The step-up protocol increases clinical pregnancy rates compared with the step-down in patients with unexplained infertility. A randomized controlled trial.

OBJECTIVE: Unexplained infertility is a relevant indication for controlled ovarian stimulation associated to intrauterine insemination. The "step-up" and "step-down" gonadotropin-based protocols were designed to reduce multiple pregnancy and ovarian hyperstimulation syndrome in polycystic ovary syndrome patients, but there is no related evidence in normoovulatory women undergoing intrauterine insemination. Our aim was to compare the efficacy and safety of both protocols with intrauterine insemination in unexplained infertility patients. METHODS: Randomized clinical trial including 145 women with unexplained infertility randomly following the step-up (n=73) or step-down (n=72) protocol. In the step-up group, patients started on day 3 of a spontaneous cycle administrating recombinant FSH 75IU sc/day, increasing it to 150IU if no response after 7 days. In the step-down, patients started administrating 150IU sc/day, constantly decreasing it to 75IU after 5 days. Recombinant hCG was administered when a follicle reached ≥18mm diameter. RESULTS: Clinical pregnancy rate was higher in the step-up group than in the step-down (20.5% vs . 8.3%; p =0.037). Significant differences between step-up and step-down protocols were found regarding days of rFSH administration (8.83±4.01% vs . 7.42±2.18%; p =0.001) and cancellation rate due to hyper response (8.21% vs . 25%; p =0.05). No differences were detected in miscarriage rates, multiple pregnancy rates/cycle and hyper stimulation syndrome incidence. CONCLUSIONS: The step-up protocol is longer-lasting but more effective obtaining pregnancies than the step-down in patients with unexplained infertility undergoing intrauterine insemination. This effect could be explained by lower cancellation rates due to ovarian hyper response than the step-down protocol, with no differences in ovarian hyper stimulation syndrome incidence.

The effect of short term exposure to outdoor air pollution on fertility.

BACKGROUND: There is evidence to suggest that long term exposure to air pollution could be associated with decreased levels of fertility, although there is controversy as to how short term exposure may compromise fertility in IVF patients and what windows of exposure during the IVF process patients could be most vulnerable. METHODS: This prospective cohort study aimed to evaluate the impact of acute exposure that air pollution have on reproductive outcomes in different moments of the IVF process. Women undergoing IVF living in Barcelona were recruited. Individual air pollution exposures were modelled at their home address 15 and 3 days before embryo transfer (15D and 3D, respectively), the same day of transfer (D0), and 7 days after (D7). The pollutants modelled were: PM2.5 [particulate matter (PM) ≤2.5 µm], PMcoarse (PM between 2.5 and 10µm), PM10 (PM≤10 µm), PM2.5 abs, and NO2 and NOx. Outcomes were analyzed using multi-level regression models, with adjustment for co-pollutants and confouding factors. Two sensitivity analyses were performed. First, the model was adjusted for subacute exposure (received 15 days before ET). The second analysis was based on the first transfer performed on each patient aiming to exclude patients who failed previous transfers. RESULTS: One hundred ninety-four women were recruited, contributing with data for 486 embryo transfers. Acute and subacute exposure to PMs showed a tendency in increasing miscarriage rate and reducing clinical pregnancy rate, although results were not statistically significant. The first sensitivity analysis, showed a significant risk of miscarriage for PM2.5 exposure on 3D after adjusting for subacute exposure, and an increased risk of achieving no pregnancy for PM2.5, PMcoarse and PM10 on 3D. The second sensitivity analysis showed a significant risk of miscarriage for PM2.5 exposure on 3D, and a significant risk of achieving no pregnancy for PM2.5, PMcoarse and PM10 particularly on 3D. No association was observed for nitrogen dioxides on reproductive outcomes. CONCLUSIONS: Exposure to particulate matter has a negative impact on reproductive outcomes in IVF patients. Subacute exposure seems to increase the harmful effect of the acute exposure on miscarriage and pregnancy rates. Nitrogen dioxides do not modify significantly the reproductive success.

Pelvic inflammatory disease presenting 16 months after vaginal hysterectomy: A case report and literature review.

Pelvic inflammatory disease after hysterectomy is rare and the underlying route of infection is highly heterogeneous. We report the case of a 52-year-old woman with a history of vaginal hysterectomy for uterine prolapse admitted to the emergency department with acute abdominal pain and fever. Vaginal discharge and pelvic tenderness were evident in the clinical examination. Ultrasound and computed tomography scans showed a cystic pelvic mass in contact with the vaginal cuff, suggesting the diagnosis of pelvic inflammatory disease. Laparoscopic examination revealed a bilateral tubo-ovarian abscess firmly attached and fistulized to the vaginal cuff, and after tubal removal and antibiotic coverage the patient had an optimal recovery. We performed a review of the case reports published on this subject, and concluded that pelvic inflammatory disease should not be excluded in patients with a history of hysterectomy when symptoms and findings are compatible.

Radical parametrectomy after 'cut-through' hysterectomy in low-risk early-stage cervical cancer: Time to consider this procedure obsolete.

OBJECTIVE: The goal of this study is to identify predictive factors in patients with a diagnosis of early-stage cervical cancer after simple hysterectomy in order to avoid a radical parametrectomy. METHODS: A retrospective review was performed of all patients who underwent radical parametrectomy and bilateral pelvic lymphadenectomy at MD Anderson Cancer Center and at the Instituto de Cancerologia Las Americas in Medellin, Colombia from December 1999 to September 2017. We sought to determine the outcomes in patients diagnosed with low-risk factors (squamous, adenocarcinoma or adenosquamous lesions<2cm in size, and invading<10mm) undergoing radical parametrectomy and pelvic lymphadenectomy. RESULTS: A total of 30 patients were included in the study. The median age was 40.4years (range; 26-60) and median body mass index (BMI) was 26.4kg/m2 (range; 17.7-40.0). A total 22 patients had tumors<1cm and 8 had tumors between 1 and 2cm. A total of 6 (33%) of 18 patients had evidence of lymph-vascular invasion (LVSI). No radical parametrectomy specimen had residual tumor, involvement of the parametrium, vaginal margin positivity, or lymph node metastasis. None of the patients received adjuvant therapy. After a median follow-up of 99months (range; 6-160) only one patient recurred. CONCLUSION: Radical parametrectomy may be avoided in patients with low-risk early-stage cervical cancer detected after a simple hysterectomy. Rates of residual disease (parametrial or vaginal) and the need for adjuvant treatments or recurrences are very low.

Perinatal outcomes in children born after fresh or frozen embryo transfer: a Catalan cohort study based on 14,262 newborns.

OBJECTIVE: To ascertain whether perinatal outcomes are affected by vitrification and/or controlled ovarian hyperstimulation (COH). DESIGN: Register-based cohort study. SETTING: Not applicable. PATIENT(S): Women undergoing in vitro fertilization (IVF) between 2008 and 2012 using autologous or donated eggs who had a singleton pregnancy delivered from the 24th week onward. INTERVENTION(S): Fresh embryo transfer (ET) or frozen-thawed ET in women undergoing IVF. MAIN OUTCOME MEASURE(S): Primary outcome birthweight, and secondary outcomes gestational age at delivery, small for gestational age, mode of delivery, and perinatal mortality. RESULT(S): In the autologous egg population, newborns from the fresh ET group had lower birthweight than the frozen-thawed ET group (3,152.9 ± 545.5g and 3,343.2 ± 532.3g, respectively), and this difference persisted even after adjusting for confounding factors, and the newborns had a higher risk of being small for gestational age (SGA). In contrast, among egg-donor recipients undergoing ET, the mean birthweight did not differ between the groups (3,165 ± 604.15 g and 3,143.60 ± 604.21g in the fresh and frozen-thawed ET groups, respectively); however, in the adjusted regression model birthweight was statistically significantly higher in the fresh ET group than the frozen-thawed ET group. The risk of SGA remained comparable between the fresh versus frozen-thawed ET groups. We observed no statistically significant differences in perinatal mortality between groups either in the autologous egg population or in the donor recipient group. CONCLUSION(S): Perinatal outcomes are negatively affected by COH and not affected by the vitrification process.

The impact of endometriosis on the outcome of Assisted Reproductive Technology.

BACKGROUND: Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF. METHODS: A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred. RESULTS: A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age-stratified analysis was performed, and no differences were observed in the reproductive outcomes between groups for women aged under 35 and 35 to 40. CONCLUSIONS: Reproductive outcomes among women undergoing IVF and diagnosed with endometriosis-associated infertility do not differ significantly from women without the disease. Although women with endometriosis generate fewer oocytes, fertilization rate is not impaired and the likelihood of achieving a live birth is also not affected.

Outdoor air pollution and human infertility: a systematic review.

Air pollution is a current research priority because of its adverse effects on human health, including on fertility. However, the mechanisms through which air pollution impairs fertility remain unclear. In this article, we perform a systematic review to evaluate currently available evidence on the impact of air pollution on fertility in humans. Several studies have assessed the impact of air pollutants on the general population, and have found reduced fertility rates and increased risk of miscarriage. In subfertile patients, women exposed to higher concentrations of air pollutants while undergoing IVF showed lower live birth rates and higher rates of miscarriage. After exposure to similar levels of air pollutants, comparable results have been found regardless of the mode of conception (IVF versus spontaneous conception), suggesting that infertile women are not more susceptible to the effects of pollutants than the general population. In addition, previous studies have not observed impaired embryo quality after exposure to air pollution, although evidence for this question is sparse.

Impact of air pollution on fertility: a systematic review.

Air pollution has gained considerable interest because of the multiple adverse effects reported on human health, although its impact on fertility remains unclear. A systematic search was performed to evaluate the impact of air pollutants on fertility. Controlled trials and observational studies assessing animal model and epidemiological model were included. Occupational exposure and semen quality studies were not considered. Outcomes of interest included live birth, miscarriage, clinical pregnancy, implantation, and embryo quality. Ten studies were included and divided into two groups: animal studies and human epidemiological studies including the general population as well as women undergoing in vitro fertilization and embryo transfer (IVF/ET). Results from this systematic review suggest a significant impact of air pollution on miscarriage and clinical pregnancy rates in the general population, whereas among subfertile patients certain air pollutants seem to exert a greater impact on fertility outcomes, including miscarriage and live birth rates. Besides, studies in mammals observed a clear detrimental effect on fertility outcomes associated to air pollutants at high concentration. The lack of prospective studies evaluating the effect of air pollution exposure in terms of live birth constitutes an important limitation in this review. Thus, further studies are needed to confirm these findings.

The impact of donor insemination on the risk of preeclampsia: a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to evaluate whether women who conceive with donor sperm have an increased risk of preeclampsia compared with those who use their partner's sperm. Studies that compared women who were impregnated by donor and partner sperm were included. The main outcomes assessed were preeclampsia and gestational hypertension rates. Altogether, 10,898 women (2342 pregnancies by donor sperm versus 8556 by the partner's sperm) were included from seven observational studies. Conception using donor sperm was associated with an increased risk of preeclampsia (odds ratio [OR] 1.63, 95% CI 1.36-1.95) compared with using a partner's sperm. No difference was observed in the risk of gestational hypertension (OR 0.94, 95% CI 0.43-2.03). In conclusion, pregnancies achieved by donor sperm significantly increase the risk of preeclampsia, although the underlying mechanisms remain unclear. Additional studies are required to confirm these findings.

Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of luteal phase support with vaginal progesterone in women undergoing intrauterine insemination (IUI). METHODS: Systematic review and meta-analysis. Randomized controlled trials (RCT) comparing supplementation of luteal phase with vaginal progesterone among women undergoing IUI versus a control group were included. The main outcome assessed was live birth rate. RESULTS: Five RCT met the inclusion criteria. In all 1,271 patients were included (951 IUI cycles in the progesterone group, 935 in the control group). Women treated with vaginal progesterone achieved significantly higher live birth rate (risk ratio [RR] 1.94, 95 % confidence interval [CI] 1.36 to 2.77,), and clinical pregnancy rate (RR 1.41, 95 % CI 1.14 to 1.76) as compared with controls. In the subgroup analysis per stimulation protocol, this beneficial effect of receiving progesterone was only observed in the group stimulated with gonadotropins (RR 2.28, 95 % CI 1.49 to 3.51), compared to the group stimulated with clomiphene citrate (CC) (RR 1.30, 95 % CI 0.68 to 2.50). No differences were observed in the miscarriage and multiple pregnancy rates. CONCLUSIONS: The supplementation of luteal phase with vaginal progesterone significantly increases live birth among women undergoing IUI when receiving gonadotropins for ovulation induction. Women receiving CC to induce ovulation do not seem to benefit from this treatment.

High-grade squamous intraepithelial lesion could be managed conservatively in women up to 25 years: results from a retrospective cohort study.

OBJECTIVE: The aim of this study was to compare histologic findings and clinical outcomes of women up to 25 years with a high-grade squamous intraepithelial lesion (HSIL) compared to women older than 25 years. MATERIALS AND METHODS: Sixty-three women up to 25 years and 245 women older than 25 years with HSIL, diagnosed from June 1991 to September 2008, were examined and treated following the official Spanish guidelines. Colposcopic and histologic findings and needs for treatment were recorded, and patients were followed up for a minimum of 12 months. RESULTS: A total of 308 patients were evaluated; 63.49% of women up to 25 years and 77.10% of women older than 25 years with HSIL had cervical intraepithelial neoplasia (CIN) 2+ histology (p = .04). Also, 74.60% of women up to 25 years and 99.24% of women older than 25 years underwent an excisional procedure (p < .001). No significant or clinical differences were found in the 1-year follow-up outcomes (82.54% vs 78.37% had normal results; p = ns). CONCLUSIONS: Women up to 25 years have less CIN 2+ histologic findings and less need for conization compared to older women. Our findings support the feasibility to design an adequate protocol for these younger women, which would be less aggressive and would, consequently, minimize obstetric long-term secondary effects.

Coenzyme Q10 and male infertility: a meta-analysis.

OBJECTIVE: To evaluate the effect of coenzyme Q10 treatments in male infertility, specifically in these parameters: live birth and pregnancy rates, CoQ10 seminal concentration, sperm concentration, and sperm motility. MATERIALS AND METHODS: Systematic review and meta-analysis in male infertility patients with CoQ10 oral treatments. Three trials were included: 149 males in CoQ10 group and 147 males in placebo group. RESULTS: None of the included trials provided any data regarding live births. The results of this meta-analysis show that supplementing infertile men with CoQ10 does not increase pregnancy rates. The analysis showed, among patients receiving CoQ10 treatment, a statistically significant increase in: CoQ10 seminal concentration (RR 49.55, 95 % CI 46.44 to 52.66, I(2) = 17 %), sperm concentration (RR 5.33, 95 % CI 4.18 to 6.47, I(2) = 58 %), and sperm motility (RR 4.50, 95 % CI 3.92 to 5.08, I(2) = 0 %) CONCLUSION: There is no evidence in the literature that CoQ10 increases either live birth or pregnancy rates, but there is a global improvement in sperm parameters. Adequately powered, robust trials of individual and combination antioxidant therapies are required to guide clinical practice.

Effects of transdermal testosterone in poor responders undergoing IVF: systematic review and meta-analysis.

A systematic review and meta-analysis was performed to evaluate the effect of transdermal testosterone preceding ovarian stimulation in women with poor ovarian response undergoing IVF. Studies comparing pretreatment with transdermal testosterone versus standard ovarian stimulation among poor responders were included. The main outcome assessed was live birth. Three trials were included (113 women in the testosterone group, 112 in the control group). Testosterone-treated women achieved significantly higher live birth rate (risk ratio, RR, 1.91, 95% CI 1.01 to 3.63), clinical pregnancy rate (RR 2.07, 95% CI 1.13 to 3.78) and required significantly lower doses of FSH (RR -461.96, 95% CI -611.82 to -312.09). However, differences observed in clinical pregnancy per embryo transferred were not statistically significant (RR 1.72, 95% CI 0.91 to 3.26). No differences were observed regarding number and quality of the oocytes retrieved. In conclusion, transdermal testosterone significantly increases live birth and reduces the doses of FSH required. These findings support the theoretical synergistic role of androgens and FSH on folliculogenesis. The present data should be interpreted with caution because of the small number of trials and clinical heterogeneity. The identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies. The poor response to ovarian stimulation among women undergoing IVF is of great concern in reproductive medicine. Certain modalities have been tested to improve this response to gonadotrophin stimulation, although results from some studies have shown conflicting results. Hence, a systematic review and meta-analysis was performed in order to evaluate the effect of transdermal testosterone prior to ovarian stimulation among these women with poor ovarian response. The main outcome assessed was live birth rate. In all, three trials were included, which comprehended 113 women in the testosterone group and 112 in the control group. Women that were pretreated with transdermal testosterone achieved significantly higher live birth rate and clinical pregnancy rate and required significantly lower doses of exogenous FSH as compared with controls. However, when clinical pregnancy rate was adjusted per embryo transferred differences observed were not statistically significant. No differences were observed in the number and quality of the oocytes retrieved. In conclusion, transdermal testosterone prior to ovarian stimulation significantly increases live birth and reduces the doses of FSH required among poor responders. In addition, the identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies.

¿Qué hubiera pasado si hubiésemos aplicado el Z0011 en nuestro medio? Revisión de los ganglios centinela realizados en los últimos 2 años en nuestro centro / What would happen if we applied the Z0011 study criteria? A review of the sentinel node dissections performed in our centre over the last 2 years

Objetivo: Revisar la casuística de nuestro centro para determinar en cuantas pacientes hubiéramos dejado enfermedad residual en la axila si hubiéramos aplicado los criterios del estudio Z0011. Material y métodos: Estudio retrospectivo de los ganglios centinelas (GC) realizados en carcinomas infiltrantes de nuestra Unidad de Patología Mamaria entre junio de 2008 y diciembre de 2010. Se revisaron todos los GC y las linfadenectomías axilares realizadas si 2 o menos GC eran positivos. Resultados: De 194 GC realizados, 33 resultaron positivos en 2 o menos ganglios centinelas (12,3%). La linfadenectomía axilar fue positiva en 13 casos (39,3%). Esto se produjo de forma más frecuente en las pacientes con ≤ 50 años (el 53,84 frente al 30%); en los tumores T2 en comparación con los T1 (el 53,84 frente al 30%); en los que tenían un grado histológico III comparados con los que mostraban grado I y II (el 38,46 frente al 33,33%); en aquéllos con receptores hormonales positivos en comparación con los que tenían receptores hormonales negativos (el 41,9 frente al 0%), y cuando el Ki67 era ≤ 20% en comparación con un Ki67 > a 20% (el 50 frente al 18,18%). Ninguna de estas diferencias fue estadísticamente significativa. Conclusión: Si hubiéramos aplicado los criterios del Z0011, un 39,3% de pacientes hubiera tenido enfermedad residual. Esto parece producirse con más frecuencia en pacientes de 50 o menos años, con tumoraciones de más de 2 cm, alto grado histológico, receptores hormonales positivos y Ki67 bajo. Sin embargo, el número bajo de casos de nuestra casuística no nos permite establecer unas conclusiones definitivas (AU)

Objective: To review the series of our centre in order to determine how many patients would have had residual disease in the axilla if we had applied the criteria of the Z0011 study. Material and methods: Retrospective study of sentinel lymph nodes performed in T1 and T2 breast infiltrating carcinomas in our Breast Pathology Unit between June 2008 and December 2010. We reviewed all the sentinel nodes (SN) and axillary lymph node dissections (ALND) performed when 2 or less SN were positive. Results: Of 194 sentinel nodes reviewed, 33 were positive in two nodes or less (12.3%). ALND was positive in 13 cases of 33 (39.3%). Positive ALND occurred more frequently in patients ≤ 50 years old than in > 50 years old patients (53.84% vs. 30%), in T2 compared toT1 tumours (30% vs. 53.84%), in grade III versus grade I and II tumours (38.46 vs. 33.33%), in hormone receptor-positive than in receptor-negative tumours (41.9 vs. 0%) and in Ki67 ≤ 20% compared to Ki67 > 20% tumours (50% vs. 18.18%). None of these differences were statistically significant. Conclusion: If we had applied the criteria of the Z0011 study, 39.3% of patients would have had residual disease. This seems to occur more frequently in patients 50 years or younger, with tumours larger than 2 cm, with high histological grade tumours, with positive hormone receptor and low Ki67. However, the low number of cases in our series does not allow definitive conclusions to be made (AU)