STUDY QUESTION

Can the pronuclei (PN) morphology and the time of PN breakdown (PNB) predict the potential of embryos to result in live birth?

SUMMARY ANSWER

In comparison to embryos resulting in no live birth, PNB occurred significantly later in embryos resulting in live birth and never earlier than 20 h 45min. None of the tested scoring systems were shown to predict the live birth outcome in a time-lapse set-up.

WHAT IS KNOWN ALREADY

The PN morphology is supported as a prominent embryo selection parameter in single light microscopy observations, although controversial results have been reported.

STUDY DESIGN, SIZE, DURATION

This was a prospective study of 159 embryos, all of which were later transferred. The PN morphology of 46 embryos which resulted in live birth was compared with that of 113 embryos which resulted in no live birth.

PARTICIPANTS, SETTING

From 1 March 2010 to 30 August 2011, 130 couples underwent fertility treatment by ICSI. Embryo culture was performed in a time-lapse set-up from fertilization to intrauterine transfer. PN morphological assessment was performed on every embryo replaced, using six different scoring systems at different times.

MAIN RESULTS AND THE ROLE OF CHANCE

No embryo with PNB earlier than 20 h 45 min resulted in live birth. All six PN assessment models showed no significant distribution of scores (P = NS) between the live birth and no live birth groups at 16 h post-fertilization (PF), 18 h PF and 40 min before PNB. The outcomes of assessments changed significantly (P < 0.001) over time and the time of PNB was found to be the optimal stage to evaluate the PN morphology.

LIMITATIONS, REASONS FOR CAUTION

The study includes only embryos reaching the 4-cell stage after ICSI, and transferred at 44 h PF.

WIDER IMPLICATIONS OF THE FINDINGS

The PN morphology changes over time, indicating that the single light microscopy observation approach is deficient in comparison to time-lapse. Although the assessment of the PN morphology does not improve embryo selection, the timing of PNB should be included in embryo selection parameters.

STUDY FUNDING/COMPETING INTEREST(S)

None.

TRIAL REGISTRATION NUMBER

Approval number from the National Ethical Committee of Medical Science of Denmark: SJ-250.

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

STUDY QUESTION

What are the incidence and factors associated with uterine perforation by modern copper intrauterine device (Cu-IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS)?

SUMMARY ANSWER

Perforation incidence was similar to that reported in prior studies and did not vary between Cu-IUD and LNG-IUS groups. Lactation, amenorrhoea and a post-partum period of <6 months were common.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS

The study supports findings in prior studies. The incidence rate was low and factors associated with uterine perforation were similar to those in earlier reports.

DESIGN AND DATA COLLECTION METHOD

This retrospective population-based registry study included 68 patients surgically treated for uterine perforation by an intrauterine device (IUD)/intrauterine system (IUS) at clinics in the Helsinki and Uusimaa hospital district.

PARTICIPANTS AND SETTING

Records of 108 patients with probable uterine perforation by an IUD/IUS were analysed, leaving 68 patients treated for uterine perforation.

RECRUITMENT/SAMPLING STRATEGY

Patients with diagnostic and surgical treatment codes indicating uterine perforation by an IUD/IUS between 1996 and 2009 were retrospectively selected from the Finnish National Hospital Register.

DATA ANALYSIS METHOD

Patients with Cu-IUDs (n = 17) and the LNG-IUS (n = 51) were analysed as one group and also compared using Mann–Whitney and chi-square tests. IUD/IUS sales numbers were used to calculate incidences.

MAIN FINDINGS

The overall incidence of perforation was 0.4/1000 sold devices, varying annually from 0 to 1.2/1000. The proportion of both sold and perforating LNG-IUSs increased during the study period, but perforation incidence was not affected. Demographic characteristics in the Cu-IUD and LNG-IUS groups were similar. More than half of the devices (55%) were inserted at <6 months post-partum. Breastfeeding at the time of insertion was common, comprising 32% of all patients. Moreover, of the breastfeeding women, 90% had delivered within 6 month prior to insertion.

IMPLICATIONS

The population-based study setting represents a good overview of patients experiencing uterine perforation with an IUD/IUS. As previously reported, the post-partum period, lactation and amenorrhoea may increase the risk of perforation.

BIAS, LIMITATIONS AND GENERALIZABILITY

As the study setting revealed only symptomatic patients or those attending regular follow-up, the true incidence might be somewhat higher. As there is no specific diagnostic code for uterine perforation or treatment, it is unlikely that all cases of uterine perforation can be identified in a retrospective study.

STUDY FUNDING/POTENTIAL COMPETING INTERESTS

Helsinki University Central Hospital research funds are acknowledged.

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

BACKGROUND

Unilocular-solid ovarian cysts are a rare but challenging pathology in young women, with a desire to spare their fertility. In these cases, the risks of borderline and invasive disease are around 10 and 20%, respectively. No ultrasound rule has yet demonstrated the ability to discriminate with high accuracy, a borderline tumor from a benign tumor or ‘invasive tumor’. The aim of this study was to assess the predictive performance of different ultrasound parameters in differentiating benign and borderline tumors versus invasive malignant tumors in premenopausal patients with unilocular-solid ovarian masses.

METHODS

Women aged ≤50 years with unilocular-solid adnexal masses with a maximum diameter ≤10 cm, undergoing surgery in our department within 3 months from ultrasound examination, were included in this retrospective study. A standardized ultrasound examination technique and predefined definitions of ultrasound characteristics were used. The results of ultrasound examination using gray scale and color Doppler were compared with the histological examination of the respective surgical specimens.

RESULTS

The study included 51 patients. On histological examination, 36 (70%) lesions were classified as benign, 10 (20%) as borderline ovarian tumors and 5 (10%) as invasively malignant tumors. In receiver-operating characteristic curve analysis, the best cut-off for the largest solid component with regard to discriminating non-invasive (benign or borderline) from invasive tumors was 14 mm. A largest solid component >14 mm, the presence of papillation blood flow and the combination of the two parameters provided a sensitivity of 100% and a specificity of 63, 63 and 80%, respectively.

CONCLUSIONS

Transvaginal ultrasound examination seems to be able to discriminate between invasive and non-invasive tumors in the premenopausal patients with unilocular-solid adnexal masses. Because of the retrospective nature of the study, further prospective clinical trials are needed to confirm the accuracy of the selected sonographic parameters in discriminating the invasive and non-invasive adnexal tumors.

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

STUDY QUESTION

Can uterine scar healing after laparoscopic intracapsular myomectomy (LIM) be adequately monitored by traditional two-dimensional (2D) ultrasound (US) and Doppler velocimetry?

SUMMARY ANSWER

The myometrial area of the scar after LIM can be followed by 2D US and Doppler velocimetry.

WHAT IS KNOWN ALREADY

Apart from post-surgical adhesions, the main concern linked to laparoscopic myomectomy is the quality of healing of the myometrial incision: it has been suggested that US could be useful for assessing uterine scars after myomectomy. However, no diagnostic method has yet been widely accepted to assess the healing process.

STUDY DESIGN, SIZE, DURATION

A cohort prospective study (level of evidence II-2), run in University-affiliated hospitals: 149 women with symptomatic uterine fibroids (UFs) underwent LIM, between January 2007 and October 2011. During follow up 13 patients withdrew from the study.

PARTICIPANTS/MATERIALS, SETTING, METHODS

After LIM, all patients were followed by traditional 2D US scanning and Doppler velocimetry on Days: 0, 1, 7, 30 and 45. Authors evaluated: number, size and location of UFs, scar diameter and Doppler velocimetry and resistance index (RI) of the uterine arteries, at their ascending branch.

MAIN RESULTS AND THE ROLE OF CHANCE

The uterine examination showed a significant (P < 0.05) progressive reduction of uterine scar area from 78% of the previous UF location on the first day, to 19% on 30th day, and <4% on the 45th day. There was no correlation with the size of the fibroid or the relative reduction in the size of the scar, on both Days 1 and 45. There was a significant (P < 0.05) increase in the RI of the ipsilateral uterine arteries from 0.65 on the first post-operative day to 0.83 after 7 days followed by a decrease to 0.71 on the 30th and 0.61 on the 45th post-operative day.

LIMITATIONS, REASONS FOR CAUTION

This is a cohort investigation on a limited number of patients and it does not surgically compare LIM and ‘classic’ myomectomy in the scar US follow up.

WIDER IMPLICATIONS OF THE FINDINGS

LIM avoided intraoperative bleeding and excessive tissue damage, as post-operative US follow up showed, with just two intra-myometrial hematomas (1.5%). The 2D US and Doppler velocimetry, a non-invasive safe method to check the myometrium after LIM, can detect post-operative hematoma and disechogenic, heterogeneous or ill-defined scar area, all unfavorable signs for myometrial scarring. Moreover, Doppler transvaginal monitoring, evaluating the pulsatility index (PI) and RI of the uterine arteries at their ascending branch, could identify patients with altered PI and RI parameters, possible markers of impaired wound healing.

STUDY FUNDING/COMPETING INTEREST(S)

None.

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

STUDY QUESTION

Is there a difference in the characteristics of uterine peristalsis in natural and controlled ovarian hyperstimulation (COH) cycles?

SUMMARY ANSWER

COH significantly changed the uterine peristaltic pattern.

WHAT IS KNOWN ALREADY

In natural menstrual cycles, the periodic changes of uterine peristalsis are closely related to the reproductive process.

STUDY DESIGN, SIZE, DURATION

This is a prospective cohort study with a total of 64 subjects involved. The study was performed between May 2011 and August 2011.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Sixty-four infertile women with regular, ovulatory menstrual cycles underwent follicular tracking in one natural cycle and after ovarian stimulation (GnRH-agonist down-regulation) in the subsequent cycle (COH). Three time points were studied in both cycles: at LH surge/HCG plus 1 day, ovulation/oocyte retrieval and 2 days after ovulation/retrieval. The study was performed in an IVF center of the university-affiliated Xiangya hospital.

MAIN RESULTS AND THE ROLE OF CHANCE

Uterine peristaltic wave frequency was 1.31 times higher in the COH than in the natural cycle (P< 0.01). At all three time points in the COH cycle, waves moving from the cervix to fundus dominated, comprising 80–90% of the wave types observed, while ‘no activity’ was more frequently observed in the natural cycle. The wave frequency was positively correlated with the level of serum estradiol (E₂) (r= 0.30; P< 0.01) and negatively correlated with the progesterone level (r= –0.48; P< 0.01) for the physiological range of steroid levels. No correlation was found between the wave frequency and supraphysiological concentrations of E₂ or progesterone.

LIMITATIONS, REASONS FOR CAUTION

The two observers were not independent and this was a limitation of the study. Quantitative measurements of wave amplitude in the different cycles should be compared in future research.

WIDER IMPLICATIONS OF THE FINDINGS

Uterine peristalsis was much higher in the COH cycle than in the natural cycle. The endometrial movements did not weaken to the natural level before embryo transfer, even with high levels of progesterone. The wave frequency was positively correlated with serum E₂ level and negatively correlated with that of progesterone within the physiological range. No correlation was found between the wave frequency and supraphysiological concentrations of E₂ and progesterone.

STUDY FUNDING/COMPETING INTEREST(S)

The authors declare that they have no study funding or competing interests in this study.

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

BACKGROUND

Although close observation of serum estradiol (E2) levels remains a mainstay of assessing clinical response to controlled ovarian stimulation, the prognostic value of any change in E2 levels after administration of hCG remains unclear. The objective of this study is to evaluate the relationship between serum E2 response after hCG administration and the clinical pregnancy and live birth rates in fresh IVF cycles.

METHODS

We conducted a retrospective cohort study of women aged 21–45 years undergoing their first IVF cycle from 1999 to 2008 at a single practice. We compared the post-hCG serum E2 level with values on the day of hCG trigger. IVF cycles were stratified by post-hCG E2 response and appropriate parametric and non-parametric statistics were performed. Clinical intrauterine pregnancy and live births were the primary outcomes of interest. Multivariable logistic regression models were created to identify predictive factors associated with outcomes while adjusting for potential confounders.

RESULTS

Among the 1712 IVF cycles, 1065 exhibited a >10% increase (Group A), 525 had a plateau (±10%, Group B) and 122 showed a >10% decrease (Group C) in post-hCG E2 levels. While the E2 levels on the day of hCG were similar across groups, Group C had more patients with diminished ovarian reserve, required higher gonadotrophin doses and had the lowest implantation rates. After adjusting for age, total gonadotrophin dose, infertility diagnosis, number of oocytes and number of transferred embryos, the associations between post-hCG E2 decline (Group C) and clinical pregnancy [adjusted odds ratio (aOR): 0.53; 95% confidence interval (CI): 0.33–0.84, P= 0.007] and live birth (aOR: 0.40; 95% CI: 0.22–0.71, P= 0.002) were significant. We also found significant associations between E2 plateau (Group B) and clinical pregnancy (aOR: 0.73; 95% CI: 0.57–0.94, P= 0.013) and live birth (aOR: 0.74; 95% CI: 0.56–0.97, P= 0.032) when adjusting for the same factors.

CONCLUSIONS

In our study, >10% decrease in E2 levels after hCG administration was associated with 40–50% reduction in clinical pregnancy and live birth rates. Similarly, post-hCG E2 plateau (±10%) lowered the clinical pregnancy and live birth rates by >25%. Our study suggests that the change in the post-hCG E2 level is another parameter that can be used by clinicians to counsel patients regarding their likelihood of success with assisted reproductive technologies prior to oocyte retrieval.

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

Background

At present, the only way to conclusively diagnose endometriosis is laparoscopic inspection, preferably with histological confirmation. This contributes to the delay in the diagnosis of endometriosis which is 6–11 years. So far non-invasive diagnostic approaches such as ultrasound (US), MRI or blood tests do not have sufficient diagnostic power. Our aim was to develop and validate a non-invasive diagnostic test with a high sensitivity (80% or more) for symptomatic endometriosis patients, without US evidence of endometriosis, since this is the group most in need of a non-invasive test.

Methods

A total of 28 inflammatory and non-inflammatory plasma biomarkers were measured in 353 EDTA plasma samples collected at surgery from 121 controls without endometriosis at laparoscopy and from 232 women with endometriosis (minimal–mild n = 148; moderate–severe n = 84), including 175 women without preoperative US evidence of endometriosis. Surgery was done during menstrual (n = 83), follicular (n = 135) and luteal (n = 135) phases of the menstrual cycle. For analysis, the data were randomly divided into an independent training (n = 235) and a test (n = 118) data set. Statistical analysis was done using univariate and multivariate (logistic regression and least squares support vector machines (LS-SVM) approaches in training- and test data set separately to validate our findings.

Results

In the training set, two models of four biomarkers (Model 1: annexin V, VEGF, CA-125 and glycodelin; Model 2: annexin V, VEGF, CA-125 and sICAM-1) analysed in plasma, obtained during the menstrual phase, could predict US-negative endometriosis with a high sensitivity (81–90%) and an acceptable specificity (68–81%). The same two models predicted US-negative endometriosis in the independent validation test set with a high sensitivity (82%) and an acceptable specificity (63–75%).

Conclusions

In plasma samples obtained during menstruation, multivariate analysis of four biomarkers (annexin V, VEGF, CA-125 and sICAM-1/or glycodelin) enabled the diagnosis of endometriosis undetectable by US with a sensitivity of 81–90% and a specificity of 63–81% in independent training- and test data set. The next step is to apply these models for preoperative prediction of endometriosis in an independent set of patients with infertility and/or pain without US evidence of endometriosis, scheduled for laparoscopy.

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

STUDY QUESTION

What is the current management of women with ovarian endometriomas undergoing assisted reproductive treatment (ART) in the UK?

SUMMARY ANSWER

It appears that the majority of gynaecologists in the UK offer surgery (mostly cystectomy) for endometriomas prior to ART, regardless of the presence of symptoms.

WHAT IS KNOWN ALREADY

The ideal management of endometriomas in women undergoing ART remains controversial and presents a dilemma to reproductive specialists.

STUDY DESIGN, SIZE AND DURATION

This was a national cross-sectional survey. A total of 388 gynaecologists completed the questionnaire.

PARTICIPANTS, SETTINGS AND METHODS

All clinicians fully registered with the Royal College of Obstetricians and Gynaecologists were contacted. An 11-item survey was administered electronically using Survey Monkey software. Quantitative data were analysed using descriptive and comparative statistics.

MAIN RESULTS AND THE ROLE OF CHANCE

The majority of responders were consultants (65%), 25% practiced ART and 65% performed laparoscopic surgery. Overall, 95% of responders would offer surgery for endometriomas in women undergoing ART, either on the basis of the size (>3–5 cm) of the endometrioma (52%), the presence of symptoms (16%), the presence of multiple/bilateral endometriomas (2%), regardless of the size and symptoms (19%) or only to women undergoing IVF (6%). The remaining 5% of responders would not offer surgery before ART. Excision was the most common surgical modality (68%), followed by ablation (25%). Laparoscopic surgeons were almost twice as likely to ‘offer surgery to all patients with endometriomas prior to ART’ compared with clinicians performing laparotomy (22 versus 12%, P < 0.001).

LIMITATIONS, REASONS FOR CAUTION

Our overall response rate, with answers to the questionnaire, was low (15%). However, the response rate amongst reproductive specialists was estimated at 60%. It is possible that there might have been an element of bias towards over-representation of responders who are more concerned about ‘normalization’ of the pelvic anatomy. Furthermore, our survey relied on self-reporting of practice and it is possible that being presented with a list of ‘ideal’ options may have resulted in respondent bias.

WIDER IMPLICATIONS OF THE FINDINGS

Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients.

STUDY FUNDING/COMPETING INTERESTS

None.

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

BACKGROUND

Life history models suggest that biological preparation for current versus longer term reproduction is favored in environments of adversity. In this context, we present a model of reproductive aging in which environmental adversity is proposed to increase the number of growing follicles at the cost of hastening the depletion of the ovarian reserve over time. We evaluated this model by examining psychological stress in relation to reproductive aging indexed by antral follicle count (AFC), a marker of total ovarian reserve. We hypothesized that stress would be related to (i) higher AFC in younger women, reflecting greater reproductive readiness as well as (ii) greater AFC loss across women, reflecting more accelerated reproductive aging.

METHODS

In a multi-ethnic, community sample of 979 participants [ages 25–45 (mean (standard deviation) = 35.2 (5.5)); 27.5% Caucasian] in the Ovarian Aging study, an investigation of the correlates of reproductive aging, the interaction of age-x-stress was assessed in relation to AFC to determine whether AFC and AFC loss varied across women experiencing differing levels of stress. Stress was assessed by the perceived stress scale and AFC was assessed by summing the total number of antral follicles visible by transvaginal ultrasound.

RESULTS

In linear regression examining AFC as the dependent variable, covariates (race/ethnicity, socio-economic status, menarcheal age, hormone-containing medication for birth control, parity, cigarette smoking, bodymass index, waist-to-hip ratio) and age were entered on step 1, stress on step 2 and the interaction term (age-x-stress) on step 3. On step 3, significant main effects showed that older age was related to lower AFC (b = –0.882, P = 0.000) and greater stress was related to higher AFC (b = 0.545, P = 0.005). Follow-up analyses showed that the main effect of stress on AFC was present in the younger women only. A significant interaction term (b = –0.036, P = 0.031) showed the relationship between age and AFC varied as function of stress. When the sample was divided into tertiles of stress, the average follicle loss was –0.781, –0.842 and –0.994 follicles/year in the low-, mid- and high-stress groups, respectively.

CONCLUSIONS

Psychological stress was related to higher AFC among younger women and greater AFC decline across women, suggesting that greater stress may enhance reproductive readiness in the short term at the cost of accelerating reproductive aging in the long term. Findings are preliminary, however, due to the cross-sectional nature of the current study.

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

STUDY QUESTION

Can the modified polycystic ovary syndrome health-related quality-of-life questionnaire (MPCOSQ) be validated in Iranian patients with polycystic ovary syndrome (PCOS) to provide an instrument for future outcome studies in these patients?

SUMMARY ANSWER

We show initial reliability and validity of the Iranian version of the MPCOSQ as a specific instrument to measure health-related quality of life (QOL) in patients with PCOS in Iran.

WHAT IS KNOWN ALREADY

The prevalence of PCOS in Iran is relatively high and studying QOL in these patients is important. The PCOSQ has previously been translated and validated in Iran but no studies had examined the psychometric properties of the MPCOSQ in Iran.

STUDY DESIGN, SIZE, AND DURATION

This was a cross-sectional study. After linguistic validation of the Iranian version of MPCOSQ, an expert panel evaluated the items by assessing the content validity index (CVI) and content validity ratio (CVR). Then a semi-structured interview was conducted to assess face validity. Consequently, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to indicate the scale constructs (n = 200). In addition, reliability analyses including internal consistency and test–retest analysis were carried out.

PARTICIPANTS/MATERIALS, SETTING, AND METHODS

This study was carried out on women with PCOS (n = 200) who attended two private gynecology clinics in Kashan, Iran. Patients were eligible if they met each of the following criteria: 15–40 years of age; married; not having non-classic adrenal hyperplasia, thyroid dysfunction and hyperprolactinemia; Iranian; not having problems in speaking or listening; having two of the following Rotterdam diagnostic criteria: (i) polycystic ovaries visualized on ultrasound scan (presence of 12 follicles or more in one or both ovaries and/or increased ovarian volume >10 ml), (ii) clinical signs of hyperandrogenism (the hirsutism score based on the Ferriman–Gallwey score >7 or obvious acne) and/or an elevated plasma testosterone (normal range testosterone <2 nmol/l), (iii) having an interval between menstrual periods >35 days and/or amenorrhea as the absence of vaginal bleeding for at least 6 months, i.e. 199 days.

MAIN RESULTS AND THE ROLE OF CHANCE

CVI and CVR scores for MPCOSQ were 0.96 and 0.92, respectively. A six-factor solution (emotional disturbance, weight, infertility, acne, menstrual difficulties and hirsutism) emerged as a result of an EFA and explained 0.64% of the variance observed. The result of the EFA supported the item ‘late menstrual period’ being placed in the menstrual rather than the emotional subscale. The results of the CFA for six-factor model for MPCOSQ indicated an acceptable fit for the proposed model. Additional analyses indicated satisfactory results for internal consistency (Cronbach's alpha ranging from 0.76 to 0.92) and intraclass correlation coefficients (ranging from 0.71 to 0.92). Moving ‘late menstrual period’ from the emotional to the menstrual subscale significantly improved the reliability coefficient for both subscales.

LIMITATIONS, REASONS FOR CAUTION

Study of patients with PCOS attending two private gynecology clinics may limit generalization of the findings to the entire population with PCOS. All patients in this study were married for cultural reasons in Iran. Therefore, the results of the present study have to be interpreted with some caution.

WIDER IMPLICATIONS OF THE FINDINGS

The Iranian version of the MPCOSQ will fill an important gap in measuring the QOL in patients with PCOS in the research and community settings in Iran.

STUDY FUNDING/COMPETING INTEREST(S)

The authors declare that they have no conflict of interest.

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

BACKGROUND

Cell properties, such as attachment, adhesion and invasion, are important for the normal function of the endometrium. However, it is believed that the same properties may also be involved in the development of gynaecological diseases, such as endometriosis. Endometrial cells, shed by retrograde menstruation, may have an aberrant expression of molecules involved in these functions, leading to endometriosis. Therefore, the aim of this study was to investigate the expression of proteins involved in adhesion, attachment and invasion in eutopic and ectopic endometrium.

METHODS

Endometrial biopsy specimens were collected from healthy volunteers (controls: proliferative phase, n = 10; secretory phase, n = 15) and from endometriosis patients (proliferative phase: n = 9, secretory phase: n = 10). Biopsy specimens from endometriomas were also collected (proliferative phase: n = 9, secretory phase: n = 10). Expression of apolipoprotein E (ApoE), integrin β-2 (ITGB2), integrin β-7 (ITGB7), Laminin -1 (LAMC1), CD24 molecule (CD24) and junctional adhesion molecule-1 (JAM-1) was evaluated with real-time reverse transcriptase polymerase chain reaction and immunohistochemistry.

RESULTS

The endometrium from controls and women with endometriosis expressed ApoE, ITGB2, ITGB7, LAMC1, CD24 and JAM-1. Gene expression of ApoE and JAM-1 was decreased in both proliferative and secretory phase in the endometrium from women with endometriosis compared with control endometrium. Also, mRNA expression of LAMC1 was reduced in the endometrium from endometriosis patients compared with controls in the proliferative phase. An altered gene expression of CD24 was seen between the endometrium from endometriosis patients and endometriomas in the secretory phase. The ITGB2 protein expression was altered in epithelia cells between the endometrium from healthy volunteers and endometriosis patients in the secretory phase.

CONCLUSIONS

We have shown differential expression of adhesion, attachment and invasion proteins in proliferative and secretory endometrium from controls and endometriosis patients and in endometriomas. This study suggests that molecules with these properties may have a role in the anchoring of endometrial cells at ectopic sites, thus initiating the development of endometriosis.

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

BACKGROUND

Earlier reviews have suggested that IVF/ICSI pregnancies are associated with higher risks. However, there have been recent advances in the way IVF/ICSI is done, leading to some controversy as to whether IVF/ICSI singletons are associated with higher perinatal risks. The objective of this systematic review was to provide an up-to-date comparison of obstetric and perinatal outcomes of the singletons born after IVF/ICSI and compare them with those of spontaneous conceptions.

METHODS

Extensive searches were done by two authors. The protocol was agreed a priori. PRISMA guidance was followed. The data were extracted in 2 x 2 tables. Risk ratio and risk difference were calculated on pooled data using Rev Man 5.1. Quality assessment of studies was performed using Critical Appraisal Skills programme. Sensitivity analysis was performed when the heterogeneity was high (I² > 50%).

RESULTS

There were 20 matched cohort studies and 10 unmatched cohort studies included in this review. IVF/ICSI singleton pregnancies were associated with a higher risk (95% confidence interval) of ante-partum haemorrhage (2.49, 2.30–2.69), congenital anomalies (1.67, 1.33–2.09), hypertensive disorders of pregnancy (1.49, 1.39–1.59), preterm rupture of membranes (1.16, 1.07–1.26), Caesarean section (1.56, 1.51–1.60), low birthweight (1.65, 1.56–1.75), perinatal mortality (1.87, 1.48–2.37), preterm delivery (1.54, 1.47–1.62), gestational diabetes (1.48, 1.33–1.66), induction of labour (1.18, 1.10–1.28) and small for gestational age (1.39, 1.27–1.53).

CONCLUSIONS

Singletons pregnancies after IVF/ICSI are associated with higher risks of obstetric and perinatal complications when compared with spontaneous conception. Further research is needed to determine which aspect of assisted reproduction technology poses most risk and how this risk can be minimized.

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

BACKGROUND

Threatened miscarriage is very common in early pregnancy. Chinese medicines have been widely used to prevent spontaneous pregnancy loss. However, the safety of Chinese medicines is still unknown. A systematic review was performed to identify and describe adverse events of Chinese medicines used for threatened miscarriage.

METHODS

Clinical studies of Chinese medicines for threatened miscarriage were selected. Primary outcomes were occurrence of adverse effects or toxicity of Chinese medicines. Secondary outcomes were failure of treatment and adverse pregnancy and perinatal outcomes.

RESULTS

Thirty-two relevant articles included 9 randomized controlled trials, 1 quasi-randomized controlled trial and 2 controlled trials comparing Chinese medicines alone or combined medicines with pharmaceuticals and 20 case series with no controls. Sample sizes of each study were generally small. There was variation in Chinese medicine formulation, dosage and duration of treatment. In the pooled randomized controlled trials, dry mouth, constipation and insomnia (2–10%) and intervention failure (3.1–22.3%), diabetic complications (3%), preterm delivery (5%) and neurodevelopmental morbidity (1.8%) were recorded. Meta-analysis demonstrated that intervention failure was significantly lower in the combined Chinese medicines groups than in the Western medicines controls (relative risk = 0.46; 95% confidence interval: 0.30–0.70, I²= 0%). No significant differences were found between these groups for adverse effects and toxicity or for adverse pregnancy and perinatal outcomes.

CONCLUSIONS

Studies varied considerably in design, interventions and outcome measures, therefore conclusive results remain elusive. In the absence of placebo-controlled trials, the safety of Chinese medicines for the treatment of threatened miscarriage is unknown. Rigorous scientific and clinical studies to assess the possible risks of Chinese medicines are needed.

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

BACKGROUND

Chemotherapy treatment in premenopausal women is associated with an increased risk of premature ovarian failure (POF) but the exact mechanism through which this occurs is uncertain. In this review we examine the current evidence for the direct action of chemotherapeutic agents on the ovary and discuss possible molecular pathways through which follicle loss may occur.

METHODS

A systemic search of the databases, PubMed and Google Scholar, was made for all English language articles through to 2011 in each subject area discussed.

RESULTS

POF results from the loss of primordial follicles but this is not necessarily a direct effect of the chemotherapeutic agents. Instead, the disappearance of primordial follicles could be due to an increased rate of growth initiation to replace damaged developing follicles. Likewise, the loss of oocytes need not necessarily be a direct result of damage: evidence suggests that chemotherapy drugs can also induce oocyte death indirectly via damage to somatic cells. Specific molecular mechanisms and likely ovarian targets are discussed for some of the anti-cancer drugs most commonly used to treat premenopausal women. Finally, we consider current and prospective methods of preserving fertility.

CONCLUSIONS

It is likely that different chemotherapeutic drugs act through a range of mechanisms and on different target cells. More research into the cellular mechanisms underpinning chemotherapy-induced follicle loss could lead to the generation of treatments specifically designed to prevent POF.

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

BACKGROUND

Vitrification is now a commonly applied technique for cryopreservation in assisted reproductive technology (ART) replacing, in many cases, conventional slow cooling methodology. This review examines evidence relevant to comparison of the two approaches applied to human oocytes and embryos at different developmental stages.

METHODS

Critical review of the published literature using PubMed with particular emphasis on studies which include data on survival and implantation rates, data from fresh control groups and evaluation of the two approaches in a single setting.

RESULTS

Slow cooling is associated with lower survival rates and compromised development relative to vitrification when applied to metaphase II (MII) oocytes, although the vitrification results have predominantly been obtained using direct contact with liquid nitrogen and there is some evidence that optimal protocols for slow cooling of MII oocytes are yet to be established. There are no prospective randomized controlled trials (RCTs) which support the use of either technique with pronuclear oocytes although vitrification has become the method of choice. Optimal slow cooling, using modifications of traditional methodology, and vitrification can result in high survival rates of early embryos, which implant at the same rate as equivalent fresh counterparts. Many studies report high survival and implantation rates following vitrification of blastocysts. Although slow cooling of blastocysts has been reported to be inferior in some studies, others comparing the two approaches in the same clinical setting have demonstrated comparable results. The variation in the extent of embryo selection applied in studies can lead to apparent differences in clinical efficiency, which may not be significant if expressed on a ‘per oocyte used’ basis.

CONCLUSIONS

Available evidence suggests that vitrification is the current method of choice when cryopreserving MII oocytes. Early cleavage stage embryos can be cryopreserved with equal success using slow cooling and vitrification. Successful blastocyst cryopreservation may be more consistently achieved with vitrification but optimal slow cooling can produce similar results. There are key limitations associated with the available evidence base, including a paucity of RCTs, limited reporting of live birth outcomes and limited reporting of detail which would allow assessment of the impact of differences in female age. While vitrification has a clear role in ART, we support continued research to establish optimal slow cooling methods which may assist in alleviating concerns over safety issues, such as storage, transport and the use of very high cryoprotectant concentrations.

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

BACKGROUND

Chromosome microarray (CMA) testing allows automatic and easy identification of large chromosomal abnormalities detectable by conventional cytogenetics as well as the detection of submicroscopic chromosomal imbalances.

METHODS

A PubMed search was performed in order to review the current use of CMA testing in the field of human reproduction. Articles discussing the use of CMA in the preimplantation setting, ongoing pregnancies, miscarriages and patients with reproductive disorders were considered.

RESULTS

A high rate of concordance between conventional methods of detecting chromosomal abnormalities [e.g. fluorescence in situ hybridization (FISH), karyotyping] and CMA was reported in the prenatal setting with CMA providing more comprehensive and detailed results as it investigates the whole genome at higher resolution. In preimplantation genetic screening, CMA is replacing FISH and the selection of embryos based on CMA has already resulted in live births. For ongoing pregnancies and miscarriages, CMA eliminates tissue culture failures and artifacts and allows a quick turnaround time. The detection of submicroscopic imbalances [or copy number variants (CNVs)] is beneficial when the imbalance has a clear clinical consequence but is challenging for previously undescribed imbalances, particularly for ongoing pregnancies. Recurrent CNVs have been documented in patients with reproductive disorders; however, the application of CMA in this field is still limited.

CONCLUSIONS

CMA enhances reproductive medicine as it facilitates better understanding of the genetic aspects of human development and reproduction and more informed patient management. Further clinical validation of CMA in the prenatal setting, creation of practice guidelines and catalogs of newly discovered submicroscopic imbalances with clinical outcomes are areas that will require attention in the future.

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

BACKGROUND

The integrity of DNA in spermatozoa is considered an additional parameter of semen quality and a potential fertility predictor. Significant progress has been made in recent years towards the development of reliable tests for sperm chromatin integrity and DNA damage assessment. However, most of the techniques available are labor intensive, require expensive instrumentation or utilize enzymes whose activity could be compromised by the highly condensed nature of sperm chromatin. In addition, all the methods currently available involve the destruction of the sperm tested; none is able to select intact spermatozoa that could then be used for fertilization. The aim of the present study was to create a peptide ligand-based stain, capable of binding specific DNA structures, thereby revealing the presence of DNA damage, preferably in living cells.

METHODS

The peptide was bioinformatically modelled on the critical region of the p53 protein associated with DNA binding and fluorescently labeled with a terminal rhodamine B dye. The ability of this 21 amino acid synthetic peptide (DW1) to detect DNA damage in intact and fixed human spermatozoa was assessed in detail. Human sperm samples (n = 20) were treated with reagents that induce single- and/or double-stranded DNA breaks. The effect of these treatments on peptide-labelling was measured and compared with results obtained using established tests for the evaluation of DNA damage, such as comet assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and sperm chromatin dispersion test.

RESULTS

The peptide had a high affinity for single-stranded DNA, and DNA lesions such as double- and single-stranded breaks. The proportion of spermatozoa with intense staining was found to be closely associated with the percentage of cells possessing DNA damage. The analysis of 10 sperm samples using DW1 staining and TUNEL technique showed a significant correlation between the extent of DNA fragmentation for the two methods (r = 0.892, Pearson's correlation, P< 0.05).

CONCLUSIONS

We have produced a novel peptide-based stain capable of detecting DNA damage in individual sperm cells. Evaluation of sperm DNA fragmentation using this peptide may be an inexpensive and easier to use alternative to the tests in current use. Additionally, although DW1 currently requires removal of the membrane using a detergent, further research may allow this approach to be applied to the selection of viable spermatozoa with intact DNA for use in ICSI and/or intra-cytoplasmic morphologically selected sperm injection.

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

BACKGROUND

The functional reproductive alterations seen in women with type 1 diabetes (T1D) have changed as therapy has improved. Historically, patients with T1D and insufficient metabolic control exhibited a high prevalence of amenorrhea, hypogonadism and infertility. This paper reviews the impact of diabetes on the reproductive axis of female T1D patients treated with modern insulin therapy, with special attention to the mechanisms by which diabetes disrupts hypothalamic–pituitary–ovarian function, as documented mainly by animal model studies.

METHODS

A comprehensive MEDLINE search of articles published from 1966 to 2012 was performed. Animal model studies on experimental diabetes and human studies on T1D were examined and cross-referenced with terms that referred to different aspects of the gonadotropic axis, gonadotrophins and gonadal steroids.

RESULTS

Recent studies have shown that women with T1D still display delayed puberty and menarche, menstrual irregularities (especially oligomenorrhoea), mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause. Animal models have helped us to decipher the underlying basis of these conditions and have highlighted the variable contributions of defective leptin, insulin and kisspeptin signalling to the mechanisms of perturbed reproduction in T1D.

CONCLUSIONS

Despite improvements in insulin therapy, T1D patients still suffer many reproductive problems that warrant specific diagnoses and therapeutic management. Similar to other states of metabolic stress, T1D represents a challenge to the correct functioning of the reproductive axis.

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

BACKGROUND

Disruption of ovulation occurs in different types of clinical infertility. The World Health Organization (WHO) has provided a classification of ovulation disorders. This review focuses on WHO group 2 anovulation.

METHODS

Searches were performed in Medline/PubMed and EMBASE. Each subject summary was presented to the European Society of Human Reproduction and Embryology (ESHRE) Workshop Group, where omissions or disagreements were resolved by discussion.

RESULTS

Disorders resulting in ovulatory disturbances are a relatively common cause of infertility. They occur most frequently in the context of WHO group 2 anovulation as reflected, for example, in the polycystic ovary syndrome (PCOS). The aetiology of PCOS remains unclear but evidence exists for a multifactorial origin with a genetic predisposition. Women with PCOS show an increased time to pregnancy but their eventual family size is not necessarily reduced. Also their frequency of miscarriage does not appear increased. Clomiphene citrate is still the first-line treatment in subfertile anovulatory patients with PCOS, with gonadotrophins and laparoscopic ovarian surgery as second-line options. Aromatase inhibitors show promising results.

CONCLUSIONS

Long-term health risks in patients with WHO group 2 anovulation demand their general health be monitored, even after their reproductive needs have been fulfilled. Metabolic and cardiovascular risk prevention in women with PCOS should start as early as possible. It is not easy to analyse the possible role of PCOS, independent of obesity, metabolic syndrome, insulin resistance and diabetes, on long-term health.

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

BACKGROUND

Clusterin, a heterodimeric glycoprotein found at several sites in the human male reproductive tract, could be a marker of morphologically abnormal spermatozoa, while TUNEL positivity indicates DNA fragmentation. Metabolic disorders such as diabetes mellitus and obesity may compromise sperm quality and fertility of men; however, little evidence specifically links hypertension with the impairment of male reproductive function.

METHODS

By flow cytometric, immunofluorescence (TUNEL assay and clusterin immunolabeling) and immunohistochemical (peroxidase-streptavidin method) analyses, we have compared both clusterin- and TUNEL labeling in ejaculated spermatozoa from healthy normotensive donors and hypertensive subjects with the purpose to reveal possible differences between the two conditions.

RESULTS

Data analysis from the normotensive (n = 25) and hypertensive subjects (n = 25) demonstrate a significant correlation between high levels of clusterin immunolabeling and the presence of sperm DNA damage, which is often associated with abnormal morphology. In the normotensive subjects, a low percentage (15.3 ± 4.5) of spermatozoa positive for high levels of clusterin was detected; however, this percentage significantly increased (30.9 ± 13.0) (P < 0.01) in hypertensive subjects. Standard semen evaluations does not reveal any significant differences between the two groups of subjects, except for a reduced forward motility and lower sperm vitality in the hypertensive subjects.

CONCLUSIONS

This pilot study strongly suggests a relationship between hypertension and markers indicative of poor sperm quality. In hypertensive subjects, high levels of clusterin immunolabeling identified a consistent fraction of ejaculated spermatozoa carrying both DNA fragmentation and strong morphological alterations, which was not correlated with age or with sperm cell mortality. The alternative possibility that sperm damage observed is due to adverse effects of anti-hypertensive drugs does not find support in the literature nor in the drug data sheets. The relationship observed between hypertension and human semen represents a novel and possibly relevant information to be considered in the study of male fertility.

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