Objective The aim of this study was to determine if the individual physical characteristics of the extirpated transformation zone after large loop excision of the transformation zone (LLETZ) might predict the relative risk of adverse obstetric outcome, specifically preterm labour (PTL).Design A retrospective observational study.Setting University teaching hospital in Dublin (Coombe Women & Infants University Hospital, CWIUH).Population Women who had LLETZ treatment for cervical intraepithelial neoplasia (CIN) in the colposcopy service between 1999 and 2002, and who subsequently had a pregnancy at the CWIUH.Methods Case records and histology reports for eligible women were examined. Age, parity, smoking history, pregnancy complications and CIN grade were recorded. Exclusion criteria were age >42 years, previous treatment for CIN, previous premature labour or twin pregnancies. The Student's t-test, Mann-Whitney U-test, analysis of variants (ANOVA) and logistic regression were employed to analyse the data.Main outcome measures Gestational age at birth, PTL (i.e. <37 weeks of gestation) and miscarriage rate (<24 weeks of gestation).Results Out of 1808 women who underwent LLETZ treatment, a total of 353 women were identified who subsequently had a pregnancy at the CWIUH, with 321 being eligible for inclusion in the study. Of these, 76.3% delivered at term, 9.1% delivered at <37 weeks of gestation and 14.6% miscarried at <24 weeks of gestation. There was a three-fold increase in the risk of PTL if the excision volume exceeded 6 cm 3 (RR = 3.00; 95% CI 1.45-5.92), or when the thickness of the excised tissue was greater than 12 mm (RR = 2.98; 95% CI 1.27-7.01). The time interval between LLETZ and pregnancy did not appear to have an effect on PTL rates. We found no association between the grade of CIN and the risk of PTL.Conclusions This study reveals that the thickness and the total volume of the excised transformation zone are associated with an increased risk of PTL. Excisions thicker than 1.2 cm and larger than 6 cm 3 carry a three times greater risk for PTL.Keywords Cervical intraepithelial neoplasia, dimensions, electrosurgical excision, large loop excision of the transformation zone, loop electrosurgical excision procedure, pregnancy outcomes, preterm labour.
Flow cytometric endometrial evaluation has the ability to provide a rapid and objective analysis of lymphocyte subpopulations. The findings show significant variations in cellular proportions of immune cells across the patient categories relative to control tissue. The cell types involved suggest that a potential differential pro-inflammatory bias may exist in patients with a history of adverse reproductive outcomes. Immunological assessment in appropriate populations may provide insight into the underlying aetiology of some cases of reproductive failure.
Purpose The uterine immunophenotype is relatively poorly understood, with most studies reporting proportions/percentages. A novel technique to calculate local endometrial lymphocyte concentrations is described, and used to compare results between aetiological subgroups such as repeated implantation failure (RIF) and recurrent pregnancy loss (RPL) with male-factor controls. Methods 455 patients had an endometrial biopsy performed. Background history on initial presentation was used to subdivide the population into RIF (n = 149), RPL (n = 121), primary (n = 76) and secondary infertility (n = 80). A control group was identified comprising male factor infertility aetiology with all female investigations normal (n = 29). Endometrial Tissue was assessed using a comprehensive multi-parameter panel. Lymphocyte subpopulations were calculated using flowcount flurospheres and a mathematical correction applied to determine concentrations per milligram of tissue, based on original biopsy weight and volumetric dilutions. Results The flow cytometry technique was successful in determining population centiles for concentrations of endometrial lymphocyte subsets. Distinct differences were noted across the patient groups. Th2 concentrations were significantly higher in the controls (p = 0.0002). All RPL/infertile populations had increased concentrations of peripheral type NK's (p = 0.016) and B cells (p = 0.045). Relative to male factor controls, CD4+ and CD8+ T lymphocyte populations were increased in RPL patients, and reduced in those with a history of RIF. Th1 concentrations were elevated in the adverse outcome groups (p = 0.032). Concentration centiles alone do not appear to accurately predict outcome with subsequent treatment. Conclusions Endometrial biopsy analysis by flow cytometry can provide detailed analysis of constituent lymphocyte subsets by concentration as well as proportion. This novel approach provides additional independent data to further assess the significance of endometrial changes in the setting of reproductive failure.
Predicting reproductive outcomes with IVF has great utility both for patients and providers. The former have the opportunity to build realistic expectations, and the latter are better able to counsel according to measured clinical parameters. A better understanding of follicular dynamics and ovarian response to gonadotropin stimulation could optimize IVF treatments going forward.
We recommend that each ART centre defines their "own" normograms for accurate advice for and treatment of their patients. External laboratory-defined "normal" and "abnormal" AMH levels should be filtered and adapted to the reality of each population. These findings need to be considered when counselling patients and planning treatments as age-specific population normograms can provide a tailored approach.
Before commencing chemotherapy or radiotherapy, patients in the oncology group at the margins of reproductive age had a diminished ovarian reserve compared with the control group. This should be considered when planning optimal doses of follicular stimulating hormone as part of controlled ovarian-stimulation regimes performed for embryo or oocyte cryopreservation prior to chemotherapy or radiotherapy.
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