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Functional attenuation of human sperm by novel, non-surfactant spermicides: precise targeting of membrane physiology without affecting structure

Posted: April 14, 2010 at 8:20 am

BACKGROUND

We have attempted to identify structural, physiological and other targets on human sperm vulnerable to the spermicidal action of two novel series of non-detergent molecules, reported to irreversibly immobilize human sperm in <30 s, apparently without disrupting plasma membrane.

METHODS

Three sperm samples were studied. Scanning and transmission electron microscopy were used to assess structural aberrations of sperm membrane; plasma membrane potential and intracellular pH measurements (fluorometric) were used to detect changes in sperm physiology; reactive oxygen species (ROS, fluorometric) and superoxide dismutase activity (colorimetric) were indicators of oxidative stress; and sperm dynein ATPase activity demonstrated alterations in motor energy potential, in response to spermicide treatment. Post-ejaculation tyrosine phosphorylation of human sperm proteins (immunoblotting) was a marker for functional integrity.

RESULTS

Disulfide esters of carbothioic acid (DSE compounds) caused complete sperm attenuation at ≥0.002% concentration with hyper-polarization of sperm membrane potential (P < 0.001), intracellular alkalinization (P < 0.01), ROS generation (P < 0.05) and no apparent effect on sperm (n = 150) membrane structure. Isoxazolecarbaldehyde compounds required ≥0.03% for spermicidal action and caused disrupted outer acrosomal membrane structure, depolarization of membrane potential (P < 0.001), intracellular acidification (P < 0.01) and ROS generation (P < 0.01). Detergent [nonoxynol-9 (N-9)] action was sustainable at ≥0.05% and involved complete breakdown of structural and physiological membrane integrity with ROS generation (P < 0.001). All spermicides caused functional attenuation of sperm without inhibiting motor energetics. Unlike N-9, DSE-37 (vaginal dose, 200 µg) completely inhibited pregnancy in rats and vaginal epithelium was unchanged (24 h,10 mg).

CONCLUSIONS

The study reveals a unique mechanism of action for DSE spermicides. DSE-37 holds promise as a safe vaginal contraceptive.

CDRI Communication No. 7545.

Recommendation and review posted by Guinevere Smith

Characteristics indicating adenomyosis coexisting with leiomyomas: a case-control study

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Adenomyosis is rarely diagnosed before hysterectomy and commonly coexists with uterine leiomyomas. The objective of this study was to identify distinct features of a concurrent diagnosis of adenomyosis in women with uterine leiomyomas.

METHODS

We conducted a case–control study of women undergoing hysterectomy with a histologic diagnosis of both adenomyosis and leiomyomas and women with uterine leiomyomas but no adenomyosis. A retrospective medical record review of hospital and ambulatory records was performed to ascertain sociodemographic and anthropometric variables, as well as to confirm intraoperative and pathologic findings.

RESULTS

Our study sample comprised 255 patients, 85 women with adenomyosis and leiomyomas and 170 women with only leiomyomas. In multivariable logistic regression analyses, women with adenomyosis and leiomyomas were more likely to have more pelvic pain [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.8–6.4], have less fibroid burden (OR per doubling in fibroid size 0.6, 95% CI 0.5–0.8), were more likely to be parous (OR 3.8, 95% CI 1.4–10.5) and have lower body mass index (OR per 5 unit increase in BMI 0.8, 95% CI 0.6–1.0) when compared with women with leiomyomas alone.

CONCLUSIONS

Women undergoing hysterectomy with both adenomyosis and leiomyomas have a number of different clinical features compared with women with only leiomyomas at the time of hysterectomy. Women with substantial pain despite a smaller fibroid burden may be more likely to have concomitant adenomyosis.

Recommendation and review posted by Guinevere Smith

The risk of post-molar gestational trophoblastic neoplasia is higher in heterozygous than in homozygous complete hydatidiform moles

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Complete hydatidiform mole (CHM) is a high-risk pregnancy for gestational trophoblastic neoplasia (GTN). Patients with CHM have a 10–30% chance of trophoblastic sequelae. CHM includes androgenic homozygous (monospermic) and androgenic heterozygous (dispermic) moles. It is controversial whether the risk of GTN is higher with heterozygous than with homozygous CHM. A prospective cohort study was conducted to assess risk of GTN in homozygous and heterozygous CHM using short tandem repeat (STR) polymorphisms, and a meta-analysis of previous reports.

METHODS

Twenty-eight consecutive molar pregnancies were evacuated and followed by regular hCG measurements to detect GTN. Persistent GTN was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 system. Cytogenesis of the mole was determined by STR polymorphisms of molar tissue and parental blood. A meta-analysis of the GTN rate from previous reports was conducted using Mantel–Haenszel methods.

RESULTS

Of 28 molar pregnancies, 24 were homozygous and three were heterozygous CHM. The remaining mole was diandric triploidy (a partial hydatidiform mole). Of the 24 homozygous CHMs, six (25%) cases developed GTN and received chemotherapy. Meanwhile, all three cases (100%) of heterozygous mole developed GTN and needed chemotherapy. The GTN risk was higher in heterozygous (P = 0.029, Fisher’s exact test) than homozygous moles. A systematic review revealed only five previous reports (with more than 15 cytogenetically diagnosed cases), and the pooled relative risk of persistent GTN for heterozygous mole was not significant (odds ratio, 2.0; 95% confidence interval, 0.98–4.07).

CONCLUSIONS

Heterozygous CHM had a higher risk for GTN than homozygous CHM.

Recommendation and review posted by Guinevere Smith

Cumulative ongoing pregnancy rate achieved with oocyte vitrification and cleavage stage transfer without embryo selection in a standard infertility program

Posted: April 14, 2010 at 8:20 am

BACKGROUND

Recent advancement of minimum volume vitrification methods has resulted in a dramatic increase in the efficiency of the process. The aim of this study was to estimate the cumulative reproductive outcome of a cohort of infertile couples undergoing ICSI and oocyte vitrification in restrictive legal conditions, where only a limited number of oocytes could be inseminated per cycle and embryo selection and cryopreservation were forbidden.

METHODS

In this prospective longitudinal cohort study, the cumulative ongoing pregnancy rates obtained by the insemination of fresh and vitrified oocytes from the same cohort were calculated as primary outcome measures. Moreover, the effect of basal and cycle characteristics on clinical outcomes were assessed.

RESULTS

Between September 2008 and May 2009, 182 ICSI cycles were performed where oocyte vitrification was possible. A total of 104 first and 11 second oocyte warming cycles were then performed in non-pregnant patients of the same cohort. The overall ongoing pregnancy rates obtained in the fresh, and first and second warming cycles were 37.4, 25.0 and 27.3%, respectively. The overall cumulative ongoing clinical pregnancy rate observed per stimulation cycle was 53.3%. Maternal age was the only characteristic found to influence the reproductive outcome, with an inverse correlation between the age >40 and the ongoing pregnancy rates (P = 0.04, by Cox regression analysis).

CONCLUSIONS

High cumulative ongoing pregnancy rates can be obtained with transfers of embryos derived from fresh and cryopreserved oocytes in a typical infertile population. Female age significantly affects outcomes in this system.

Recommendation and review posted by Guinevere Smith

Pregnancy outcome in female childhood cancer survivors

Posted: April 14, 2010 at 8:20 am

BACKGROUND

The number of childhood cancer survivors has dramatically increased and consequently, an increasing number of survivors may now wish to conceive. Recently, several studies have described that previous treatment with abdominal radiotherapy may increase the risk of adverse pregnancy outcome.

METHODS

We conducted a retrospective single centre cohort study of childhood cancer survivors with a singleton live birth between January 2000 and December 2005. Pregnancy outcome was compared with data from the Netherlands Perinatal Registry, a nationwide database of pregnancy outcome parameters of all births in the Netherlands registered by midwives, obstetricians and paediatricians.

RESULTS

Data were available on 40 survivors and 9031 controls. Median age at diagnosis was 6.9 years (range 0.1–16.8 years). The median interval between diagnosis and date of delivery was 21.6 years (range 7.4–36.1 years). In the whole cohort, pregnancy outcome was not different between survivors and controls. However, survivors treated with abdominal radiotherapy delivered preterm and had post-partum haemorrhage (mean gestational age in survivors = 34.9 versus 39.2 weeks in controls, P = 0.001; 33% in survivors versus 5% in controls, P = 0.007, respectively). The offspring of survivors had normal birthweight after adjustment for gestational age (mean birthweight in offspring of survivors 2503 versus 1985 g; P = 0.22).

CONCLUSION

Childhood cancer survivors irradiated to the abdomen have an earlier delivery and higher incidence of post-partum haemorrhage. This stresses the need for close monitoring of the delivery, including inpatient perinatal care, in this group of childhood cancer survivors.

Recommendation and review posted by Guinevere Smith

Offering excess oocyte aspiration and vitrification to patients undergoing stimulated artificial insemination cycles can reduce the multiple pregnancy risk and accumulate oocytes for later use

Posted: April 14, 2010 at 8:20 am

BACKGROUND

The prevention of multiple pregnancies remains a major challenge in patients treated with ovarian stimulation prior to intrauterine insemination (IUI). The pilot study presented here investigates whether multiple pregnancies can be minimized by a microscopically confirmed aspiration of oocytes from supernumerary follicles immediately before intrauterine insemination and evaluates the benefit of concomitant excess oocyte cryopreservation for future use.

METHODS

Thirty-four aspirations of supernumerary follicles were performed immediately prior to IUI in 31 patients undergoing ovarian stimulation. sIUI was only performed if cumulus-oocyte complexes were microscopically observed in the aspirated follicular fluid. All collected mature excess oocytes were cryopreserved using the vitrification technique.

RESULTS

Only four sIUI procedures had to be cancelled due to failed oocyte retrieval or premature ovulation. IUI treatment resulted in a clinical pregnancy rate of 23.5% per cycle. All were singleton pregnancies. A total of 111 oocytes were cryopreserved. Patients with polycystic ovary syndrome (PCOS) had an average of 6.07 oocytes vitrified, whereas patients without PCOS had 1.3 oocytes vitrified per cycle.

CONCLUSION

Microscopically confirmed collection of excess oocytes prior to stimulated IUI reduced cancellation rates, further reduced the risk for multiple pregnancy and may lead to future additional pregnancies because, based on current information, approximately 5% of the vitrified oocytes could potentially establish a pregnancy.

Recommendation and review posted by Guinevere Smith


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