The effect of late-follicular phase progesterone elevation on embryo ploidy and cumulative live birth rates.

RESEARCH QUESTION: Does late-follicular phase progesterone elevation have a deleterious effect on embryo euploidy, blastocyst formation rate and cumulative live birth rates (CLBR)? DESIGN: A multicentre retrospective cross-sectional study including infertile patients aged 18-40 years who underwent ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol and preimplantation genetic testing for aneuploidies (PGT-A) followed by a freeze-all strategy and euploid embryo transfer between August 2017 and December 2019. The sample was stratified according to the progesterone concentrations on the day of trigger: normal (≤1.50 ng/ml) and high (>1.50 ng/ml). Moreover, sensitivity analyses were performed to determine whether different conclusions would have been drawn if different cut-offs had been adopted. The primary outcome was the embryo euploidy rate. Secondary outcomes were the blastocyst formation rate, the number of euploid blastocysts and CLBR. RESULTS: Overall 1495 intracytoplasmic sperm injection PGT-A cycles were analysed. Late-follicular phase progesterone elevation was associated with significantly higher late-follicular oestradiol concentrations (2847.56 ± 1091.10 versus 2240.94 ± 996.37 pg/ml, P < 0.001) and significantly more oocytes retrieved (17.67 ± 8.86 versus 12.70 ± 7.00, P < 0.001). The number of euploid embryos was significantly higher in the progesterone elevation group (2.32 ± 1.74 versus 1.86 ± 1.42, P = 0.001), whereas the blastocyst formation rate (47.1% [43.7-50.5%] versus 51.0% [49.7-52.4%]), the embryo euploidy rate (48.3% [44.9-51.7%] versus 49.1% [47.7-50.6%], the live birth rate in the first frozen embryo transfer (34.1% versus 31.1%, P = 0.427) and CLBR (38.9% versus 37.0%, P = 0.637) were not significantly different between the two groups. CONCLUSIONS: Euploidy rate and CLBR do not significantly differ among PGT-A cycles with and without late-follicular progesterone elevation in a freeze-all approach.

Physiology and pathology of ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries primed with follicle-stimulating hormone/leuteinizing hormone (LH) are subsequently exposed to human chorionic gonadotropin (hCG). The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). With the administration of hCG, the expression vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases significantly rising to a maximum coinciding with peaked VP. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. These findings suggest that the syndrome can be prevented by inducing ovulation with LH or gonadotropin-releasing hormone analogs, which prevent VEGF overexpression. Also, coadministration of a dopamine agonist inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors, the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and 44% with a placebo ( P = 0.04). Another dopamine agonist, quinagolide, was also effective in nonpregnant patients, but those pregnant did not benefit from dopamine agonist administration. In conclusion, the pathophysiological mechanisms involved in OHSS show that targeting VEGF/VEGFR2 is an effective preventive approach to treat the syndrome. Pharmaco-prevention through dopamine agonists is effective only in nonpregnant high-risk OHSS women. Embryo cryopreservation plus dopamine agonist administration might be the most appropriate way to prevent OHSS in high-risk patients.

Cigarette smoking and reproductive function.

PURPOSE OF REVIEW: To perform a systematic review of the literature on the relationship between cigarette smoking and reproductive function. Whenever possible, this review is focused on the most recently published studies (mainly the past 2 years). Nevertheless, in many instances older literature was too relevant not to be taken into account. RECENT FINDINGS: Tobacco compounds exert a deleterious effect on the process of ovarian follicle maturation. This effect is expressed by worse in-vitro fertilization parameters in cycles performed on women with smoking habits. Also, uterine receptiveness is significantly altered by the smoking habit. In men, cigarette smoking reduces sperm production, increases oxidative stress, and DNA damage. Spermatozoa from smokers have reduced fertilizing capacity, and embryos display lower implantation rates. Even in-utero exposition to tobacco constituents leads to reduced sperm count in adult life. SUMMARY: A strong body of evidence indicates that the negative effect of cigarette smoking on fertility comprises fairly every system involved in the reproductive process. Couples in reproductive age should be strongly discouraged to smoke.

The role of thrombophilia and thyroid autoimmunity in unexplained infertility, implantation failure and recurrent spontaneous abortion.

BACKGROUND: The role of thrombophilia and thyroid autoimmunity in unexplained infertility (UI), implantation failure (IF) and recurrent spontaneous abortion (RSA) is controversial and poorly understood. METHODS: From March, 2004 to January, 2007, 119 women were prospectively included: 32 oocyte donors, 31 patients with UI, 26 with IF and 30 with RSA. The IF and RSA groups presented normal preimplantation genetic screening. Protein C, protein S, antithrombin III, lupus anticoagulant, activated protein C resistance (APCR), immunoglobulin M and G anticardiolipin antibodies, homocystine, Factor V Leiden, prothrombin G20210A mutation, methylentetrahydrofolate reductase C677T mutation, thyroid-stimulating hormone (TSH), free thyroxine, anti-thyroid peroxidase (TPO) and anti-thyroglobulin (TG) antibodies were assessed. RESULTS: The prevalence of thrombophilia was high and similar among groups. In the IF group, the prevalence of APCR (15.4%), lupus anticoagulant (11.5%) and combined thrombophilia (19.2%) was higher, but not significantly different, than the other three groups. The prevalence of thyroid autoimmunity in women with IF (anti-TPO antibodies, P = 0.009; anti-TPO plus anti-TG antibodies,P = 0.04) and UI (anti-TPO, P = 0.002; anti-TG, P = 0.019; anti-TPO plus anti-TG antibodies, P = 0.005) was significantly increased in comparison to those with RSA. There was also a trend towards a higher prevalence of thyroid autoimmunity in the UI and IF groups than in the control group. TSH and free thyroxine levels all remained within a normal range. CONCLUSIONS: When embryo aneuploidy is ruled out, thrombophilia could constitute an etiologic factor in IF. Furthermore, thyroid autoimmunity is strongly related to UI and IF.

The singleton, term gestation, and live birth rate per cycle initiated: a 1-year experience in in vitro fertilization cycles with native and donated oocytes.

OBJECTIVE: To investigate the singleton, term gestation, and live birth rate per cycle initiated in our IVF program during a 1-year period. DESIGN: Retrospective study of all first IVF cycles performed in the year 2002, with or without intracytoplasmic sperm injection (ICSI), with day 2/3 embryo transfer and using native or donated oocytes. SETTING: Instituto Valenciano de Infetilidad (IVI), Valencia, Spain. PATIENT(S): Of 3,158 IVF cycles initially considered, 165 were excluded because of embryo freezing, follow-up loss, or embryo reduction. Of the remaining cycles, only 1,836 were first cycles with day 2/3 embryo transfer; of these, native oocytes were employed in 1,095 and donated oocytes in 741. INTERVENTION(S): No patient underwent any additional procedure or intervention. MAIN OUTCOME MEASURE(S): The singleton, term gestation, and live birth rate per cycle initiated was used as a primary outcome measure. Results were analyzed according to the origin of the oocytes (native vs. donated) and the woman's age (<37 and > or =37 years old). RESULT(S): The ectopic pregnancy rate was higher in the native oocyte group. The singleton, term gestation, and live birth rate per cycle initiated was similar in native and donated oocyte groups (15.3% vs. 13.4%). In the native oocyte group, patients <37 years old showed a significantly better outcome. The singleton, term gestation, and live birth rate per cycle initiated was 16.7% and 10.8% in younger and older women, respectively. CONCLUSION(S): The singleton, term gestation, and live birth rate per cycle initiated constitutes an essential parameter for determining the real possibility of a healthy baby for a specific assisted reproduction technology (ART).

First trimester biochemical screening for Down's syndrome in singleton pregnancies conceived by assisted reproduction.

BACKGROUND: Serum biochemical markers [free betahCG (fbetahCG); pregnancy-associated plasma protein-A (PAPP-A)] used in first trimester Down's syndrome screening have not been fully investigated in pregnancies achieved by assisted reproduction techniques. We present data on pregnancies conceived by all types of assisted reproduction techniques, including pregnancies following ovum donation (OD) and a large sample by ICSI. METHODS: First trimester Down's syndrome screening was performed in 1054 normal singleton pregnancies: natural conception (n = 498), ovulation induction (OS, n = 97), IVF (n = 47), ICSI (n = 222) and OD (n = 190). RESULTS: No differences in maternal levels of fbetahCG and PAPP-A, measured by the Kryptor system, appeared between naturally conceived pregnancies (n = 498) and those obtained with assisted reproduction techniques (n = 556). Several differences were apparent when comparing fbetahCG levels between different technologies but PAPP-A levels only differed between OS and IVF pregnancies (P < 0.05). In a further small study, no differences were observed using frozen embryos (n = 37), preimplantation genetic diagnosis (n = 53) or sperm from testicular biopsy (n = 21). CONCLUSIONS: Data accumulated so far suggest that first trimester biochemical markers either do not need any adjustments (e.g. in pregnancies obtained after OS and ICSI), or have very little impact (e.g. IVF pregnancies) or no impact (e.g. OD pregnancies) on the false positive rates.

[Relationship between water supply, sanitation, public health, and environment: elements for the formulation of a sanitary infrastructure planning model]. / Relações entre saneamento, saúde pública e meio ambiente: elementos para formulação de um modelo de planejamento em saneamento.

The understanding of sanitation infrastructure, public health, and environmental relations is a fundamental assumption for planning sanitation infrastructure in urban areas. This article thus suggests elements for developing a planning model for sanitation infrastructure. The authors performed a historical survey of environmental and public health issues related to the sector, an analysis of the conceptual frameworks involving public health and sanitation systems, and a systematization of the various effects that water supply and sanitation have on public health and the environment. Evaluation of these effects should guarantee the correct analysis of possible alternatives, deal with environmental and public health objectives (the main purpose of sanitation infrastructure), and provide the most reasonable indication of actions. The suggested systematization of the sanitation systems effects in each step of their implementation is an advance considering the association between the fundamental elements for formulating a planning model for sanitation infrastructure.

Relaçöes entre saneamento, saúde pública e meio ambiente: elementos para formulaçäo de um modelo de planejamento em saneamento / Relationship between water supply, sanitation, public health, and environment: elements for the formulation of a sanitary infrastructure planning model

A compreensäo das relaçöes entre saneamento, saúde pública e meio ambiente revela-se um pressuposto fundamental para o planejamento de sistemas de saneamento em centros urbanos. Nesse sentido, o presente artigo objetiva propor elementos para o desenvolvimento de um modelo de planejamento em saneamento, a partir de um levantamento histórico das questöes ambientais e de saúde incorporadas pelo setor, de uma análise dos marcos conceituais da relaçäo saúde e saneamento, e de uma sistematizaçäo dos diversos efeitos da implementaçäo de sistemas de abastecimento de água e de esgotamento sanitário no meio ambiente e na saúde pública. A avaliaçäo desses efeitos deve garantir a análise correta das possíveis alternativas, tanto do ponto de vista dos objetivos ambientais, quanto dos de saúde pública (objeto primordial do saneamento), de modo a apontar o direcionamento mais adequado das açöes. A proposta de sistematizaçäo dos efeitos das açöes de saneamento em cada fase de sua implementaçäo, realizada neste trabalho, constitui-se em um avanço, no sentido de reunir elementos fundamentais para a formulaçäo de um modelo de planejamento em saneamento