BACKGROUND

Intracytoplasmic sperm injection (ICSI) is the primary treatment for male infertility. However for this procedure, with the exception of visual morphological selection, there is no standardization for sperm selection. Recently, the hypo-osmotic swelling test (HOST) has been proposed to potentially select sperm with intact membranes. The aim of this study is to evaluate the ability of this technique to select functional sperm in terms of apoptosis and morphology, as well as nuclear integrity.

METHODS

A total of 20 semen samples were randomly collected from men who attended the Andrology Unit of the Isfahan Fertility and Infertility Center. Semen samples were washed and exposed to hypotonic conditions, before being fixed and simultaneously assessed for membrane integrity as well as abnormal morphology, DNA fragmentation and protamine deficiency by using Papanicolaou, TUNEL and CMA3 staining techniques, respectively. The remaining semen samples were washed with calcium buffer and stained by Annexin V, then exposed to hypotonic conditions before being assessed for early apoptosis along with membrane integrity.

RESULTS

HOST grade ‘d’, followed by grade ‘c’, showed the highest percentages of healthy sperm, whereas sperm of HOST grade ‘g’ in which anomalies in terms of apoptosis, abnormal head morphology or nuclear immaturity or membrane damage, were most frequently observed in the samples assessed.

CONCLUSIONS

Integration of HOST into the sperm selection procedure may provide a valuable tool for selection of functional sperm required for ICSI. According to this study, insemination of HOST grade ‘g’ sperm should be avoided during ICSI.

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

BACKGROUND

Gap junctions (GJs) allow for direct communication between adjacent cells. They are composed of connexons consisting of transmembrane proteins, connexins (Cxs). The objectives of this study were to determine if GJ proteins GJA1 (Cx43), GJB1 (Cx32) and GJB2 (Cx26) are present in the epididymis of men with a normal epididymis, to assess whether or not Cx expression and localization are altered in azoospermic patients, and to determine if epidermal growth factor (EGF) regulates GJA1 expression.

METHODS

Epididymides were obtained from men with localized testis cancer with active spermatogenesis and histologically normal epididymal tubule (group 1), men with non-obstructive azoospermia secondary to Sertoli-cell only syndrome (group 2) and from azoospermic men with normal spermatogenesis and epididymal obstruction (group 3). Epididymides were subdivided into three segments: caput, corpus and cauda. Quantitative real-time RT–PCR was performed to assess GJA1, GJB1, GJB2 and EGF receptor (EGFR) mRNA levels in epididymides from patients from each group (all n= 3, except n= 1 for caput blockage). A human caput epididymal cell line was then used to determine the role of EGFR signaling on the regulation of human epididymal GJA1.

RESULTS

Real-time RT–PCR analysis revealed that GJA1, GJB1, GJB2 and EGFR were expressed along the human epididymis. In the cauda epididymidis of group 2 and 3 men, we observed a significant decrease in GJA1 (P= 0.0456 and P= 0.0465, respectively) and GJB1 (P= 0.0450 and P= 0.0497, respectively) mRNA levels when compared with group 1 men. We also observed a decrease in EGFR mRNA levels (P= 0.0358) in the cauda epididymidis of group 3 men when compared with group 1. Immunocytochemistry revealed that in the epididymis, GJA1 and EGFR were localized between basal and principal cells and between adjacent principal cells. In group 2 and 3 patients, however, we noted a dramatic increase in cytosolic immunostaining for both GJA1 and EGFR in both principal and basal cells. Using a human caput epididymal cell line derived from fertile men, we demonstrated that changes in GJA1 phosphorylation could be regulated by EGF (P= 0.015) and the extracellular regulated kinase 1/2 signaling pathway (P= 0.03). Furthermore, while the phosphoinositide-3-kinase (PI3K)/AKT signaling pathway did not alter GJA1 phosphorylation, treatment with PI3K/AKT inhibitor LY294002 significantly (P= 0.024) inhibited the EGF-stimulated increase in GJA1 total protein levels at 24 h. Immunolocalization indicated that loss of PI3K/AKT signaling was associated with increased cytosolic localization of Cx43 in this cell line.

CONCLUSIONS

Together, these data suggest that in azoospermic men decreased expression of EGFR may be responsible for decreasing GJA1 levels and increasing its cytosolic localization via the PI3K/AKT signaling pathway.

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

BACKGROUND

We previously found that a normal karyotype in a previous miscarriage is a predictor of subsequent miscarriage. However, the prevalence of recurrent miscarriage caused by an abnormal embryonic karyotype has not yet been reported, since embryonic karyotype is not typically analyzed during conventional examinations.

METHODS

A total of 482 patients who underwent both embryonic karyotype determination and conventional examinations for recurrent miscarriage were enrolled in this study. The distribution of the causes and the live birth rate for each cause were examined.

RESULTS

The total percentage of subjects in whom conventional causes of recurrent miscarriage could be detected was 29.5%. The prevalence of the abnormal embryonic karyotype was 41.1% in the subjects in whom no conventional causes of miscarriage could be identified. The prevalence of recurrent miscarriage of truly unexplained cause, that is, of subjects without conventional causes in whom the embryonic karyotype was ascertained to be normal, was 24.5%. Among the patients in whom the first determination revealed an abnormal embryonic karyotype, 76.2% (32/42) showed an abnormal embryonic karyotype in the repeat determination as well. The cumulative live birth rate (71.9%) in women with recurrent miscarriages caused by the abnormal embryonic karyotype was significantly higher than that (44.7%) in women with recurrent miscarriages associated with the embryonal euploidy.

CONCLUSION

An abnormal embryonic karyotype was found to represent the commonest cause of recurrent miscarriage, and the percentage of cases with recurrent miscarriage of truly unexplained cause was limited to 24.5%.The two groups should be distinguished for both clinical and research purposes.

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

STUDY QUESTION

Is the selection of a single Day 3 embryo by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology able to improve live birth rates in IVF, compared with embryo selection by morphology alone?

SUMMARY ANSWER

The live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryos were selected by morphology alone.

WHAT IS KNOWN ALREADY

The elevated incidence of pregnancy and neonatal problems associated with a high-twinning rate after IVF can only be successfully reduced by the transfer of one embryo. Current embryo assessment methods are unable to accurately predict the reproductive potential of an individual embryo. Today, a number of techniques are said to be more accurate at selecting the best embryo. One of these new technologies is metabolomic profiling of spent embryo culture media with the use of NIR spectroscopy.

STUDY DESIGN, SIZE AND DURATION

A double-blind, randomized controlled trial was conducted between 2009 and 2011, and included 417 couples undergoing IVF with a single embryo transfer. Randomization was performed centrally just before Ovum Pick-Up (OPU), using a computerized randomization program. Both patient and physician were unaware of the treatment allocation. To ensure blinding, the allocations were placed in consecutively numbered, opaque envelopes. Patients were randomized (1:1) into either the control group (embryo selection by morphology only) or the treatment group (embryo selection by morphology plus NIR spectroscopy of embryo culture medium).

PARTICIPANTS/MATERIALS, SETTING AND METHODS

At OPU, 208 patients were randomized to the morphology only group and 209 patients were randomized to the morphology plus viability score group. On Day 3, 163 patients in the control group and 146 patients in the treatment group met the inclusion criteria. The study was conducted in an academic hospital with IVF laboratory and three non-academic hospitals.

MAIN RESULTS AND THE ROLE OF CHANCE

Patient demographics and baseline characteristics were distributed equally over the two groups, except for embryo fragmentation, which was significantly higher in the treatment group. In the intention to treat analysis, the live birth rates were 31.7 and 26.8% for the control group and the treatment group, respectively (relative risk 0.84; 95% confidence interval 0.63–1.14, P = 0.27). In the per protocol analysis, the live birth rates were 31.3 and 29.5% for the control group and the treatment group, respectively (relative risk 0.94; 95% confidence interval 0.67–1.32, P = 0.73). For the treatment group, the embryological technician's independent choice (by morphology) of which embryo to transfer was recorded 138 times. In 75.4% (104 of 138) of the transfers, the embryo with the best morphology did not have the highest viability score. The live birth rate of these 104 transferred embryos was 30.8%.

LIMITATIONS, REASONS FOR CAUTION

A possible limitation of our study is the pre-selection of all embryos by morphology and dividing the cohort of available embryos into two groups: good quality embryos and poor quality embryos. As a consequence, we have probably selected for a better prognosis patient group.

WIDER IMPLICATIONS OF THE FINDINGS

To avoid the use of incompetent embryo selection tools at the expense of the patient, an evidence-based proof of clinical usefulness is essential before the implementation of new diagnostic tools in IVF laboratories.

TRIAL REGISTRATION NUMBERS

Dutch Trial Registry, registry number NTR1178.

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

BACKGROUND

Several studies have demonstrated the derivation of multi- or pluripotent stem cells from testicular cells of both newborn and adult mice by a spontaneous conversion process, when these cells are cultured in vitro for an extended time. To obtain a better and robust derivation, we have attempted to identify small molecules (SMs) that induce reprogramming of testicular cells in culture into germline-derived pluripotent stem cells (gPSCs).

METHODS

We tested several SMs based on previous reports that have shown enhancement of establishment of induced pluripotent stem cells or embryonic stem cells (ESCs) on mouse NMRI (outbred strain) and C57BL/6 (inbred strain) testicular cells. After appearance of ESC-like colonies at Day 6, they were passaged on mitotically arrested mouse embryonic fibroblasts in mouse ESC medium in the absence or presence of SMs up to Day 14. The generated cells were characterized using a variety of experimental approaches.

RESULTS

The application of several SMs involved in pluripotent reprogramming led to the discovery that CHIR99021 (CHIR), a glycogen synthase kinase-3 (GSK-3) inhibitor, promotes efficient derivation of gPSCs from neonatal mouse NMRI and C57BL/6 testes. The pluripotency of the generated cell lines has been confirmed by in vitro spontaneous and direct differentiation toward cardiac and neural lineages, and formation of chimeras after injection of gPSCs into blastocysts. We have shown that the generated gPSCs could be maintained and expanded under chemically defined serum and feeder-free conditions by inhibition of both the extracellular signal-regulated kinases (Erk1/2) and GSK-3.

CONCLUSIONS

To our knowledge, this is the first report of a simple and efficient protocol to reprogram gPSCs from testicular cells solely by inhibition of GSK-3 in two strains of mice with different genetic backgrounds. Additionally, this brings us closer to eliminating the need for genetic modification in pluripotent reprogramming. Future studies will determine whether the inhibition of GSK-3 could affect the generation of naïve gPSCs lines in other mammals.

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

BACKGROUND

Endometriosis is a common cause of pelvic pain and infertility in women of reproductive age. It is characterized by the presence of endometrial tissue outside the normal location, predominantly in the pelvic peritoneum causing severe abdominal pain. However, the severity of the symptoms of endometriosis does not always correlate with the anatomic severity of the disease. This lack of correlation may be due to morphological lesion variation during disease progression. This study examined lesion kinetics in a non-human primate model of endometriosis to better understand lesion dynamics.

METHODS

Endometriosis was experimentally induced in nine normal cycling female adult olive baboons (Papio anubis) by i.p. inoculation of autologous menstrual endometrium on Day 2 of menses for two consecutive menstrual cycles. Diagnostic laparoscopies were performed between Day 8–12 post-ovulation at 1, 3, 6, 9 and 12 months, followed by a necropsy at 15 months, after the second inoculation. In two animals, lesions were excised/ablated at 6 months and they were monitored for lesion recurrence and morphological changes by serial laparoscopy. Furthermore, five control animals underwent surgeries conducted at the same time points but without inoculation.

RESULTS

A total of 542 endometriotic lesions were observed. The location, macroscopic (different colours) and microscopic appearance confirmed distinct endometriosis pathology in line with human disease. The majority of the lesions found 1 month after tissue inoculation were red lesions, which frequently changed colour during the disease progression. In contrast, blue lesions remained consistently blue while white lesions were evident at the later stages of the disease process and often regressed. There were significantly lower numbers of powder burn, blister and multicoloured lesions observed per animal in comparison to black and blue lesions (P-value ≤ 0.05). New lesions were continually arising and persisted up to 15 months post-inoculation. Lesions reoccurred as early as 3 months after removal and 69% of lesions excised/ablated had reoccurred 9 months later. Interestingly, endometriotic lesions were also found in the non-inoculated animals, starting at the 6-month time point following multiple surgeries.

CONCLUSIONS

Documentation of lesion turnover in baboons indicated that lesions changed their colour from red to white over time. Different lesion types underwent metamorphosis at different rates. A classification of lesions based on morphological appearance may help disease prognosis and examination of the effect of the lesion on disease symptoms, and provide new opportunities for targeted therapies in order to prevent or treat endometriosis. Surgical removal of endometriotic lesions resulted in a high incidence of recurrence. Spontaneous endometriosis developed in control baboons in the absence of inoculation suggesting that repetitive surgical procedures alone can induce the spontaneous evolution of the chronic disease. Although lesion excision/ablation may have short-term benefits (e.g. prior to an IVF cycle in subfertile women), for long-term relief of symptoms perhaps medical therapy is more effective than surgical therapy.

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

STUDY QUESTION

What characteristics are associated with a Day 5 embryo transfer?

SUMMARY ANSWER

The use of the Day 5 embryo transfer has increased over time, with clinicians allowing women with typically ‘poorer’ prognostic characteristics to undergo a Day 5 embryo transfer. The mean number of embryos per Day 5 transfer decreased from 2001 to 2009, although the prevalence of the Day 5 single embryo transfer remains low and the rate of multiple births remains substantial.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS

Day 5 embryo transfer may reduce the rate of multiple gestation pregnancy. US trends over time in the prevalence of the Day 5 transfer, changes in characteristics of patients receiving Day 5 transfer, and number of embryos transferred are unknown.

DESIGN

We used 2001–2009 US National assisted reproductive technology (ART) Surveillance System (NASS) data on 620 295 fresh IVF cycles derived from autologous oocytes with a Day 3 or 5 embryo transfer. Trends in the mean number of embryos transferred from 2001 to 2009 were assessed by the day of transfer. For 349 947 cycles from clinics performing both Days 3 and 5 embryo transfers, multivariable logistic regression was used to determine the characteristics associated with the Day 5 embryo transfer. We also compared the characteristics of the Day 5 embryo cycles in 2001 and 2009.

MAIN RESULTS AND THE ROLE OF CHANCE

Overall, the proportion of ART cycles using the Day 5 embryo transfer increased from 12% in 2001 to 36% in 2009 (P< 0.0001), while the mean number of embryos transferred decreased from 2.4 to 2.1 (P< 0.0001). Among Day 5 transfers, the rate of the single embryo transfer tripled from 4.5% in 2001 to 14.8% in 2009 (P< 0.0001); and the rate of multiple births decreased from 44.8 to 41.1% (P< 0.0001). In cycles initiated after 2001, maternal age <35 years, no prior ART cycles, ≥1 prior pregnancies, baseline follicle stimulating hormone <10 international units and ≥10 oocytes retrieved were associated with the Day 5 embryo transfer. Compared with 2001, in 2009, a broader range of candidates received the Day 5 transfer.

BIAS

Women undergoing multiple ART cycles over time are not linked.

CONFOUNDING FACTORS AND OTHER REASONS FOR CAUTION

We ran multivariable logistic regression to lessen the effects of the confounding factors. Cycle cancelation rates by the day of embryo transfer are unknown.

GENERALIZABILITY TO OTHER POPULATIONS

Generalizable to ART clinics included in NASS.

STUDY FUNDING/COMPETING INTERESTS

This study was funded by the Centres for Disease Control. The authors have no competing interests to declare.

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

BACKGROUND

For women with congenital uterine infertility, or for those who have undergone hysterectomy, uterine transplantation is one of the potential treatments to regain fertility. In this study, we utilized a primate model of uterine transplantation, and evaluated the patency of our microsurgical anastomoses, and the perfusion of the transplanted uterus.

METHODS

Two female cynomolgus monkeys underwent surgery. We anastomosed two arteries and one vein in Case 1 and two arteries and two veins in Case 2. The arteries used were the uterine arteries and the anastomosis was done to the external iliac artery. We used one of the ovarian veins in both animals, but resected the ovary from the Fallopian tube. Uterine arterial blood flow and uterine size were determined by intraoperative indocyanine green (ICG) angiography and ultrasonography. The biopsy of the uterine cervix was performed after surgery.

RESULTS

ICG angiography showed that the unilateral uterine artery perfused the bilateral uterine bodies and cervix. In Case 1, ICG angiography showed the occlusion of one of the anastomosed arteries during the operation and the uterus appeared atrophied 2 months after operation. In Case 2, the transplanted uterus survived and normal menstruation occurred. The animal achieved a natural pregnancy and was delivered by the Caeserean section due to early separation of the placenta. The newborn suffered fetal distress.

CONCLUSIONS

These results show the anastomosis of at least the bilateral uterine arteries and the unilateral ovarian vein is required for uterus transplantation. This is the first report of a natural pregnancy in a primate following uterine autotransplantation.

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

STUDY QUESTION

What is the accuracy of magnetic resonance imaging (MRI) in the diagnosis of parametrial endometriosis in comparison with surgicopathological findings?

SUMMARY ANSWER

MRI displayed an accuracy of 96.4% in the preoperative diagnosis of parametrial involvement by deep infiltrating endometriosis (DIE).

WHAT IS KNOWN AND WHAT THIS PAPER ADDS

MRI is the best technique for preoperative mapping of DIE. This preliminary paper shows that T2-weighted MRI is a valuable tool for the preoperative evaluation of parametrial involvement by endometriosis.

DESIGN

A retrospective study of an MRI database was used to identify examinations performed in women, who had a clinical suspicion of pelvic endometriosis (n = 666), between 2005 and 2009 in a university medical centre in France.

PARTICIPANTS AND SETTING

Exclusion criteria were previous surgery for DIE, incomplete surgical evaluation, repeat MRI examinations and incomplete MR protocol. Only symptomatic patients who underwent surgery with a pathological correlation were included (n = 83). An experienced radiologist, blind to the surgical and histological findings, evaluated sagittal, axial and thin-section oblique axial MR images obtained from the 83 patients.

DATA ANALYSIS METHOD

Descriptive statistics and Fisher exact test were used.

MAIN FINDINGS

The prevalence of DIE and parametrial endometriosis was 76/83 (91.6%) and 12/83 (14.5%), respectively. The sensitivity, specificity, positive and negative predictive values, accuracy and positive and negative likelihood ratios for the diagnosis of parametrial endometriosis of low signal intensity on T2-weighted MRI, pelvic wall involvement and ureteral dilatation, were 83.3%, 98.6%, 90.9%, 97.2%, 96.4%, 59.2 and 0.17, 58.3%, 98.6%, 87.5%, 93.3%, 92.8%, 41.4 and 0.42 and 16.7%, 100%, 100%, 87.7%, 88%, infinity and 0.83, respectively, with the patient as the unit of analysis.

BIAS AND LIMITATIONS

The study design was retrospective, and thus prone to bias. Only one experienced reader performed the analysis, so no data are available on intra- or interobserver variability.

GENERALISABILITY

At present, no consensus exists on the optimal MR protocol to be used for the evaluation of DIE, thus limiting the wider implications of this study.

STUDY FUNDING AND COMPETING INTERESTS

No funding was obtained for this study. The authors have no conflict of interest.

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

BACKGROUND

No questionnaire is currently available for the presurgical diagnosis of adnexal torsion (AT). Our objective was to develop a predictive model for AT, based on the Self Assessment Questionnaire for Gynecologic Emergencies (SAQ-GE) designed for triaging women with acute pelvic pain.

METHODS

We performed a multicenter prospective trial conducted in five hospitals in France. Four hundred and ninety-six (496) women with acute pelvic pain (Numeric Rating Scale >4), including 31 with AT, were recruited from September 2006 through April 2008. An AT score was built using the SAQ-GE.

RESULTS

Five criteria were independently associated with AT confirmed by surgery: unilateral lumbar or abdominal pain [adjusted diagnostic odds ratio (aDOR), 23.3; 95% confidence interval (95% CI), 3.0–178]; absence of leucorrhea and metrorrhagia (aDOR, 7.0; 95% CI, 2.5–20), ovarian pain (aDOR, 5.5; 95% CI, 1.5–21), unbearable pain (aDOR, 5.0; 95% CI, 1.4–18) and vomiting (aDOR, 3.7; 95% CI, 1.6–9.0). The SAQ-GE torsion score was based on these five criteria and its values range from 0 to 10. The low-risk group (SAQ-GE torsion score <7), based on the score values, has a sensitivity (Se) of 96.7% (95% CI, 90.5–100), a negative predictive value of 99.7% (95% CI, 99.1–100) and a negative likelihood ratio (Lr–) of 0.05, ruling out AT with a probability of AT of 0.3% (95% CI, 0.0–0.9). Cross-validation of the model was performed using the jackknife resampling procedure, retrieving an unbiased Se of 87.1 (95% CI, 75.1–99.1) and a specificity of 74.2% (95% CI, 70.2–78.2).

CONCLUSIONS

The SAQ-GE torsion score may prove useful for screening for AT in patients experiencing acute pelvic pain.

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

STUDY QUESTION

Does follicular flushing during assisted reproductive technologies (ART) improve the number of oocytes retrieved?  

SUMMARY ANSWER

Follicular flushing during ART does not result in a greater number of oocytes in normal responders.

WHAT IS KNOWN ALREADY

Despite limited evidence supporting the use of follicular flushing, it continues to be a common procedure in many ART clinics. Prior studies have provided conflicting results regarding the routine use of flushing during oocyte retrieval.

STUDY DESIGN, SIZE, DURATION

Systematic review and meta-analysis of 518 patients who participated in 6 randomized trials over 20 years.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Literature searches were conducted to retrieve randomized controlled trials on follicle or ovarian flushing in ART. Databases searched included PubMed, EMBASE, Web of Science and the Cochrane Database of Clinical Trials (CENTRAL). Six trials that included 518 subjects matched the inclusion criteria. Studies included were limited to trials that were published, randomized trials comparing oocyte retrieval with a single-lumen pick-up needle versus follicle flushing after direct aspiration with a multi-channel oocyte pick-up needle in ART patients.

MAIN RESULTS AND THE ROLE OF CHANCE

In each of the trials, measures of the oocyte yield (oocytes retrieved divided by follicles aspirated), total oocytes retrieved, fertilization or pregnancy were not different when comparing direct aspiration with follicle flushing. Four trials reported a higher operative time with follicle flushing. Results of the meta-analysis indicated no significant differences in the oocytes retrieved [weighted mean difference: 0.07, 95% confidence interval (CI): –0.13 to 0.29] or the oocyte yield (odds ratio: 1.06, 95% CI: 0.95–1.18) between the non-flushing and flushing groups.

LIMITATIONS, REASONS FOR CAUTION

All trials featured an open label design and the majority of patients in this meta-analysis were normal responders. The applications of these results to poor responders, patients undergoing natural cycle ART or minimal stimulation ART should be made with caution.

WIDER IMPLICATIONS OF THE FINDINGS

Follicle flushing does not improve ART outcomes in normal-responding patients and should not be performed. This meta-analysis should solidify this recommendation as it includes the largest trial published on the subject and is consistent with a recently published Cochrane review.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD. The authors have no competing interests to declare.

TRIAL REGISTRATION NUMBER

N/A.

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

STUDY QUESTION

What is the rate of spontaneous live births after successful IVF treatment in a cost-free environment, and were couples who achieved a spontaneous live birth referred prematurely?

SUMMARY ANSWER

Despite unlimited IVF treatments offered free of charge, the spontaneous live birth rate following successful IVF remained unchanged compared with that cited in previous literature. Couples were not referred prematurely to IVF before fully utilizing other less invasive treatments.

WHAT IS KNOWN ALREADY

A significant number of infertile couples, who achieve their first live birth through assisted reproductive technology (ART), subsequently achieve a second live birth spontaneously. As IVF has become more widely available, it is used in less severe cases of infertility, perhaps explaining a rise in the subsequent spontaneous live birth rate after successful treatments.

STUDY DESIGN, SIZE, DURATION

This retrospective cohort study was performed at a university-based tertiary medical center. The study population included women aged <35 years, with primary infertility, referred for their first IVF treatment to the Sheba Medical Center IVF unit between 2001 and 2002 and followed up for 7 years. The primary outcome was spontaneous live birth rate following successful ART. Relevant data were obtained from the patient files and supplemented by a standardized telephone questionnaire.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Of the 171 couples who met the study inclusion criteria, 6 refused to participate in the questionnaire and 31 couples were lost to follow-up. Of the 134 couples who participated, 109 achieved a first live birth with ART. After achieving their first live birth with ART, seven couples who began using contraception or separated or divorced were excluded.

MAIN RESULTS AND THE ROLE OF CHANCE

Of 102 couples who continued unprotected intercourse after successful ART, 22 subsequently achieved their second live birth spontaneously (21.6%). The women who achieved a second birth spontaneously were not referred earlier to IVF, and actually performed a higher number of ovulation induction cycles before initiating IVF, compared with women who did not conceive spontaneously.

LIMITATIONS, REASONS FOR CAUTION

This is a retrospective cohort study, and findings should be reaffirmed with a larger prospective randomized study comparing retreatment to achieve a second pregnancy with attempting to conceive spontaneously.

WIDER IMPLICATIONS OF THE FINDINGS

Our data suggests that young patients (<35 years), who previously conceived with IVF, without utilizing ICSI and with no known tubal pathology, should consider attempting to conceive spontaneously.

STUDY FUNDING AND COMPETING INTEREST(S)

No funding was obtained for this study and the authors have no competing interests.

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

BACKGROUND

The incidence of overweight and obesity in men of reproductive ages is rising, which may affect fertility. Therefore, this study aims to assess the associations between BMI, central adiposity and sperm parameters in men of subfertile couples.

METHODS

Ejaculate volume (ml), sperm concentration (millions per ml), percentage of progressive motile and immotile spermatozoa and total motile sperm count (millions) were measured in 450 men of subfertile couples visiting a tertiary outpatient clinic for reproductive treatment and preconception counseling.

RESULTS

Overweight was negatively associated with the percentage of progressive motility type A [β –0.32 (SE 0.2), P = 0.036] and positively associated with the percentage of immotility type C [β 0.21 (SE 0.07), P = 0.002]. Obesity was negatively associated with ejaculate volume [β –0.23 (SE 0.1), P = 0.02], sperm concentration [β –0.77 (SE 0.3), P = 0.006] and total motile sperm count [β –0.91 (SE 0.3), P = 0.007]. Waist circumference ≥102 cm, a measure for central adiposity, was inversely associated with sperm concentration [β –0.69 (SE 0.2), P = 0.001] and total motile sperm count [β –0.62 (SE 0.3), P = 0.02]. All associations remained significant after adjustment for age, ethnicity, active and passive smoking, alcohol and medication use and folate status.

CONCLUSIONS

This study shows that in particular, sperm concentration and total motile sperm count in men of subfertile couples are detrimentally affected by a high BMI and central adiposity. The effect of weight loss on sperm quality and fertility needs further investigation.

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

OBJECTIVES AND AIM

IVF has become an efficient and widely used treatment for infertile couples, however, it is responsible for an increasing number of multifetal pregnancies and adverse neonatal outcomes. This study aimed to assess a health service utilization in one neonatal intensive care unit (NICU), as a response to the 2010 Turkish reproductive regulation requiring single embryo transfer (SET).

METHODS

All assisted reproductive technology (ART) pregnancies delivered at Zekai Tahir Burak Maternity Teaching Hospital between February 2010 and October 2011 were included in this study. Subjects were divided into two groups: Group 1 consisted of infants conceived before the ART regulation, and born between February 2010 and October 2010, and Group 2 consisted of infants conceived after the ART regulation, and born between November 2010 and October 2011.

RESULTS

Upon comparing the study groups, we observed a significant decrease in the incidence of multiple births in Group 2. The mean gestational age and mean birthweight were significantly higher in Group 2. The rates of prematurity and low birthweight, very low birthweight and extremely low birthweight infants were significantly lower in Group 2. Similarly, the rates of NICU admission, respiratory distress syndrome, necrotizing enterocolitis anemia and pneumonia/sepsis, and the need for respiratory support (mechanical ventilation and nasal continuous positive airway pressure) were significantly lower in Group 2.

CONCLUSIONS

According to our data, NICU utilization was reduced and the early post-natal outcomes of the babies were improved after the new Turkish regulation on ART imposing SET. However, multicenter studies are needed to generalize our results to the whole country.

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

BACKGROUND

More couples are delaying childbirth resulting in an increase of age-related subfertility in women. Subfertility and assisted reproductive technology (ART) treatments may affect couples' psychological well-being. The aim of the present study was to investigate whether factors related to IVF/ICSI affect anxiety and mental health in couples 1 year after childbirth.

METHOD

In this cohort study, we included couples with a singleton pregnancy following IVF/ICSI treatment (n = 113) and subfertile couples who naturally conceived (NC; n = 83). Parental trait anxiety (Dutch version of the Spielberger State-Trait Anxiety Inventory) and mental health (Dutch version of General Health Questionnaire) were assessed 1 year after childbirth. The influence of fertility-related factors was analyzed with logistic regression analyses.

RESULTS

One hundred and ninety-six couples participated, 93% of those eligible. Trait anxiety and mental health were similar in IVF/ICSI and NC groups. However, NC fathers had more often mental health scores in the clinical range (21%) than fathers in the IVF/ICSI group (9%). The risk of having a trait anxiety or mental health score in the clinical range was reduced by the presence of one of the following factors: for females a higher number of IVF/ICSI treatment cycles, and a maternal cause of subfertility, for males having been treated by IVF/ICSI and a longer time to pregnancy.

CONCLUSIONS

The present study indicates (i) that IVF/ICSI treatment is not associated with an increase in clinically relevant Spielberger State-Trait Anxiety Inventory and General Health Questionnaire scores in parents 1 year after childbirth and (ii) a higher number of IVF/ICSI treatment cycles and a longer time to pregnancy were associated with less trait anxiety and better mental health. A limitation of the study is the absence of mental health and trait anxiety data at baseline.

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

BACKGROUND

Lifestyle has been shown to affect fertility in both males and females, with compelling evidence that smoking and being under or overweight impairs natural and assisted fertility, and other factors such as stress and caffeine have also been implicated. The objective of this study was to determine whether providing infertile couples with individualized lifestyle assessments and ongoing support facilitates positive lifestyle changes enhancing healthy fertility.

METHODS

We conducted a prospective cohort pilot study of 23 infertile couples attending an Adelaide-based fertility clinic for advice and treatment relating to infertility. The intervention was a comprehensive assessment interview with the couple, focused on health and lifestyle. Motivational interviewing techniques were used and ongoing support provided. The assessment was repeated after 4 months and included an exit questionnaire. The main outcome measure(s) was self-reported lifestyle changes, including increased exercise, modified diet, reduced caffeine and alcohol consumption, ceased or reduced smoking and decreased psychological stress.

RESULTS

Following the initial lifestyle assessment interview, all participants reported adverse lifestyle behaviour.

CONCLUSIONS

The results suggest that the FAST (Fertility ASsessment and advice Targeting lifestyle choices and behaviours) approach of an individualized assessment of current lifestyle practice followed by ongoing one to two weekly telephone support is effective in promoting healthy lifestyle change. Larger studies using this methodology are now required.

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

STUDY QUESTION

What are the childbearing intentions of currently childless men and women? What is their attitude towards, and willingness to use, assisted human reproduction (AHR) treatments and family-building options should they be faced with fertility challenges in the future?

SUMMARY ANSWER

Men and women expect to become parents significantly later in life than they believe is ideal. If faced with future fertility challenges, respondents were open to using IVF, but were not positively predisposed to third-party family-building options.

WHAT IS KNOWN ALREADY

Delayed childbearing is an increasing worldwide phenomenon that has considerable health and fertility-related implications. Research to date has focused primarily on women, and indicates a lack of knowledge about the fertility life span and the limitations of AHR in fully compensating for age-related fertility declines.

STUDY DESIGN, SIZE, DURATION

Cross-sectional study of 2000 childless women and 599 childless men, conducted between April 2010 and May 2011.

PARTICIPANTS/MATERIALS, SETTING, METHODS

A total of 2599 childless, presumed fertile individuals between the ages of 20 and 50 years. An online questionnaire assessed fertility beliefs and intentions and willingness to use AHR.

MAIN RESULTS AND THE ROLE OF CHANCE

The findings indicate that men and women expect to become parents significantly later in life than they believe is ideal. If faced with fertility challenges in the future, both men and women were open to using IVF. Men were significantly more willing to consider using donated eggs and embryos, gestational surrogacy and fertility preservation. Women were significantly more willing to consider using home fertility testing, IVF, ICSI and donor sperm. Overall, the childless respondents were not positively predisposed to third party-family-building options.

LIMITATIONS

The geographic specificity of the sample, the online format and recruitment methods may limit the generalizability of these findings.

WIDER IMPLICATIONS OF THE FINDINGS

Given the worldwide trend towards delayed childbearing, and the widespread availability of AHR, it is likely that these findings could extend to the wider North American, European and Australasia populations of English- and French-speaking childless men and women. However, it should be noted that international differences exist, especially concerning regulations governing the funding of AHR and payment for gametes and surrogacy. It is significant that women and men in this study indicated a lack of willingness to consider the use of third third-party treatments—the very options they may need to use in building their families, if the increasing trend towards delayed childbearing continues.

STUDY FUNDING/COMPETING INTERESTS

This research was funded by a grant from the Canadian Institutes of Health Research and Assisted Human Reproduction Canada #PAH-103594, 2009/10. No competing interests.

Source:
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Published on 09 July 2012 Hits: 79

ROME: The number of babies born as a result of assisted reproduction technologies (ART) has reached an estimated total of 5 million, according to information presented at the 28th annual meeting of the European Society of Human Reproduction and Embryology (Eshre), which opened on July 1, in Istanbul, Turkey.

According to the July 2 press release from Eshre the estimate comes from Icmart (International Committee for Monitoring Assisted Reproductive Technologies) and was based on the number of In Vitro Fertilizations (IVF) and Iintracytoplasmic Sperm Injection (ICSI) treatment cycles recorded worldwide up to 2008 with projections added for the following three years.

Dr. David Adamson, of Fertility Physicians of Northern California, USA, and chairman of Icmart, said about 1.5 million ART cycles are now performed globally each year, producing around 350,000 babies.

The news came shortly after the death of Lesley Brown, 64, who lived in Bristol, England, and made history in July 1978 when her daughter Louise was the first child to be born as the result of IVF treatment.

Lesley Brown had two daughters, Louise and Natalie, both born following IVF treatment, the BBC reported June 20.

In reaction to the latest news on IVF babies Anthony Ozimic, communications director for the English Society for the Protection of Unborn Children, said that What is largely overlooked is that many millions more embryonic children have been killed following IVF, a quality-controlled process which is also intrinsically abusive of human beings.

If the countless millions of pounds given to IVF had been given to the much-more successful ethical alternatives, many more children would have been born, he added.

Health risks In a July 3 press release Irelands Iona Institute pointed out that a recent Australian study has revealed serious health risks for those using IVF.

An Australian study, published in the journal Fertility and Sterility, found that women who went through the IVF procedure around their 24th birthday were found to have a 56 percent greater chance of developing breast cancer than those in the same age group who went through treatments without IVF.

Excerpt from:
The hidden costs of reproductive technology

Public release date: 4-Jul-2012 [ | E-mail | Share ]

Contact: Christine Bauquis christine@eshre.eu 32-499-258-046 European Society of Human Reproduction and Embryology

Istanbul, 4 July 2012: There is growing interest in a "freeze-all" embryo policy in IVF. Such an approach, which cryopreserves all embryos generated in a stimulated IVF cycle for later transfer in a non-stimulated natural cycle, would avoid any of the adverse effects which ovarian stimulation might have on endometrial receptivity during the treatment cycle. Ovarian stimulation has been shown to have adverse effects on endometrial receptivity and the risk of ovarian hyperstimulation syndrome (OHSS) is also increased when embryo transfer is performed in the stimulated cycle.

Freezing all embryos for later transfer might therefore improve implantation and pregnancy rates and increase the safety of IVF. Presently, the highest success rates in reproductive medicine are seen in the recipients of donor eggs. These are women who have not had ovarian stimulation - their endometrial tissue has not been exposed to high hormone levels, and they are not at risk of OHSS.

However, while the theory of a freeze-all policy seems attractive - and the technique has been commonly employed as a safety measure when OHSS is a threat - no robust systematic studies have indicated whether the cryopreservation of all viable embryos with later frozen embryo transfer (FET) is associated with better outcomes than fresh embryo transfers.

Now, the first meta-analysis on this subject indicates that the chance of a clinical pregnancy is around 30% higher when all embryos are frozen for later transfer than with fresh embryo transfer. The results were presented today at the annual meeting of ESHRE (European Society of Human Reproduction and Embryology) by Professor Miguel Angel Checa from the Hospital Universitari del Mar in Barcelona, Spain.

The study was a systematic review of the entire literature, which provided a pool of 64 relevant studies - with three randomised trials - performed before December 2011. The current review was based on information from 633 IVF/ICSI cycles in which 316 were randomised to fresh embryo transfer and 317 to FET. Results showed - based on a relative risk calculation - that the probability of a clinical pregnancy is significantly higher from freeze-all cycles than in fresh embryo transfers (a relative risk of 1.31, which was statistically significant). The miscarriage rates did not show significantly differences between the two groups.

"The pooled data demonstrates that embryo cryopreservation and subsequent FET may improve the outcome of assisted reproduction treatment," said Professor Checa. The study recorded an ongoing pregnancy rate of 38% in fresh transfer cycles, and 50% in the FET cycles.

Professor Checa also explained why FET in a later non-stimulated cycle might improve IVF results. He noted that the multiple eggs generated by ovarian stimulation will increase release of the hormone estradiol from the ovary, which affects the receptivity of endometrial tissue. In addition, some recent studies have shown that ovarian stimulation causes changes to the endometrial DNA pattern, which are not evident in the normal receptive endometrium.

Professor Checa added that the results of his study were "preliminary", but statistically robust. However, with other groups known to be performing similar studies, he urged patience until their results were known. "We are quite confident with our results," he said. "But in our view we should wait until the end of the year for results from other studies to confirm our data and recommend a change in IVF policy."

More:
Freezing all embryos in IVF with transfer in a later non-stimulated cycle may improve outcome

Public release date: 4-Jul-2012 [ | E-mail | Share ]

Contact: Christine Bauquis christine@eshre.eu 32-499-258-046 European Society of Human Reproduction and Embryology

Istanbul, 4 July 2012: A policy of single embryo transfer (SET) reduces the risk of perinatal mortality in infants born as a result of IVF and ICSI. The conclusion emerged from an analysis of more than 50,000 births recorded in the Australian and New Zealand Assisted Reproduction Technology Database between 2004 and 2008, where the introduction of an SET policy has been associated with a reduction in overall perinatal mortality for IVF and ICSI babies.

Results of the analysis were presented here today at the annual meeting of ESHRE (European Society of Human Reproduction and Embryology) by Professor Elizabeth Sullivan from the Perinatal & Reproductive Epidemiology Research Unit of the University of New South Wales in Sydney, Australia. Professor Sullivan said that from a public health perspective "there is justification for advocating SET as first line management in assisted reproduction with the aim of minimising preventable perinatal deaths".

The study she described included 50,258 births which were of more than 20 weeks gestation and/or 400 grams birthweight following IVF and ICSI pregnancies. Total perinatal deaths were defined as the number of fetal deaths (stillbirths) plus the number of neonatal deaths (deaths that occur before 28 days after birth).

Analysis showed an overall perinatal mortality rate of 16.2 per 1000 births, representing 813 perinatal deaths during the study period (630 stillbirths and 183 neonatal deaths).

However, births following the transfer of two embryos had a significantly higher perinatal mortality rate than births following SET (19.1 per 1000 births and 13.2 per 1000 births). The risk of perinatal mortality for all births following two embryo transfer was 53% higher than those following SET. This difference was especially apparent in births following the transfer of fresh (and not frozen) embryos; births following the transfer of two fresh embryos had 74% higher risk of perinatal mortality than births following fresh SET.

Twins accounted for half the total neonatal deaths and one-third the perinatal deaths. Twins also had significantly higher perinatal mortality rate than singletons (27.8 per 1000 births and 12.4 per 1000 births). However, twins born from SET (ie, monozygotic) had a higher risk of perinatal mortality than those born from two embryo transfers.

Professor Sullivan noted that the voluntary adoption of an IVF policy of single embryo transfer in Australia and New Zealand has been associated with a reduction in overall perinatal mortality for all babies conceived by assisted reproduction methods, which was justification in itself for recommending SET as a first line fertility treatment for non-donor cycles in women aged under 35 years.

Moreover, said Professor Sullivan, there are wider public health benefits from an SET policy. She explained: "The number of embryos transferred per procedure is the major determinant of multiple pregnancy and multiple delivery, which contribute to an elevated risk of preterm birth and low birth weight, and its sequelae. These are risks in addition to those already faced by women being treated for infertility.

Continue reading here:
Single embryo transfer reduces the risk of perinatal mortality in IVF