Joaquim Nunes

Characterizing partial AZFc deletions of the Y chromosome with amplicon-specific sequence markers

BackgroundThe AZFc region of the human Y chromosome is a highly recombinogenic locus containing multi-copy male fertility genes located in repeated DNA blocks (amplicons). These AZFc gene families exhibit slight sequence variations between copies which are considered to have functional relevance. Yet, partial AZFc deletions yield phenotypes ranging from normospermia to azoospermia, thwarting definite conclusions on their real impact on fertility.ResultsThe amplicon content of partial AZFc deletion products was characterized with novel amplicon-specific sequence markers. Data indicate that partial AZFc deletions are a male infertility risk [odds ratio: 5.6 (95% CI: 1.6–30.1)] and although high diversity of partial deletion products and sequence conversion profiles were recorded, the AZFc marker profiles detected in fertile men were also observed in infertile men. Additionally, the assessment of rearrangement recurrence by Y-lineage analysis indicated that while partial AZFc deletions occurred in highly diverse samples, haplotype diversity was minimal in fertile men sharing identical marker profiles.ConclusionAlthough partial AZFc deletion products are highly heterogeneous in terms of amplicon content, this plasticity is not sufficient to account for the observed phenotypical variance. The lack of causative association between the deletion of specific gene copies and infertility suggests that AZFc gene content might be part of a multifactorial network, with Y-lineage evolution emerging as a possible phenotype modulator.

Clinical Characteristics and Outcome of Treatment of Brazilian Women with Breast Cancer Treated at Public and Private Institutions – The AMAZONE Project of the Brazilian Breast Cancer Study Group (GBECAM).

Introduction: With close to 50,000 new cases/year, breast cancer is the most common cancer among Brazilian women. There are few data regarding the clinical presentation, treatment and outcome of this population.Methods: The Brazilian Breast Cancer Study Group (GBECAM) collected data from 28 cancer centers distributed throughout the country on 1-) clinical characteristics, 2-) type of treatment received and 3-) survival curves of 4,912 Brazilian women presenting with breast cancer and treated at public (Pu), and private (Pr) institutions in the years 2001(N=2,198) and 2006 (N=2,714).Results:1-) Mean age at diagnosis was 59.3 (median=58), with 25.4% below age 50. Stage 0 was seen in 2.8%, Stage I in 20.2%, Stage II in 46.8%, Stage III in 24.6% and Stage IV in 5.5%. Clinical Stage III+IV was seen in 36.9% of pts in Pu, and only 16.2% in Pr institutions. Hormone Receptors were positive in 69.9% of pts; HER2 was overexpressed/amplified in 20.3%; 19.1% of the cases were triple-negative. 2-) Neoadjuvant chemotherapy (CT) was done in 26.5% of cases in Pu and only 11% of Pr pts. Breast-conserving surgery was performed in 40.9% of Pu and 51.7% of Pr pts. Sentinel node biopsy was done in 15.9% of Pu and 25.9% of Pr pts. Adjuvant therapy was done in 88.2% of the cases. Adjuvant CMF was done in 31.4% of Pu and 15.8% of Pr pts; anthracycline plus taxane was used in 9.2% of Pu and 23.5% of Pr pts. In the cohort of 2006, adjuvant trastuzumab was given to 56.2% of Pr but only 6.6% of Pu pts. Adjuvant hormonal therapy consisted of tamoxifen (TAM) in 86.6%, aromatase inhibitors (AI) in 6.3% and sequential Tam/AI in 6.6% of pts. Adjuvant radiotherapy was given to 76% of the cases. 3-) Survival was studied for all patients of the 2001 cohort. Disease-free survival (DFS) at 5 years was 78% for Pr vs 72% for Pu institutions. Overal survival (OS) at 5 years was 97% in Pr vs 88% in Pu institutions. When analyzed by stage, there was no apparent difference when pts with stage I or II were treated in Pr or Pu institutions. In stage III, however, DFS was 61% in Pr vs 47% in Pu institutions. OS in Stage III disease was 95% for Pr vs 65% in Pu institutions.Conclusions: Our data suggest that pts with breast cancer in Brazil present with more advanced stages in Pu institutions. These pts are more likely to receive neoadjuvant CT and undergo total mastectomy. These pts receive more CMF and less anthracycline/taxane combinations as adjuvant CT. Patients with Stage III disease treated in Pu institutions have inferior DFS and OS compared to similar pts treated in Pr institutions. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3082.

Influence of body mass index in anti-Müllerian hormone levels in 951 non-polycystic ovarian syndrome women followed at a reproductive medicine unit

PurposeAnti-Müllerian hormone (AMH) is a useful marker of ovarian reserve. Obesity/overweight are increasing and may affect the reproductive health. Previous studies regarding the effect of body mass index (BMI) on AMH levels are discordant. Our main goal was to evaluate the influence of BMI on AMH levels in women without polycystic ovarian syndrome.MethodsRevision of medical records of 951 women who performed AMH determinations as part of their fertility workup, between 2011 and 2016.ResultsMedian AMH concentration was 1.75 [interquartile range (IQR) 2] ng/mL (12.9 pmol/mL) and median age at AMH determination was 35 (IQR 6) years. These women evidenced a median BMI of 23 (IQR 5) kg/m2. Caucasian women were more represented [889(89.3%)]. Smoking habits (present/past) were present in 359(36.1%), and 147(14.8%) harboured a history of ovarian surgery. On univariable analysis AMH was not correlated with BMI (r = 0.048/p = 0.135); the only factors influencing AMH were age (p < 0.001), ethnicity (p = 0.004), and previous ovarian surgery (p < 0.001). On multivariable analysis, age was the only variable significantly associated with AMH, evidencing a reduction of 6.2% for each additional year (p < 0.0001). Furthermore, we verified a trend suggesting an AMH reduction of 22% (p = 0.08) in black patients comparing with the caucasian ones, when controlling for the other variables.ConclusionWe report one of the largest series evaluating the influence of BMI on AMH levels and, consequently, on ovarian reserve. BMI does not seem to affect AMH levels. The reported concerns on infertility in overweight and obese women may be related to follicular development/oocyte maturation or endometrial disorders, rather than decreased ovarian reserve.

Short and Long-Term Efficacy of Laparoscopic Ovarian Diathermy in Women with Polycystic Ovary Syndrome

INTRODUCTION Polycystic ovary syndrome is the most frequent cause of anovulatory infertility and management involves a multistep approach. Laparoscopic ovarian diathermy is accepted as a second-line treatment of patients who failed to respond to clomiphene citrate. The aims of this study were to determine the efficacy of this technique at short and long-term and to perform an analysis of predictive factors of spontaneous pregnancy. MATERIAL AND METHODS This retrospective study involved 76 women who underwent laparoscopic ovarian diathermy between 2004 and 2013 in a university hospital. Main outcomes were cycle regularity and pregnancy. Short-term outcomes recorded during followup in our centre were reviewed and long-term outcomes were evaluated by a telephone interview to all women whose surgery was undertaken more than three years ago. Clinical and biochemical data were analysed as predictive factors of spontaneous conceptionin patients without other infertility factors. RESULTS Menstrual cycle regularity was initially achieved in 53 (70%) women and in the long-term follow-up subgroup, 52% (12/23) had regular periods. In general, 53 (70%) women conceived and 77 pregnancies were achieved, 60% of which were spontaneous. The only prognostic factor found to be significantly associated with spontaneous conception was a shorter duration of infertility (< 3 years) (p < 0.05). DISCUSSION Laparoscopic ovarian diathermy showed pregnancy rates comparable to other ovulation induction treatments with the advantage of having a long lasting beneficial effect in menstrual regularity and fertility. CONCLUSION Laparoscopic ovarian diathermy is a safe and effective treatment option for anovulatory infertility in women with polycystic ovary syndrome.