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OBJECTIVE: The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. METHODS: This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. RESULTS: There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. CONCLUSION: Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.

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SUMMARY OBJECTIVE: The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. METHODS: This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. RESULTS: There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. CONCLUSION: Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.

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OBJECTIVE: Women undergoing assisted reproductive treatment are usually concerned about the side effects caused by high doses of gonadotropin. A common inquiry of patients is concerning the weight gain as a consequence. The aim of this study was to evaluate if controlled ovarian stimulation increase the weight of women undergoing IVF treatment. Study design This retrospective cohort study included 734 women undergoing IVF treatment between January 2017 and May 2018 and had body weight measured on the day of ovarian stimulation starting (basal-weight) and on the hCG trigger day (hCG-weight). The difference of hCG-weight and basal-weight was calculated and correlated to number of oocytes retrieved and ovarian stimulation protocol. For 358 women, two international validated questionnaires to evaluate the anxiety and binge eating were applied at the end of ovarian stimulation and also associated to the body weight gain. RESULTS: The basal-weight and hCG-weight were paired compared and demonstrate a statistically significant weight gain from basal to hCG-weight of a mean of 387.7 ± 720.4 g (p < 0.001). The weight gain had a positive correlation with the number of oocytes retrieved (Pearson correlation, r = 0.181; p < 0.001) but no correlation with the ovarian stimulation protocol. Regarding the questionnaires answered by patients, neither anxiety score (Pearson: r = -0,031; p = 0,561) nor binge eating score (Pearson: r = 0,069; p = 0,199) were correlated with weight gain from basal-weight to hCG- weight. However, patients who felt eating more during the treatment had a higher weight gain (p < 0.001) independently of the number of oocytes retrieved. CONCLUSIONS: The weight gain is possibly a result from edema and is clinically irrelevant despite of the statistical significance and will probably be resolved in some days after oocytes retrieval. A small "weight gain" was observed and associated to the number of oocytes retrieved regardless of protocol and medication used in the ovarian stimulation.

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Objetivo: No nosso meio, não existem estudos que investiguem a sexualidade da mulher infértil. Sendo assim, há necessidade de uma maior compreensão dos aspectos da sexualidade dessas mulheres, assim como de possíveis disfunções sexuais nelas presentes. Material e métodos: Foram usados nesta pesquisa o Questionário do Quociente Sexual (versão feminina) e um questionário que investigava aspectos do relacionamento conjugal e sexual elaborado especialmente para esse estudo. Participaram da pesquisa 111 pacientes que buscavam por tratamentos de reprodução assistida no Projeto Beta, sem ainda terem iniciado qualquer tipo de tratamento, com idades entre 25 a 47 anos. Resultados: Os dados mostraram que 16,6% das mulheres apresentaram falta de libido, 11,9%, dificuldades de excitação sexual, 12,6%, dispareunia e 21,3%, dificuldades para atingir o orgasmo. Houve pioria da vida sexual quanto maior o tempo de infertilidade. Mulheres inférteis que já tinham filhos apresentaram significantemente melhor satisfação sexual comparadas às que não tinham. No que diz respeito ao relacionamento conjugal antes e depois da experiência de infertilidade, 60% das pacientes não relataram alterações, 26% referiram melhoria do relacionamento e 14% pioria da relação conjugal após esse problema. Conclusão: A infertilidade interfere de forma negativa na sexualidade das mulheres.

Objectives: In Brazil, there are no studies that investigate infertile women’s sexuality, so there is a need for greater understanding of aspects of their sexuality and possible dysfunctions that could be present. Materials and methods: Were used in this study a questionnaire for sexual quotient (female version) and a questionnaire investigating aspects of marital and sexual relationship prepared especially for this study. 111 patients who participated in the survey were seeking for assisted reproduction treatments in our clinic, before having initiated any kind of treatment, with ages between 25 to 47 years. Results: Collected data showed that 16.6% of the patients complained of lack of libido, 11.9%presented sexual arousal difficulties, 12.6% presented dyspareunia and 21.3% difficulties to reach an orgasm. We observed worsening of sexual life in proportion with the duration of infertility. Infertile women who already had children had significantly better sexual satisfaction compared to those that had not. Regarding marital adjustment before and afterexperiencing infertility, 60% did not refer any impairment, 26% referred enhancement and 14% referred worsening of the relationship.Conclusion: Infertility interferes in a negative way with women sexuality.

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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.

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BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability. METHODS: A randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 microg/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17-21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset < or =9 days after hCG administration) in 182 IVF patients with > or =20 but less than 30 follicles > or =10 mm. RESULTS: The incidence of moderate/severe early OHSS was 23% (12/53) in the placebo group and 12% (6/51), 13% (7/52) and 4% (1/26) in the quinagolide 50, 100 and 200 microg/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09-0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31% (8/26) with placebo to 11% (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10-0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide. CONCLUSIONS: Quinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability. ClinicalTrials.gov Identifier: NCT00329693.

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OBJECTIVE: To describe the first vaginal approach to an ectopic pregnancy after hysterectomy. DESIGN: Case report. SETTING: Private hospital. PATIENT(S): A 38-year-old woman presenting with an ectopic pregnancy 5 months after having a vaginal hysterectomy due to uterine myomatosis. INTERVENTION(S): Vaginal adnexectomy. MAIN OUTCOME MEASURE(S): Vaginal surgery as a plausible approach for this very particular situation (ectopic pregnancy in hysterectomized patient). RESULT(S): After vaginal surgery with removal of the left tube (containing a gestacional sac) and ovary, the patient fully recovered. CONCLUSION(S): Vaginal surgery can be a safe option for ectopic pregnancy resolution in noncomplicated cases.

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Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovulation induction, which may seriously affect the patient's health, with 0.1-2.0% of the patients developing severe forms of the syndrome. OHSS signs and symptoms are direct consequences of fluid shift from capillaries to the third space due to increased vascular permeability. The mechanisms of OHSS pathophysiology remain unknown but evidence obtained in animal models prove that vascular endothelial growth factor (VEGF) is directly involved and the inhibition of the VEGF system could prevent OHSS from occurring. Dopamine agonists impede the phosphorylation of the VEGF receptor 2 and reduce the incidence and severity of OHSS with a safe clinical profile. As far as is known, this is the first pathophysiological approach for treatment and prevention of OHSS.

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OBJETIVO: avaliar a eficácia da fertilização in vitro (FIV) com injeção intracitoplasmática de espermatozóide (ICSI) em ciclo natural (CN). MÉTODOS: estudo clínico retrospectivo que avaliou 70 ciclos de tratamento em 60 casais que se submeteram ao tratamento de FIV com auxílio da técnica de ICSI em CN em clínica privada de 1999 a 2003. Foi realizada monitorização ultra-sonográfica diária ou em dias alternados, e dosagem de LH urinário a partir de 16 mm de diâmetro folicular. Programada captação oocitária quando o folículo atingiu 18 mm de diâmetro e 36 horas após a administração de gonadotrofina coriônica humana (hCG - 5000UI) quando o teste de LH era negativo. A transferência embrionária foi realizada 48 a 52 horas depois do ICSI. RESULTADOS: foram realizados 70 ciclos de ICSI em 60 pacientes com as seguintes indicações: fator masculino (47,1 por cento), fator tubo-peritoneal (37,1 por cento), fatores associados (8,7 por cento) e infertilidade sem causa aparente (7,1 por cento). Do total de 70 ciclos, 18 foram cancelados (25,7 por cento de taxa cancelamento). Das 52 pacientes que se submeteram à punção ovariana, oócitos maduros foram encontrados em 77 por cento das vezes (40 ciclos). A taxa de fertilização foi de 70 por cento e as taxas de transferência embrionária por punção e por oócito maduro foram de 52 e 67,5 por cento, respectivamente. As taxas de gestação por ciclo iniciado, ciclo puncionado e transferência embrionária foram 11,4, 15,4 e 29,6 por cento, respectivamente. Das oito gestações, sete foram diagnosticadas em pacientes com idade inferior a 37 anos. A única gestação conseguida em pacientes com idade entre 37 e 43 anos evoluiu para abortamento. CONCLUSÕES: ICSI em ciclos naturais parece ser uma opção satisfatória de tratamento, com custos e índice de complicações (gestação múltipla e síndrome de hiperestímulo ovariano) reduzidos. Os resultados são melhores em pacientes mais jovens, com idade inferior a 37 anos.

PURPOSE: to evaluate the efficacy of in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) in natural cycle (NC). METHODS: retrospective clinical trial that evaluated 70 treatment cycles in 60 couples that were submitted to IVF treatment with ICSI in NC performed in private clinic from 1999 until 2003. It was performed daily ultrasound monitorization or on alternate days, and urinary LH dosage when the follicle reached 16 mm of diameter. It was scheduled egg retrieval when the follicle reached 18 mm of diameter and 36 hours after hCG administration when the LH test was negative. Embryo transfer was performed 48 to 52 hours after ICSI. RESULTS: 70 ICSI cycles in 60 patients were performed and the indications of treatment included: male factor (47.1 percent), tubal factor (37.1 percent), associated factors (8.7 percent), unknown infertility (7.1 percent). Out of 70 cycles, 18 cycles were cancelled (25.7 percent of cancellation rate). Out of 52 patients that were submitted to ovarian punction to oocyte retrieval we found mature oocytes in 77 percent of the cases (40 cycles), in four cases we collected immature oocytes and in eight cases we could not found it. We had 70 percent of fertilization rate and only one fertilized oocyte did not achieve the cleavage stage. So, the transfers rate per punction and per mature oocyte was 52 percent and 67.5 percent, respectively. We had 11.4 percent of pregnancy rate per cycle, 15.4 percent per punction and 29.6 percent per embryo transfer. CONCLUSIONS: FIV/ICSI in NC seem to be a satisfactory option of treatment, with low costs and complications (multiple gestation and Ovarian Hyperstimulation Syndrome), mainly in poor responder patients and in poor populations.

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Obesity is a rising health problem in Western societies. It has been related to increased morbidity and mortality rates due to several pathologies. In the field of gynaecology and reproduction, obesity is associated with menstrual disorders, hirsutism, infertility, miscarriage and obstetric complications. It is known to impair human reproduction through different mechanisms such as insulin resistance, hyperandrogenism and elevated leptin levels. Weight management and dietary intervention can reverse this situation and improve reproductive function. Obesity can also impair the outcome of assisted reproductive technologies. The lower probability of a healthy live birth described in obese women seems to be the result of a combination of lower implantation and pregnancy rates, higher preclinical and clinical miscarriage rates and increased complications during pregnancy for both mother and fetus. Studies performed in infertile women undergoing assisted reproduction technologies indicate that the ovary plays a leading, but not exclusive, role in the fertility prognosis of these patients. The endocrine and metabolic environment may affect oocyte quality and, therefore, embryo development, implantation and pregnancy outcome. The endometrium seems to play a subtle role in the more negative reproductive outcome of obese women, according to recent studies based on the ovum donation model.

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The recent advances in assisted reproduction have made it possible to study and interfere in almost every step of the human reproductive process except for implantation. The most complex and important step remains in great part unknown. Implantation in human has proven to be less efficient compared with other species. However, in in vitro fertilization (IVF) patients, it has been evaluated to be even poorer. This paper highlights the factors related to infertile patients and IVF treatments that can affect implantation and implantation's clinical aspects related to these treatments: implantation failure and early pregnancy loss.

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