Survival in pregnancy-associated breast cancer patients compared to non-pregnant controls.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. METHODS: Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. RESULTS: Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). CONCLUSIONS: The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.

Use of steroid pre-treatments in IVF-ICSI cycles with GnRH antagonist protocol and their impact on gestational outcomes.

Different steroid pre-treatments have been used to schedule the start of the ovarian stimulation in IVF cycles. Currently, there is controversy about their effects on gestational outcomes. We designed a three-armed randomised controlled trial (RCT). Eighty-six normoresponder patients undergoing IVF treatment with antagonist GnRH protocol were allocated to three different groups. In the group 1, 34 patients received oral contraceptive pill (OCP) from the first day of the cycle to five days before starting ovarian stimulation, in the group 2, 25 patients received 2 mg/12 hours of oral E2 valerate from day 25 of the previous cycle until the day before starting stimulation, and finally, in the group 3, 27 patients did not receive any treatment. There are no statistically significant differences neither in clinical pregnancy rate (CPR) (40.9% OCP vs. 28.6% E2 vs. 53.3% no treatment group, p=.388) nor live birth rate (LBR) (31.8% OCP vs. 28.6% E2 vs. 46.7% no treatment group, p=.537) between groups in fresh embryo transfer. Likewise, no differences were found in the cumulative CPR, nor in cumulative LBR. However, there is a tendency to worst outcomes in the E2 group. In this E2 group, we observed better results with longer exposition, although no significant differences are reached (E2 mean days in the pregnant group 8.29 vs. 6.83 in the non-pregnant group, p=.08). Our study shows no significant differences in pregnancy rates between groups, but the E2 group is trending at worse gestational results. Trial registration number: Eudra-CT registration number is 2014-001809-40.Impact StatementWhat is already known on this subject? Nowadays, there is much controversy about how pregnancy rates could be affected by the selection of steroid pre-treatments used in order to schedule IVF cycles. However, these treatments are widely utilised in clinical practice.What the results of this study add? The results support the clinical findings of most of the studies previously published. No significant differences in gestational outcomes were found between the groups treated with steroid pre-treatments and the control group. Additionally, oestrogen pre-treatment seems to be related to better pregnancy outcomes when the exposition is longer. Thus, an earlier start of this treatment in the luteal phase could be the optimal approach.What the implications are of these findings for clinical practice and/or further research? This study pretends to provide clarity about the treatment guidelines of steroid pre-treatments to schedule the clinical work without impact on gestational outcomes.

Effects of progesterone variation on IVF Progesterone variation during controlled ovarian stimulation: effects on in vitro results.

The objective of this study was to investigate the impact of the progesterone variation (PV) between early progesterone and preovulatory progesterone on pregnancy rate (PR), number of oocytes, and embryo quality. Three hundred and thirty-eight cycles of in vitro fertilisation were included and progesterone was measured on 5th day of stimulation GnRH as well as on the day of induction of ovulation. Fresh embryo transfer (ET) on the second-third day after follicular puncture was made in 152/338 cycles, with positive pregnancies in 61/152 (40%). In the cycles in which ET was cancelled (186/338) higher levels of estradiol and P2 were detected, as well as greater PV and number of oocytes obtained than those made in with fresh transfer. A greater PV was not associated with a worse clinical PR but with a minor embryo quality in the group of 35-37 years old patients.Impact StatementWhat is already known on this subject? Preovulatory progesterone (P2) elevation has been linked to worse results in IVF cycles. It has also been described been reported that there is a lower pregnancy rate (PR) in patients with high progesterone in the early follicular phase (P1). In our study, we measured P1 and P2 to evaluate the possible repercussion of progesterone variation (PV) (ratio of P2 to P1) on PR, a variable that has not previously been analysed.What do the results of this study add? Negative correlation between preovulatory progesterone and embryo quality was found, according to the literature. In the present study, a negative significant correlation between PV and embryo quality was also found, however, only in the group of 35-37 years old women.What are the implications of these findings for clinical practice and/or further research? This could indicate that a rapid increase in progesterone levels after the early follicular phase is related to a lower quality of the obtained embryos, although further studies are required to achieve greater statistical significance.

Prediction of chorioamnionitis in cases of intraamniotic infection by ureaplasma urealyticum in women with very preterm premature rupture of membranes or preterm labour.

OBJECTIVES: First, to determinate the frequency of chorioamnionitis and funisitis in cases of intramniotic detection of Ureaplasma urealyticum. Second, to assess the predictive capability of some biological markers in the amniotic fluid of these women to predict histological inflammation. SUBJECTS AND METHODS: We prospectively studied 20 cases of women with premature rupture of membranes or preterm labour (PROM) or preterm labour and intraamniotic detection of Ureaplasma urealyticum. Gestational age at admission was 26.74 ± 2.53 weeks. Amniotic fluid concentrations of IL18, IL 2, IL4, IL6, IL10, IL12, TNF-alpha, IFN-g, and MMP-8 were measured by the Multiplex method. Amniotic fluid glucose and leukocyte count were also measured by standard methods. Placental detailed histological studies were performed. Student's t-test, forward stepwise conditional binary logistic regression analysis and ROC curves were used. RESULTS: Histological chorioamnionitis was present in 45% of cases (9/20) and funisitis just in 15% (3/20). Interleukins 6, 8, 12, MMP-8, and leukocyte count were significantly elevated in cases of histological inflammation, defined as choriamnionitis or chorioamniotis + funisitis (p = .007, .03, .01, .03, .03, respectively) while glucose was decreased (p = .04). Binary logistic regression for the prediction of inflammation showed a high predictive value (R2 = .66, p = .002) including in the equation only the IL6 value. CONCLUSIONS: A significant percentage of cases with intraamniotic detection of Ureaplasma urealyticum shows no pathological signs of histological inflammation. Concentration of Interleukin 6 in amniotic fluid can be useful for the diagnosis of subclinical chorioamnionitis in these cases.

Obstetric and perinatal outcome in anti-Ro/SSA-positive pregnant women: a prospective cohort study.

Anti-Ro/SS-A is one specific type of antinuclear antibodies. They are in the majority of cases associated with primary Sjögren syndrome (SS) but also in Systemic Lupus Erythematosus (SLE), rheumatoid arthritis (RA), and in healthy people. During pregnancy, they are mainly associated to congenital heart block (CHB) and neonatal lupus (NL). The aim of this study was to compare the rate of maternal and fetal complications between a series of anti-Ro/SS-A positive pregnant women prospectively followed. Forty-two anti-Ro/SSA antibodies positive pregnant women that were referred to our hospital between 2011 and 2015. Data about pregnancy follow-up and outcomes were prospectively recorded from electronic databases. Data included demographic characteristics of the patients and their diseases (type, treatments, profile of anti-Ro/SSA, and antiphospholipid antibodies), pregnancy complications (CHB, preeclampsia, preterm delivery), ultrasound examinations and conditions, and mode of delivery. Maternal age was 35.22 ± 3.42 years and most of them were either SLE (n = 16, 40%) or Sjögren syndrome (n = 15, 37.5%). The rest of them were asymptomatic carriers (n = 8; 20%), and there was only one case of rheumatoid arthritis (n = 1; 2.5%). The incidence of anti-Ro52 and anti-Ro60 positive was n = 13, 82.4% and n = 16, 100%, respectively. Anti-La/SSB antibodies were present in n = 17, 48,6% of the patients. Half of the patients were taking hydroxycloroquine (n = 18, 45%). Seven pregnancies were complicated by fetal anti-Ro-related cardiac disease (17.9%) including four cases (57.1%) of second-degree heart block, two cases of third degree heart block (28.6%) and one case (14.3%) of intense and diffuse hyperechogenicity in atrioventricular valves without heart block. Gestational age at diagnosis of these conditions was 23.2 ± 3.5 weeks. One of the 18 patients having hydroxychloroquine (5.6%) compared with the six of them in women not having this medication (6/22, 27.3%) (p = 0.10). Concerning about Doppler evaluation, the Z score of umbilical pulsatility index (PI) was significantly higher in the SLE patients (p = 0.02). There were no cases of preeclampsia. Labor was induced in 21 cases (52.5%) and cesarean section rate was 45%. Gestational age at birth was 39 (37-40) weeks, and the general prematurity rate was 20% (n = 8). Birthweight was 2985 g (2425-3185 g) and 2850 (12.25-52.50) centiles for gestational age. The rate of small for gestational age (SGA) infants was 31.3% for SLE patients (5/16), 13.3% for Sjögren syndrome (2/15), and 12.5% for asymptomatic women (1/8). The rate of neonatal acidosis (pH < 7.20) was 20% (8/34) and it was higher in the SLE cases (6/15, 40%) when delivered after 38 weeks. The main pregnancy complication associated to anti-Ro/SS-A antibodies is CHB. The prevalence of CHB in patients taking hydroxychloriquine is lower without distinguishing between high or low risk patients. Preterm delivery occurs in anti-Ro/SS-A patients at the same rate as in the general population if no complications such as CHB or intrauterine growth restriction (IUGR) occur. The SGA rate also is higher probably because of SLE not because anti-Ro/SS-A antibodies. Finally, the finding of high umbilical artery PI will allow to predict fetus at risk of adverse pregnancy outcomes. HIGHLIGHTS: •Anti-Ro/SS-A and anti-La/SS-B are clinically very relevant during pregnancy mainly because of their association to congenital heart block and neonatal lupus. •In our cohort, the prevalence of congenital heart block detected in patients taking hydroxycloroquine is much lower than in patients not taking it without distinguishing between high and low risk patients. •High umbilical artery pulsatility index in Doppler scans studies has been detected in our anti-Ro/SSA population (basely in SLE patients) demonstrated this measurement as a predictor of SGA and adverse pregnancy outcomes in general population such as cesarean section for fetal distress. The small for gestational age rate is higher probably because of SLE not because anti-Ro/SS-A •Preterm delivery happens in anti-Ro/SS-A patients at the same rate as in the general population if no complications such as congenital heart block or intrauterine growth restriction occur.

The role of surgery in advanced epithelial ovarian cancer.

Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3-17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer.