Tubal factor, cleavage stage and more than one embryo transferred were risk factors associated with ectopic pregnancy after assisted reproductive treatment.

OBJECTIVE: Ectopic pregnancy is a well-known complication following in vitro fertilization with embryo transfer; studies have questioned, however, whether there are risk factors that could be identified before the procedure. The objective of this study was to investigate the possible risk factors involved in ectopic pregnancy following in vitro fertilization. METHODS: Retrospective case-control study performed at an assisted reproduction clinic in Brazil. To select the control group, we used a 1:4 ratio. The study included 499 patients submitted to in vitro fertilization with clinical pregnancy. We collected the data from electronic records, between 2000-2019 and divided into: Group 1, ectopic pregnancy (n=90) and Group 2, intrauterine pregnancies (n=409). RESULTS: When comparing groups, the results observed were: Tubal factor infertility (35.6% vs. 21.1%, p=.005) (OR 2.0 [1.2-3.4], p=.004); Previous miscarriage history (15.1% vs. 7.1%, p<.05) (OR 2.0 [1.02-4.29], p=.044); Number of cleavage-stage embryo transfers (69.2% vs. 54.0 p=.028) (OR 1.9 [1.08-3.33], p=.025); Two or more embryos transferred (OR 2.5 [1.12-5.70], p=.025), all associated with greater ectopic pregnancy risk. Oocyte recipient patients were excluded from this analysis, but when included a difference was found when comparing the groups (9.4% (10/106) vs. 3.0% (13/434), p=.007), (OR 3.3 [1.41-7.98] p=.005); this result should be interpreted with caution because of the sample size. CONCLUSIONS: In high-risk patients, a single blastocyst transfer seems to be a reasonable approach to decrease the ectopic pregnancy risk.

Evaluation of miR-135a/b expression in endometriosis lesions.

The pathogenesis of endometriosis is not clear; however, microRNAs (miRNAs/miRs) are involved in the pathogenesis. miRNAs are short noncoding RNAs involved in post-transcriptional regulation of gene expression by silencing the expression of target genes. The expression of miR-135a/b is associated with endometrial receptivity and implantation; the expression is also associated with the expression of certain genes, including homeobox protein Hox-A10 (HOXA-10). The present study investigated the expression of miR-135a/b in eutopic and ectopic endometrium tissues throughout the different phases of the menstrual cycle. Samples of ectopic endometriosis lesions and eutopic endometrium tissue from 23 patients who underwent laparoscopic surgery were obtained and analyzed. miRNA was extracted and the expression levels of miR-135a/b were determined by reverse transcription quantitative polymerase chain reaction assays using U6 as a housekeeping control. The expression levels of miR-135a and miR-135b in endometriosis lesions were decreased compared with the levels in endometrium tissue. However, miR-135a/b expression levels were increased in the secretory phase compared with the proliferative phase in endometriosis lesions. The increased expression of miR-135a/b during the secretory phase compared with the proliferative phase suggested that these genes serve a determinant role in the homeostasis of reproductive tissue. Therefore, the expression of genes may affect endometrial functioning, impairing embryo implantation.

Ectopic pregnancy in left ovary and contralateral uterine tube diagnosed one week apart in In Vitro Fertilization with donor eggs: Case report.

Bilateral ectopic pregnancy is a rare clinical condition with an estimated prevalence of 1/200 000 in spontaneous pregnancies. Studies have found that In Vitro Fertilization (IVF) is related to ectopic pregnancy independently, but the incidence of tubal disease in the donor egg recipient population is thought to be significantly lower than in the standard IVF population. We report the case of a patient participating in the egg-sharing program, who was diagnosed with ovarian ectopic pregnancy, treated with surgery. After one week, she was diagnosed with tubal ectopic pregnancy in the contralateral tube. The clinician should be aware that the treatment of one ectopic pregnancy does not preclude the occurrence of a second ectopic pregnancy in the same patient and should pay attention to the intra-operatory inspection of both side fallopian tubes in any ectopic pregnancy case. Routine ultrasound after ectopic pregnancy treatment may be reasonable, especially in high risk patients.

Abortamento de repetição: diagnóstico, investigação e manejo inicial / Recurrent pregnancy loss: diagnosis, investigation and initial conduct

Objetivos: O aborto de repetição acomete 1% a 2% dos casais. Tendo em vista a relevância do assunto, o presente trabalho tem como objetivo abordar o seu melhor manejo clínico. Para isso, critérios diagnósticos, métodos de investigação e tratamentos, além de uma visão geral sobre suas principais causas foram abordados. Métodos: Os artigos foram pesquisados na base de dados PubMed, em maio de 2018, utilizando os termos descritores miscarriage, recurrent; recurrent miscarriage; recurrent miscarriages; abortion, recurrent; recurrent abortion; recurrent abortions; recurrent pregnancy loss. Como critérios de inclusão, foram considerados artigos publicados nos últimos 5 anos, no período de maio de 2014 a maio de 2018, artigos que abordassem pesquisas apenas com humanos, guidelines e aqueles publicados em língua portuguesa, inglesa ou espanhola. Artigos de revisão foram excluídos da seleção. Resultados: Na pesquisa inicial, utilizando os termos descritores, foram encontrados 4492 artigos; restringindo aos últimos 5 anos, restaram 1429 artigos; desses, foram selecionados apenas aqueles com pesquisas em seres humanos, restaram 1004 artigos e desses selecionamos 962 que estão nos idiomas escolhidos. Os artigos de revisão foram excluídos da seleção. Vinte artigos foram incluídos para a elaboração desta revisão da literatura. Conclusões: Através deste artigo foi possível revisar evidências atuais referentes a diagnóstico e a manejo clínico nos casos de abortamento de repetição. Além de proporcionar conhecimento e orientação a estudantes e profissionais, o artigo levanta questões que ainda não estão bem estabelecidas na prática clínica e que ainda necessitam de maiores estudos.

Objective: The recurrent pregnancy loss affects approximately 1% to 2% of couples. Due to its importance, the present revision aims to approach the best clinical management. To do that, diagnosis criteria, research and treatments methods, as well as the general vision of the main causes, were discussed. Methods: The articles were searched in the PUBmed database, in May 2018, using keywords: miscarriage, recurrent; recurrent miscarriage; recurrent miscarriages; abortion, recurrent; recurrent abortion; recurrent abortions; recurrent pregnancy loss. As inclusion criteria, articles published in the past 5 years were chosen, from May 2014 to May 2018, articles that deal with researches in humans, guidelines and publications in portuguese, spanish or english. Revision articles were excluded. Results: In the initial search, using the terms descriptors, we found 4492 articles; restricting to the last 5 years, 1429 papers were found; selecting only those in humans, there were 1004 articles remaining and of those 962 selected in the chosen languages. Review articles were excluded from the selection. Twenty articles were selected for this review. Conclusions: Through this article it was possible to review current evidence regarding diagnosis and clinical management in recurrent pregnancy loss. In addition to provide knowledge and guidance to students and professionals, the article raises questions that are not well established in clinical practice yet and that still require further study.

Preservação da fertilidade em mulheres com câncer / Fertility preservation in women with cancer

Introdução: A fertilidade em mulheres que passaram por tratamento oncológico é um assunto de suma relevância no cenário da medicina atual. É importante que tais pacientes estejam cientes dos possíveis danos à fertilidade que o tratamento para neoplasias pode acarretar; assim como, é essencial que os médicos que lidam com elas saibam expor as opções para a preservação da fertilidade. Métodos: Os artigos foram pesquisados na base de dados PubMed em junho de 2018, utilizando os termos descritores oncologia; câncer, mulheres e fertilidade. Como critérios de inclusão, foram considerados artigos publicados nos últimos 10 anos, no período de junho de 2008 a junho de 2018, artigos que abordassem pesquisas apenas com humanos e aqueles publicados em língua portuguesa, inglesa ou espanhola. Resultados: Na pesquisa inicial, utilizando os termos descritores, foram encontrados 4173 artigos; restringindo aos últimos 10 anos, restaram 2370 artigos; desses, foram selecionados apenas aqueles com pesquisas em seres humanos, restaram 2201 artigos e desses foram selecionados 2063 que estão nos idiomas escolhidos. Elegeu-se 8 artigos para a elaboração desta revisão da literatura. Conclusões: Através deste artigo, foi possível revisar evidências atuais referentes a preservação da fertilidade em mulheres com diagnóstico de câncer. Atualmente há uma ampla variedade de abordagens para manutenção da fertilidade. Diante do desejo de gestar, as escolhas vão depender, principalmente, da idade da paciente, da reserva ovariana e da presença de parceiro.

Introduction: Fertility in women whom went through an oncologic treatment is a subject of utmost importance in the current medical scenario. It is important that these patients are aware of the possible damages to fertility due to oncologic treatments; as well as, it is essential for physicians that deal with cancer patients knowing how to disclose the options available for fertility preservation. Methods: The articles were researched in the PubMed database in June 2018, using descriptor terms as oncology; cancer; women; and fertility. As an inclusion criterion, articles published in the last 10 years were considered, from June 2008 to June 2018, articles whose research was based solely on humans and those published in Portuguese, English and Spanish. Results: In the initial research, using the descriptor terms, 4173 articles were found; restricting those to the last 10 years, 2370 were left; of these, 2201 articles whose research was solely based on humans were selected, of which 2063 are on the selected languages. Eight articles were elected for the formulation of this literature review. Conclusions: Through the elaboration of this article, it was possible to review the current relative evidence to the conservation of fertility in women with the diagnosis of cancer. Nowadays there is a broad range of approaches for the preservation of fertility. Faced on the desire to gestate, choices will vary from the age of the patient and ovarian reserve, to the presence of a male partner.

The antiapoptotic effect of galectin-3 in human endometrial cells under the regulation of estrogen and progesterone.

Galectin-3 (Gal-3), a ubiquitously expressed gene involved in many cellular processes, has been recently recognized as a factor related to endometrial receptivity. However, the precise biological function of Gal-3 in the endometrium and its regulation is still unclear. In this study, we detected the antiapoptotic role of Gal-3 in endometrial cells and the expression of Gal-3 regulated by estrogen and progesterone. We found that expression of Gal-3 increased when exposed to the apoptosis inducer staurosporine. Gal-3-silenced endometrial cells were more sensitive to the apoptosis inducer. Estradiol (E2) and progesterone (P4) up-regulated Gal-3 expression, which in turn decreased the apoptotic rate of endometrial cells. Our results strongly suggested that hormonal activation of Gal-3 by E2 and P4 is involved in inhibiting endometrial cell apoptosis, playing key roles in embryo implantation.

Global gene expression profiling of proliferative phase endometrium reveals distinct functional subdivisions.

The human endometrium follows a predictable pattern of development during the proliferative phase. Endometrial thickness increases after day 3 and then plateaus at days 9 to 10 of the menstrual cycle despite continued high serum levels of estrogen. We hypothesized that proliferative phase endometrium undergoes more than simple estrogen responsive growth, rather it is characterized by complex time-dependent functional activities reflected in differential gene expression. Nine endometrial RNA samples from healthy participants were subjected to microarray analysis and 15 samples were used for quantitative real-time polymerase chain reaction. The samples were divided into early, mid, or late proliferative phase. The early proliferative phase showed higher expression of genes including transforming growth factor ß2, chemokine (C-C motif) ligand 18 (CCL18), and metallothionein 2A. The mid-proliferative phase was characterized by higher expression of heat shock proteins and implantation-associated genes including Indian hedgehog, secreted frizzled protein 4, and progesterone receptor. In the late proliferative phase, we identified increased angiotensin II receptor, type 2 and large decrease in expression of genes related to natural killer (NK) cell function. We demonstrate a unique gene expression signature at distinct time points within the proliferative phase. The early proliferative phase is characterized by tissue remodeling, angiogenesis, and modulation of inflammation; the mid-proliferative phase is characterized not only by proliferation in response to estrogens but also marks the onset of expression of genes required for endometrial receptivity and a dampening of estrogen responsiveness. In the late proliferative phase, changes in immune function and NK cells predominate. The proliferative phase is not simply a uniform period of estrogen responsive endometrial growth that can be considered as a single experimental time point when evaluating endometrial development; rather the proliferative phase is complex with differing functions and patterns of gene expression.

A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis.

Endometriosis is found in 5-15% of women of reproductive age and is more frequent in relatives of women with the disease. Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women. We screened 150 women with endometriosis for a polymorphism in a let-7 microRNA (miRNA) binding site in the 3'-UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population. KRAS mRNA and protein expression were increased in cultured endometrial stromal cells of women with the KRAS variant. Increased KRAS protein was due to altered miRNA binding as demonstrated in reporter assays. Endometrial stromal cells from women with the KRAS variant showed increased proliferation and invasion. In a murine model, endometrial xenografts containing the KRAS variant demonstrated increased proliferation and decreased progesterone receptor levels. These findings suggest that an inherited polymorphism of a let-7 miRNA binding site in KRAS leads to abnormal endometrial growth and endometriosis. The LCS6 polymorphism is the first described genetic marker of endometriosis risk.

MicroRNA 135 regulates HOXA10 expression in endometriosis.

CONTEXT: Homeo box A10 (HOXA10) regulates endometrial receptivity and its expression is decreased in women with endometriosis. Although sex steroids regulate HOXA10, these hormones are unaltered in endometriosis. We hypothesized a role for microRNA in the regulation of HOXA10. OBJECTIVE: MicroRNA 135a and -b are small noncoding RNA with predicted targets that include HOXA10. We evaluated miR135a/b expression and HOXA10 regulation in endometrium from subjects with and without endometriosis. DESIGN: The design of the study was the measurement of miR135a/b expression by quantitative PCR and in vitro analysis of HOXA10 regulation. SETTING: The study was conducted at a university medical center. PATIENTS: Patients included 50 controls and 32 women with endometriosis. INTERVENTIONS: Study interventions included endometrial biopsies and in vitro transfection. MAIN OUTCOME MEASURES: miR135a/b and HOXA10 expression were measured in the study. RESULTS: All endometrial samples expressed miR135a and -b. miR135a expression in controls was increased during the proliferative phase, decreased at the time of ovulation, and increased during the luteal phase. Subjects with endometriosis had 3-fold higher expression of miR135a in the proliferative phase than controls. miR135b showed less variation across the menstrual cycle; however, it was significantly increased in women with endometriosis in the proliferative and secretory phases. HOXA10 expression was simultaneously repressed in the endometrium of women with endometriosis. Transfection of endometrial stromal cells with mir135a/b or miR135a/b inhibitors resulted in the altered expression of HOXA10 mRNA and protein. miR135a or -b decreased luciferase expression driven by the HOXA10 3' untranslated region containing the miR135 binding site. miR135a regulation of HOXA10 was absent in MCF-7 cells, demonstrating cell specificity. CONCLUSIONS: HOXA10 was aberrantly regulated in the endometrium of women with endometriosis by both miR135a and miR135b. Increased microRNA expression likely suppresses genes required for implantation.

Assessment of diastolic ventricular function in fetuses of diabetic mothers using tissue Doppler.

OBJECTIVE: To identify the presence of ventricular diastolic dysfunction by tissue Doppler in fetuses of diabetic mothers, with or without septal hypertrophy, in comparison to fetuses of nondiabetic mothers. METHODS: A contemporary transverse study in fetuses with a gestational age between 25 weeks to term, studying diastolic function by assessment using tissue Doppler and pulsed wave Doppler of the atrioventricular diastolic flow. The mothers of the fetuses all had previous or gestational diabetes, and were referred to the Fetal Cardiology Unit of the Institute of Cardiology in Porto Alegre, Brazil. We analysed variance with the Student-Neumann-Keuls post hoc test. An alfa of 0.05 was considered significant for statistical analysis. RESULTS: The mean myocardial velocities of the E'and A' waves at the mural mitral annulus, in fetuses of diabetic mothers with myocardial hypertrophy, were, respectively, 7.00 plus or minus 1.6 centimetres per second, and 10.24 plus or minus 3.3 centimetres per second. In the fetuses of diabetic mothers group without myocardial hypertrophy, the comparable values were 7.19 plus or minus 2.4 centimetres per second and 10.77 plus or minus 3.77 centimetres per second, respectively. In the control group, they were 4.81 plus or minus 0.85 centimetres per second and 8.01 plus or minus 2.2 centimetres per second. The difference between the velocities in fetuses of diabetic mothers and in fetal normal mothers was statistically significant (p less than 0.05). Statistically significant differences were also observed in E' and A' diastolic waves at the aortic mitral annulus, as well as for the tricuspid annulus when tissue Doppler assessment was carried out in the same sample. The mean ratio between the E and E' of mitral and tricuspid waves in the control fetuses of normal mothers was significantly higher than in fetuses of diabetic mothers. CONCLUSION: Pulsed tissue Doppler, when used in fetuses of diabetic mothers and compared with fetuses of nondiabetic mothers, shows evidence of impaired diastolic function, independently of the presence of myocardial hypertrophy.

Septo uterino, duplicação cervical e septo vaginal: relato de rara malformação mülleriana com gestação a termo / Septate uterus, cervical duplication and vaginal septum: a report of an uncommon malformation with normal term pregnancy

Apresentamos um caso de gestação espontânea em uma paciente com útero septado completo e duplicação cervical. Paciente com 34 anos, branca, nuligesta, ciclos regulares, com suspeita de septo uterino em exame ecográfico. Ao exame, apresentava septo vaginal longitudinal até a região himenal e dois colos uterinos. Solicitada ecografia pélvica tridimensional que evidenciou duplicação cervical, septo uterino do istmo à cavidade endometrial e ausência de divisão do corpo uterino, compatível com útero septado completo e duplicação cervical verdadeira. Um mês após, relatou relação sexual desprotegida e atraso menstrual. Ao exame ecográfico foi visualizado saco gestacional único na cavidade uterina direita. Apresentou gestação sem intercorrências. A cesariana ocorreu com 37 semanas, com recém-nascido do sexo feminino saudável e puerpério normal. Esse caso ilustra uma gestação espontânea, sem intercorrências, em uma rara anomalia, cujo impacto reprodutivo ainda não está totalmente elucidado.

This report describes an unusual case of spontaneous pregnancy in a patient with Müllerian anomaly. The patient was a 34-years old, white, nulligravida, with regular menstrual cycles, and suspected uterine septum observed during a routine ultrasonographic examination. The gynecological examination revealed a complete longitudinal vaginal septum and two uterine cervices. Three-dimensional pelvic ultrasonography showed cervix duplication, uterine septum from isthmus to endometrial cavity and absence of uterine body division, compatible with complete uterine septum and true dual cervices. She returned after one month and reported unprotected sexual intercourse and delayed menstrual period. She was pregnant, had a good pregnancy evolution, and delivered a healthy term baby girl, by cesarean section, at 37 weeks of pregnancy. This report describes a case of normal-term pregnancy in a patient with a rare anomaly (vaginal septum and two cervices) who became spontaneously pregnant without treatment.

Resultados de la inyección intracitoplasmática de espermatozoides en azoospermia no obstructiva: utilidad de la biopsia testicular previa / Outcome of intracytoplasmic sperm injection in non-obstructive azoospermia: usefulness of previous testicular biopsy

Objetivo: evaluar el resultado de la inyección intracitoplasmática de espermatozoides (ICSI) en parejas cuyos hombres mostraron azoospermia no obstructiva en conformidad con el hallazgo histológico del testículo. Diseño: estudio retrospectivo con análisis transversal. Materiales y métodos: han sido estudiados los resultados de laboratorio y clínicos en 59 parejas (79 ciclos) sometidas a la ICSI. Los hombres han sido divididos en 3 grupos de acuerdo con el reporte histológico obtenido en biopsia previa a la fertilización (hipoespermatogénesis, detención de la maduración espermática y aplasia de las células germinativas) y los resultados han sido comparados entre los grupos. Resultados: el hallazgo principal fue la hipoespermatogénesis (61 por ciento), seguido por la detección de la maduración espermática (22 por ciento) y la aplasia de las células germinativas (17 por ciento). Los espermatozoides estuvieron presentes en 87,7 por ciento y la tasa de fertilización (58,8 por ciento) en los casos de hipoespermatogénesis fue significativamente más grande (p<0,001) en comparación con los de detención de la maduración (50 y 40,7 por ciento) y con la aplasia de células germinativas (21,4 y 36,8 por ciento). La primera división celular tuvo una tendencia superior en los pacientes con hipoespermatogénesis (95,9 por ciento) seguido de los pacientes con detención de la maduración (87,5 por ciento) y luego los que presentan aplasia de las células germinativas (71,4 por ciento) (p = 0,001). La tasa total de embarazo clínico por ciclo iniciado y por transferencia fue de 25,3 y 37,7 por ciento, respectivamente. Conclusiones: la biopsia de testículo en hombres con azoospermia previa a la fertilización es una técnica fundamental para una orientación adecuada. Aunque los hombres con hipoespermatogénesis, es bien posible la obtención de espermatozoides, fertilización y embarazo en los pacientes cuya biopsia no ha evidenciado presencia de espermatozoides.

Falência ovariana precoce associada a deleção no braço longo do cromossomo: relato de dois casos e revisão da literatura / Premature ovarian failure with a deletion in the long arm of chromosome: report of two cases and review of the literature

Falência ovariana prematura pode ser idiopática ou estar associada a várias distúrbios auto-imunes ou genéticos, como as deleções do cromossomo X. Relatamos dois novos casos de deleções do braço longo do cromossomo X, em pacientes nuligrávidas apresentando amenorréia secundária e infertilidade. Nenhuma paciente referia história familiar de falência ovariana prematura e relatavam desenvolvimento puberal normal. A avaliação genética mostrou deleção distal no braço longo do cromossomo X, sendo os resultados 46,X,del(Xq22) e 46,X,del(Xq13q28), respectivamente. Após o diagnóstico as pacientes optaram por fertilização in vitro com óvulos doados.

Premature ovarian failure may be idiopathic or associated with several autoimmune and genetic disorders as X chromosome deletions. We report two cases of preamture ovarian failure associated with a deletion in the long arm of X chromosome. Both patients were nulligravidas presenting secondary amenorrhea and complaints of infertility, without family history of premature ovarian failure and reporting normal puberal development. Their karyotypes showed deletions of the distal long arm of all X chromosomes and were 46,X, del(Xq22) and 46,X, del(Xq13q28), respectively. After the diagnosis the patients decided to be submitted to an in vitro fertilization with egg donation.

Utero septado, duplicación del cuello y septo vaginal: informe de una rara malformación / Septate uterus, cervical duplication and vaginal septum: a report of an uncommon malformation

Objetivo: describir una rara alteración de la fusión de los canales de Müller. Diseño: presentación de caso. Reporte del caso: una paciente asiste a la consulta con un examen de ultrasonido en cuya descripción se plantea la sospecha de útero septado. El examen ginecológico reveló un septo vaginal longitudinal, que llegaba hasta la región del himen y la presencia de dos cuellos. La ecografía pélvica tridimensional mostró duplicación del cuello, útero septado que comprometía desde el istmo hasta la cavidad uterina pero sin división del cuerpo uterino, compatible con útero septado y cuello doble. Conclusión: este caso representa una rara malformación no incluida dentro de la clasificación habitual de las malformaciones Müllerianas y que no tiene explicación embriogénica, que se apoya en la teoría de la fusión unidireccional de los canales de Müller. La ecografía tridimensional es un examen simple y de bajo costo y demostró ser una buena opción para el diagnóstico definitivo de esta malformación, por lo que debe ser considerada dentro del arsenal de exámenes complementarios.

Efecto del hábito de fumar sobre los resultados de laboratorio de la fertilización in vitro / Effect of cigarette smoking on laboratorial outcome of in vitro fertilization

Objetivo: evaluar la influencia del tabaquismo femenino, activo y pasivo, sobre los resultados de la fertilización in vitro (FIV) de mujeres fumadoras. Diseño: estudio de cohorte. Materiales y métodos: ciento diecinueve (119) parejas fueron sometidas a FIV, en primer intento, cuya indicación fue el factor tubario, fueron divividos en 3 grupos: mujeres no fumadoras (n=81), mujeres fumadoras pasivas (n=15) y mujeres fumadoras verdaderas (n=23). Los resultados de laboratorio de la FIV fueron analizados en separado. Resultados: las mujeres fumadoras tuvieron un bajo índice de fertilización (40,7 por ciento) y mala calidad embrionaria (70,6 por ciento) en comparación con las no fumadoras (59,1 por ciento y 82,5 por ciento) y las fumadoras pasivas (67,4 por ciento y 87,9 por ciento) (p<0,05). No se ha encontrado difererencia en el numero de oocitos obtenidos y de embriones clivados entre los grupos. Conclusiones: los resultados indican que el éxito de la FIV puede estar afectado negativamente en las fumadoras, donde el índice de fertilización es menor y la calidad embrionaria peor.