03). Increased patient age (P = 0.04), serum anti-Mullerian hormone (AMH) level ≤1 ng/ml (P = 0.03) and increased number of ICSI–IVF cycles (P = 0.03) were associated with a decreased clinical pregnancy rate. The presence of DIE was the strongest determinant factor of the clinical pregnancy rate in our model [odds ratio = 0.26, 95% confidence interval (CI): 0.07–0.9 (P = 0.006)], which also included patient age, serum AMH level and number of attempts at ICSI–IVF. The nomogram showed an area under the curve (AUC) of 0.76 for the training cohort (95% CI: 0.7–0.8) and was well calibrated. The AUC for the validation cohort was 0.68 (95% CI: 0.6–0.75) and calibration was good.

CONCLUSIONS

Our nomogram provides realistic and precise information about ICSI–IVF success and can be used to guide couples and practitioners.

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

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study

BACKGROUND

Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment.

METHODS

Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50–150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR.

RESULTS

Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95% confidence interval (CI) 5.3–25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5–25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4–24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI.

CONCLUSIONS

Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.

Clinical trials registration

ISRCTN41865643.

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

Complications and outcome of assisted reproduction technologies in overweight and obese women

BACKGROUND

Based on a presumed negative impact of overweight and obesity on reproductive capacity and pregnancy outcome, some national guidelines and clinicians have argued that there should be an upper limit for a woman's BMI to access assisted reproductive technologies (ART). However, evidence on the risk of complications or expected success rate of ART in obese women is scarce. We therefore performed a systematic review on the subject.

METHODS

We searched the literature for studies reporting on complications or success rates in overweight and obese women undergoing ART. Articles were scored on methodological quality. We calculated pooled odds ratios (ORs) to express the association between overweight and obesity on the one hand, and complications and success rates of ART on the other hand. We only pooled results if data were available per woman instead of per cycle or embryo transfer.

RESULTS

We detected 14 studies that reported on the association between overweight and complications during or after ART, of which 6 reported on ovarian hyperstimulation syndrome (OHSS), 7 on multiple pregnancies and 6 on ectopic pregnancies. None of the individual studies found a positive association between overweight and ART complications. The pooled ORs for overweight versus normal weight for OHSS, multiple pregnancy and ectopic pregnancy were 1.0 [95% confidence interval (CI) 0.77–1.3], 0.97 (95% CI 0.91–1.04) and 0.96 (95% CI 0.54–1.7), respectively. In 27 studies that reported on BMI and the success of ART, the pooled ORs for overweight versus normal weight on live birth, ongoing and clinical pregnancy following ART were OR 0.90 (95% CI 0.82–1.0), 1.01 (95% CI 0.75–1.4) and OR 0.94 (95% CI 0.69–1.3), respectively.

CONCLUSIONS

Data on complications following ART are scarce and therefore a registration system should be implemented in order to gain more insight into this subject. In the available literature, there is no evidence of overweight or obesity increasing the risk of complications following ART. Furthermore, they only marginally reduce the success rates. Based on the currently available data, overweight and obesity in itself should not be a reason to withhold ART.

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

Should Cochrane reviews be performed during the development of new concepts?

Cochrane reviews are internationally recognized as the highest standard in evidence-based health care. A Cochrane analysis conducts systematic reviews of primary research in human health care, and the analysis includes a comprehensive search of all potentially relevant studies and the use of explicit, reproducible criteria in the selection of studies for review. Thus, Cochrane reviews, undoubtedly provide many useful clinical guidelines. In this opinion paper, however, it is questioned at what level of clinical development of a new strategy a Cochrane review should be conducted in order not to draw premature conclusions that may not be sustained later on. Previous examples of this are debated together with the most recent Cochrane review regarding GnRH agonist triggering of final oocyte maturation, in which debatable conclusions are drawn from early studies, when the concept was still under development. We question the current policy of meta-analysis and recommend that in the future, the meta-analysts should await the results of a sufficient number of well-performed studies with an established new regime before an analysis is performed in order to avoid too early and possibly biased conclusions.

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

The prevalence of chromosomal abnormalities in subgroups of infertile men

BACKGROUND

The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of chromosomal abnormalities, possibly by using parameters other than sperm concentration. The aim of this study was to evaluate several clinical parameters in azoospermic and non-azoospermic men, in order to assess the prevalence of chromosomal abnormalities in different subgroups of infertile men.

METHODS

In a retrospective cohort of 1223 azoospermic men and men eligible for ICSI treatment, we studied sperm parameters, hormone levels and medical history for an association with chromosomal abnormalities.

RESULTS

The prevalence of chromosomal abnormalities in the cohort was 3.1%. No association was found between chromosomal abnormalities and sperm volume, concentration, progressive motility or total motile sperm count. Azoospermia was significantly associated with the presence of a chromosomal abnormality [15.2%, odds ratio (OR) 7.70, P < 0.001]. High gonadotrophin levels were also associated with an increased prevalence of chromosomal abnormalities (OR 2.96, P = 0.013). Azoospermic men with a positive andrologic history had a lower prevalence of chromosomal abnormalities than azoospermic men with an uneventful history (OR 0.28, P = 0.047). In non-azoospermic men, we found that none of the studied variables were associated with the prevalence of chromosomal abnormalities.

CONCLUSIONS

We show that the highest prevalence of chromosomal abnormalities is found in hypergonadotrophic azoospermic men with an uneventful andrologic history.

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

CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis

BACKGROUND

Numerous studies have reported CFTR mutations in CBAVD (congenital bilateral absence of the vas deferens) patients, but their results are not completely consistent. Here, we present a systemic review and meta-analysis with emphasis on clarifying further the genetic association of CFTR mutations with CBAVD.

METHODS

We searched the MEDLINE database until March, 2011 for eligible articles reporting CFTR mutations in CBAVD. Relevant data from each included study were abstracted by two independent reviewers. The overall frequency of CFTR mutations in CBAVD and the odds ratio (OR) for common specific alleles were pooled under random-effect or fixed-effect model as appropriate. Subgroup analysis was performed by ethnicity, and potential heterogeneity and bias were both assessed.

RESULTS

Among CBAVD patients, 78% had at least one CFTR mutation, 46% having two and 28% only one. Moreover, the common heterozygous F508del/5T and F508del/R117H were observed in 17 and 4% of CBAVD cases respectively, and the allele frequency in CBAVD was 17% for F508del, 25% for 5T and 3% for R117H. Subgroup analysis indicated an increased frequency of cases with two mutations in Caucasian patients than in Non-Caucasian (68 versus 50%, P= 0.012), but no differences for cases with at least one mutation (88 versus 77%, P= 0.163) or with only one mutation (17 versus 25%, P= 0.115). Caucasian patients had higher F508del frequency, but lower 5T frequency, than Non-Caucasian (22 versus 8%, P= 0.001; 20 versus 31%, P= 0.009). Summary OR was 9.25 for 5T [95% confidence interval (CI) 7.07–12.11, P= 0.000], with moderate heterogeneity (I2= 49.20%, P= 0.019) and evident bias (Egger's test, P= 0.005), and it was 19.43 for 5T/(TG)12_13 (95% CI 10.48–30.03, P= 0.000) without any evidence of heterogeneity (I2= 0.1%, P= 0.391) and bias (Egger's test, P= 0.160). The OR for 5T/(TG)12_13 was significantly higher than that for 5T allele (P= 0.000).

CONCLUSIONS

In summary, our results demonstrate a high frequency of CFTR mutations in CBAVD patients, and these exhibit evident ethnic differences. In addition, 5T allele and 5T/(TG)12_13 may contribute to the increased risk for CBAVD, with the 5T penetrance probably being modulated by adjacent (TG)12_13.

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