When using donor oocytes,does embryo stage matter? An analysis of blastocyst versus cleavage stage embryo transfers using a cryopreserved donor oocyte bank

Journal of Assisted Reproduction and Genetics - Oocyte donor in vitro fertilization (IVF) represents an ideal model to study the effects of embryo stage on reproductive success, as embryos come...     

G2/M transition of pig oocytes: How do oocytes initiate maturation?

In the ovary, mammalian oocytes resume meiosis and mature to the second metaphase when they are stimulated with gonadotrophins. Similarly, oocytes can mature in vitro when they are liberated from ovarian follicles and cultured under appropriate conditions. Early in the process of maturation, oocytes undergo dramatic but well-ordered changes at the G2/M transition in the cell cycle including: (i) chromosome condensation; (ii) nucleolus disassembly; (iii) germinal vesicle breakdown (GVBD); and (iv) spindle formation in the first metaphase (MI-spindle). These events have been thought to be induced by MPF (maturation-promoting factor or M-phase promoting factor), now known as Cdc2 kinase or Cdk1 kinase, which consists of a catalytic subunit, Cdc2, and a cyclin B regulatory subunit. In fact, nuclear lamins are phosphorylated by Cdc2 kinase, and nuclear membrane breakdown occurs concomitantly with the activation of Cdc2 kinase in the M-phase of both somatic cells and oocytes. Based on the classical and recent studies of the pig oocyte, however, the chromosomes start to condense and the nucleolus disassembles before full activation of Cdc2 kinase, and the MI-spindle is formed after activation of both Cdc2 kinase and MAP kinase; another kinase known to become activated during oocyte maturation. These findings suggest that chromosome condensation and nucleolus disassembly in oocytes are induced by either some kinase(s) other than Cdc2 kinase and MAP kinase or some phosphatase(s). The accumulation of new results regarding the molecular nature of oocyte maturation is important for improving the reproductive technologies in domestic animals as well as in humans. (Reprod Med Biol 2003; 2 : 91–99)     

How much is another randomized trial of lymph node dissection in endometrial cancer worth? A value of information analysis

Objective

This study aimed to assess the value of a randomized controlled trial (RCT) of lymph node dissection (LND) at the time of hysterectomy for high-risk subsets of women with endometrial cancer.

Methods

A modified Markov decision model compared routine LND to no LND for women with grade 3 or grades 2–3 endometrial cancer. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity and value of information (VOI) analyses. Survival without LND was modeled from Surveillance, Epidemiology and End Results program data. A hazard ratio (HR) describing survival in the high-risk group undergoing LND (estimate 0.9, 95% CI 0.6–1.1), adverse event rates, probability and type of adjuvant therapy were modeled from published RCTs. Costs were obtained from national reimbursement data. VOI estimated the value of reducing uncertainty regarding the survival benefit of LND.

Results

For grade 3, LND had an incremental cost-effectiveness ratio of $40,183/quality-adjusted life year (QALY) compared to no LND. Acceptability curves revealed considerable uncertainty, with an expected value of perfect information of $4,195 per patient at societal willingness to pay of $50,000/QALY. The estimated value of partial perfect information regarding the HR was $3,702 per patient. Assuming 8,000 individuals annually with grade 3 endometrial cancer in the US, the upper limit of VOI for the HR was $29.6 million annually. For grades 2 and 3 combined, analysis revealed a much lower likelihood of finding LND cost-effective.

Conclusion

A clinical trial defining the survival effect of LND in women with grade 3 endometrial cancer is a worthwhile use of resources.     

How long is too long: Does a prolonged second stage of labor in nulliparous women affect maternal and neonatal outcomes?

OBJECTIVE: The purpose of this study was to examine maternal and neonatal outcomes in relation to lengthening intervals of the second stage of labor. STUDY DESIGN: This is a retrospective cohort study of 15,759 nulliparous, term, cephalic, singleton births at the University of California, San Francisco, between 1976 and 2001. The second stage of labor was divided into 1-hour intervals. Maternal and neonatal outcomes were compared with the use of chi-squared and Student t tests, and a probability value of < or =.05 was used to indicate statistical significance. Potential confounders were controlled for with multivariate logistic regression. RESULTS: Increasing rates of cesarean delivery, operative vaginal delivery, and perineal trauma were associated with the second stage beyond the first hour. In multivariate analysis, the >4-hour interval group had higher rates of cesarean delivery (odds ratio, 5.65; P < .001), operative vaginal deliveries (odds ratio, 2.83; P < .001), 3rd- or 4th-degree perineal lacerations (odds ratio, 1.33; P = .009), and chorioamnionitis (odds ratio, 1.79; P < .001). There were no differences in neonatal acid-base status associated with length of second stage. However, there were fewer neonates with a 5-minute Apgar score of <7 (odds ratio, 0.45; P = .01). CONCLUSION: Although the length of the second stage of labor is not associated with poor neonatal outcome, a prolonged second stage is associated with increased maternal morbidity and operative delivery rates.     

Preoperative staging of cervical cancer: is 18-FDG-PET/CT really effective in patients with early stage disease?

Objective

Nodal status is one of the most important findings in patients with early-stage cervical cancer that requires post-surgical adjuvant therapies and influences prognosis of patients. The purpose of this study was to determine the diagnostic accuracy of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) in the detection of nodal metastases.

Methods

From 2004 to 2010 women with Ib1–IIa < 4 cm cervical cancer underwent 18F-FDG-PET/CT followed by radical hysterectomy and pelvic lymphadenectomy in our institution. 18F-FDG-PET/CT images were analyzed and histopathological findings served as the reference standard. Diagnostic performance of 18F-FDG-PET/CT in nodal disease detection was reported in terms of accuracy value. A sub analysis of women with tumor diameter < 2 cm (group 1) or 2–4 cm (group 2) was performed in order to verify the efficacy of 18F-FDG-PET/CT in each group.

Results

One hundred fifty-nine women were enrolled. 65% had squamous histotype and 51% had grade 3 disease. Median number of nodes dissected was 29 (range 11–61). 28/159 women (18%) showed nodal metastases. Overall patient-based sensitivity, specificity, positive and negative predictive value of 18F-FDG-PET/CT for detection of nodal disease were 32.1%, 96.9%, 69.2%and 87.0% respectively.Among the 97 (61%) women included in group 1, 8 had nodal metastases (8.2%) and 2 was discovered through 18F-FDG-PET/CT (25%), while 20/62 women of the group 2 (32.3%) had nodal involvement, of which 7 (35%) was detected by 18F-FDG-PET/CT.

Conclusions

This study showed that 18F-FDG-PET/CT had low sensitivity and had a minimal clinical impact in the pretreatment planning of stage Ib1–IIa < 4 cm cervical cancer.     

How distressing is referral to colposcopy in cervical cancer screening?: A prospective quality of life study

Objective

Referral for colposcopy because of abnormal Pap test results is likely to be distressing, but the extent and duration of these effects are unknown. We aimed to fill this gap.

Methods

We conducted a prospective observational study at two departments of Obstetrics and Gynecology (an academic and a non-academic setting). Women referred for colposcopy completed questionnaires before colposcopy, and at 1, 3, and 6 months afterwards. A reference group of 706 screen participants, aged 29–60 years old, was included and completed questionnaires once. Main outcome measures were generic health-related quality of life (HRQoL), assessed through the EQ-5D and the SF-12 physical and mental scores (PCS-12 and MCS-12); anxiety as assessed by STAI-6, and screen-specific anxiety as assessed by the psychological consequences questionnaire (PCQ).

Results

154 women responded to the questionnaire, of whom 132 were included in the analyses. Histological results were CIN 1 in 17/115 women (15%) and CIN 2 + in 62 (54%). In 36 women (31%) there was no histologically confirmed neoplasia. Before colposcopy physical HRQoL scores were similar or slightly better than in the reference group, while mental HRQoL (MSC-12) and (screen-specific) anxiety were worse (p < 0.001). Irrespective of CIN-grades, anxiety washed out during follow-up (p < 0.001), with changes being clinically relevant.

Conclusions

Referral for gynecological evaluation because of abnormal PAP-test results was distressing. Anxiety – and not the physical burden of management – seemed to be the most bothersome to women. For all CIN-grades, distress disappeared over six months following colposcopy, suggesting a reassuring effect of gynecological management.