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1.
Medicine (Baltimore) ; 99(20): e20199, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443342

RESUMO

INTRODUCTION: Resistance ovary syndrome (ROS) is a disease characterized by hypergonadotropic amenorrhea but with normal ovarian reserve. Currently, its pathogenesis is still unclear and the treatment methods are complex. Nevertheless, there are evident negative effects of this disease on females' physical and mental health such as gonadal dysplasia, infertility, anxiety, and depression. This article reports a case of successful ovulation induction and pregnancy with letrozole combined with HMG. This can provide clinical treatment guidelines for the disease. PATIENT CONCERNS: The patient underwent several hormone replacement cycles and ovulation induction cycles. But the dominant follicles were not extracted even after using large doses of gonadotropin. DIAGNOSIS: Resistant ovary syndrome; Primary infertility INTERVENTIONS:: Larger doses of letrozole combined with HMG were injected to stimulate ovulation and sensitize the ovaries during menstruation. This helped to examine the peripheral effects of letrozole in relation to gonadotropin. OUTCOMES: The patient displayed a dominant follicular growth and notable ovulation which resulted in a full-term pregnancy and successful delivery. CONCLUSIONS: The resistance ovary syndrome (ROS) can be treated and the findings from this case provides a possible treatment for ROS patients with infertility.


Assuntos
Inibidores da Aromatase/uso terapêutico , Letrozol/uso terapêutico , Insuficiência Ovariana Primária/tratamento farmacológico , Adulto , Inibidores da Aromatase/administração & dosagem , Quimioterapia Combinada/métodos , Feminino , Gonadotropinas/uso terapêutico , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/tratamento farmacológico , Injeções Intramusculares/métodos , Letrozol/administração & dosagem , Nascimento Vivo , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Indução da Ovulação/métodos , Gravidez , Resultado do Tratamento
2.
Georgian Med News ; (298): 27-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32141843

RESUMO

Cervical insufficiency is a common problem in obstetrical care. There are not enough studies about its development in women with infertility. The aim of the article was to determine the risk factors of the development of cervical insufficiency in women with infertility associated with anovulation. The object of the study were 308 pregnant women (110 pregnant women with cervical insufficiency and without infertility, 92 pregnant women with infertility associated with anovulation and with cervical insufficiency, 76 pregnant women with infertility associated with anovulation and without cervical insufficiency, 30 pregnant women without cervical insufficiency and infertility (controls)). We analyzed the data of obstetrical anamnesis, gynecological diseases, extragenital pathology. In fertile women with cervical insufficiency the traumatic factor of the cervix (previous labors, gynecological procedures connected with cervical dilatation) was the main in the development of this pathology. While in the women with infertility associated with anovulation the forming of cervical insufficiency was associated with hormonal reasons (hyperandrogenism (OR=3.04, 95 % CI=1.15-8.05, p=0.03), diminished ovarian reserve (OR=6.00, 95 % CI=1.97-18.24, p=0.002), controlled ovarian stimulation with gonadotropin and clomiphene citrate use (OR=3.69, 95% CI=1.93-7.04, p<0.001), use of additional reproductive technology (OR=1.95, 95 % CI=1.05-3.63, p=0.03).


Assuntos
Anovulação/complicações , Colo do Útero/anormalidades , Gonadotropinas/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Anovulação/tratamento farmacológico , Clomifeno/efeitos adversos , Clomifeno/uso terapêutico , Feminino , Gonadotropinas/efeitos adversos , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/etiologia , Gravidez , Fatores de Risco
3.
Eur J Obstet Gynecol Reprod Biol ; 243: 144-149, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31704531

RESUMO

OBJECTIVE: To study which endometrial preparation allows a better ongoing pregnancy rates (OPR) and live birth rate (LBR) after frozen-thawed embryo transfer (FET) between mild gonadotropin ovarian stimulation (OS) and artificial cycles (AC). STUDY DESIGN: Retrospective follow-up study including all FET performed in one fertility center from 2013 to 2016. In the OS group, gonadotropins were followed by r-hCG triggering. Vaginal micronized progesterone (200 mg/day) was given systematically. In the AC group, estradiol (E2) was started on Day 1. Vaginal micronized progesterone (600 mg/d) was added to E2 for 12 weeks. Data were analyzed using a multiple regression model. RESULTS: Among 1021 FETs, 35% underwent OS preparation, 65% had an AC. As expected, patients in the AC group suffered more from endometriosis (18.5% vs. 12.9%; p = .021) and polycystic ovarian syndrome (21.7% vs. 10.9%; p < .0001) than patients in the OS group. There was no difference between groups with respect to endometrial thickness, number of embryos transferred, development stage at FET, cryopreservation technique. Despite a similar clinical pregnancy rate (CPR) (24.4% vs. 20.8%; p = .189), the OPR was significantly higher in the OS than in the AC group (17.9% vs. 11%; p = .002), leading to an increased LBR (17.1% vs. 9.8%; p < .001). After adjusting for parameters usually linked to early pregnancy losses or potential bias (patient age at freezing, smoking status, PCOS, endometriosis, rank of transfer and previous miscarriages), the results remained significant. CONCLUSION: Despite a similar CPR, LBR was significantly higher with mild OS than with the AC preparation, even after adjusting for potential confounders. In light of these results, the first-line endometrial preparation could be OS instead of an AC. In an AC, a potential defect of the luteal phase may exist, treatment could be optimized to avoid pregnancy losses. A randomized controlled trial should be undertaken to assess the role of OS and ACs in FET.


Assuntos
Criopreservação , Transferência Embrionária/métodos , Nascimento Vivo/epidemiologia , Indução da Ovulação/métodos , Taxa de Gravidez , Adulto , Gonadotropina Coriônica/uso terapêutico , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Gonadotropinas/uso terapêutico , Humanos , Gravidez , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Substâncias para o Controle da Reprodução/uso terapêutico , Estudos Retrospectivos
4.
Gynecol Endocrinol ; 35(12): 1027-1036, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31392906

RESUMO

It is essential that fertility treatment is individualized based on a thorough diagnostic work-up, with treatment tailored to the patients' requirements. This individualization should be kept in mind during the main decision points that occur before and during treatment. Treatment customization must include consideration of both the woman and her partner involved in the process together, including their collective treatment goals. Once treatment goals have been agreed and diagnostic evaluations performed, personalization based on patient characteristics, together with an understanding of treatment goals and patient preferences, enables the selection of appropriate treatments, protocols, products and their dosing. Following treatment initiation, monitoring and adaptation of product and dose can then ensure optimal outcomes. Currently, it is not possible to base treatment decisions on every characteristic of the patient and personalization is based on biomarkers that have been identified as the most relevant. However, in the future, the use of artificial intelligence coupled with continuous monitoring should enable greater individualization and improve outcomes. This review considers the current state-of-the-art related to decision points during individualized treatment of female infertility, before looking at future developments that might further assist in making individualized treatment decisions, including the use of computer-assisted decision making.


Assuntos
Fármacos para a Fertilidade Feminina/uso terapêutico , Gonadotropinas/uso terapêutico , Infertilidade Feminina/terapia , Técnicas de Reprodução Assistida , Gonadotropina Coriônica/uso terapêutico , Feminino , Fertilização In Vitro/métodos , Hormônio Foliculoestimulante/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Inseminação Artificial , Hormônio Luteinizante/uso terapêutico , Indução da Ovulação/métodos , Seleção de Pacientes
5.
Acta Obstet Gynecol Scand ; 98(12): 1575-1584, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31338840

RESUMO

INTRODUCTION: Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin-stimulated in vitro fertilization compared with spontaneously conceived children: parental factors (age, health, duration of subfertility and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn being small-for-gestational-age. MATERIAL AND METHODS: We conducted a cohort study (2010-2016) of singletons (n = 155) born either after conventional gonadotropin-stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, adjusted for gestational age and sex. RESULTS: The proportion of small-for-gestational-age was 11.8% following conventional gonadotropin-stimulated in vitro fertilization and 2.9% after natural cycle in vitro fertilization (P = 0.058). The odds of small-for-gestational-age were significantly higher with supraphysiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35-15.55; P = 0.015). It remained significant after adjusting for maternal height, age and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06-13.82; P = 0.041). CONCLUSIONS: We found an associated risk of children being born small-for-gestational-age after conventional gonadotropin-stimulated in vitro fertilization compared with natural cycle in vitro fertilization. This higher risk is significantly associated with supraphysiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small-for-gestational-age and future health consequences.


Assuntos
Peso ao Nascer , Estradiol/sangue , Fertilização In Vitro/métodos , Fertilização In Vitro/estatística & dados numéricos , Gonadotropinas/uso terapêutico , Recém-Nascido Pequeno para a Idade Gestacional , Adulto , Feminino , Gonadotropinas/administração & dosagem , Humanos , Incidência , Recém-Nascido , Infertilidade Feminina/terapia , Masculino , Indução da Ovulação , Estudos Prospectivos , Fatores de Risco
6.
J Pak Med Assoc ; 69(6): 852-856, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31189294

RESUMO

OBJECTIVE: To investigate the effect of high body mass index and polycystic ovarian syndrome alone or both on the outcome of in vitro fertilisation-embryo transfer. METHODS: The retrospective study was conducted at the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China, and comprised data from August 2015 to November 2016 of infertility patients with polycystic ovarian syndrome or tubal factors who underwent agonist long-protocol in vitro fertilisation-embryo transfer. Group A comprised polycystic ovarian syndrome patients who were further divided into normal weight A1 and overweight A2. Group B had tubal patients who were further divided into normal weight B1 and overweight B2. SPSS 16 was used for data analysis. RESULTS: Of the 428 patients, 153 were in Group A and 275 in Group B. Further, Group A1 had 94(61.44%) patients and Group A2 had 59(38.56%) (p<0.01), while Group B1 had 219(81.64%) and Group B 56(18.36%) patients. The dose of gonadotropins and the duration of stimulation were significantly greater in Group A2 than Group A1(p<0.01), but there was no statistically significant difference in the tubal groups (p>0.05). Significantly more retrieved oocytes and high-quality embryos were observed in the Group A1 (p<0.01). The difference of the maturating rate, fertilisation rate, implantation rate, pregnancy rate and early abortion rate were not significant among the groups (p>0.05).. CONCLUSIONS: Polycystic ovarian syndrome with high body mass index had a negative effect on the ovarian response to gonadotropins. Pregnancy outcomes were not influenced by body mass index in tubal patients.


Assuntos
Índice de Massa Corporal , Fertilização In Vitro/estatística & dados numéricos , Síndrome do Ovário Policístico/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Feminino , Gonadotropinas/administração & dosagem , Gonadotropinas/uso terapêutico , Humanos , Recuperação de Oócitos/estatística & dados numéricos , Gravidez , Estudos Retrospectivos , Adulto Jovem
7.
Reprod Biol ; 19(2): 145-148, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31133458

RESUMO

Vascular endothelial growth factor (VEGF) is the most important angiogenic mediator in ovarian hyperstimulation syndrome OHSS. Studies proved that cabergoline administration blocks the increase in vascular permeability via dephosphorylation of VEGF receptors and hence can be used as prophylactic agent against OHSS. This study aimed at evaluating the effectiveness of early administration of cabergoline in the prevention of OHSS in high risk cases prepared for ICSI. This case series study was conducted on 126 high risk patients prepared for ICSI using the fixed antagonist protocol. High risk patients were defined as having more than 20 follicles >12 mm in diameter, and/or E2 more than 3000 pg/ml when the size of the leading follicle is more than 15 mm. When the size of the leading follicle reached 15 mm, cabergoline was administered (0.5 mg/day) for 8 days. Patients were followed up clinically, ultrasonographically and hematologically. The final E2 was 6099.5 ±â€¯2730 and the mean number of retrieved oocytes was 19.7 ±â€¯7.8. The clinical pregnancy rate was 62/126 (49.2%). There were no significant changes (p > 0.05) comparing hematological parameters, renal function tests and liver function tests between the day of HCG and the day of blastocyst transfer. The incidence of severe OHSS in this group was 1/126 (0.9%), while moderate OHSS was 12 (9.5%) and there were no cases of critical OHSS. We concluded that early administration of cabergoline is a safe and potentially more effective approach for prophylaxis against OHSS in high risk cases.


Assuntos
Cabergolina/administração & dosagem , Cabergolina/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Gonadotropinas/efeitos adversos , Síndrome de Hiperestimulação Ovariana/tratamento farmacológico , Adulto , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/uso terapêutico , Esquema de Medicação , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio Liberador de Gonadotropina/uso terapêutico , Gonadotropinas/administração & dosagem , Gonadotropinas/uso terapêutico , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Fatores de Risco , Injeções de Esperma Intracitoplásmicas , Adulto Jovem
8.
J Assist Reprod Genet ; 36(6): 1273-1280, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31073722

RESUMO

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder mostly characterized by gonadotropins release and/or action deficiencies. Both isolated (idiopathic hypogonadotropic hypogonadism) and syndromic (Kallmann) forms are identified depending on the olfactory ability. Clinical and genetic heterogeneities of CHH have been widely explored, thus improving our understanding of the disease's pathophysiology. This work aims to (1) provide a detailed clinical and hormonal description of normosmic CHH patients and (2) identify the mutation linked to the studied phenotype. PARTICIPANTS AND METHODS: We investigated three affected patients with normosmic CHH, belonging to a consanguineous Tunisian family. Patients underwent an insulin-induced hypoglycemia test. We performed whole exome sequencing to identify the causal mutation. RESULTS: At first diagnosis, a total gonadotropic deficiency was identified in all patients. The insulin-induced hypoglycemia test has also revealed a reduced cortisol secretion and complete growth hormone deficiency. At 20.8 years, one female exhibited a spontaneous recovery of the hypothalamic-pituitary-adrenal axis function, unlike her affected siblings who still depend on corticosteroid replacement therapy. Herein, we identified a novel homozygous nonstop mutation (c.1195T>C) in KISS1R gene in all affected subjects. This mutation led to the substitution of the physiologic stop codon by an arginine (p.X399R). CONCLUSIONS: Our study highlights the importance of the KISS1R signaling, in gonadotropin-releasing hormone neurons, in the control of reproductive function. Additionally, our data suggests a complex central and peripheral metabolic control of puberty, through the hypothalamic KISS1R signaling. We suggest a mutual link between the hypothalamic-pituitary-gonadal, -adrenal, and -somatotropic axes.


Assuntos
Hipogonadismo/genética , Sistema Hipotálamo-Hipofisário/metabolismo , Receptores de Kisspeptina-1/genética , Reprodução/genética , Adolescente , Corticosteroides/uso terapêutico , Adulto , Criança , Feminino , Hormônio Liberador de Gonadotropina/genética , Gonadotropinas/uso terapêutico , Humanos , Hipogonadismo/tratamento farmacológico , Hipogonadismo/patologia , Sistema Hipotálamo-Hipofisário/patologia , Masculino , Mutação , Neurônios/metabolismo , Neurônios/patologia , Linhagem , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/patologia , Sequenciamento Completo do Exoma , Adulto Jovem
9.
Clin Obstet Gynecol ; 62(2): 271-281, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30994482

RESUMO

PCOS remains one of the most intriguing endocrine disorders that physicians encounter even though it was first described over 80 years ago. Although the diagnostic criteria, nomenclature, and ideal therapeutic strategies are areas of active and ongoing debate, there is no doubt that we have made tremendous progress in improving the quality of life and reproductive outcomes of women who suffer from this wide-ranging disorder.


Assuntos
Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Antagonistas de Androgênios/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Biomarcadores/sangue , Clomifeno/uso terapêutico , Anticoncepcionais Orais Combinados/uso terapêutico , Antagonistas de Estrogênios/uso terapêutico , Feminino , Hormônio Foliculoestimulante/sangue , Gonadotropinas/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Letrozol/uso terapêutico , Hormônio Luteinizante/sangue , Metformina/uso terapêutico , Progestinas/uso terapêutico , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue
10.
Reprod Biol Endocrinol ; 17(1): 18, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728019

RESUMO

OBJECTIVE: To study the role of recombinant human LH supplementation in women with hypo-response to ovarian stimulation. METHODS: We performed a systematic review and meta-analysis of prospective clinical trials in which recombinant FSH monotherapy protocols were compared with LH-supplemented protocols in hypo-responders. A search was conducted of the Scopus, MEDLINE databases without time or language restrictions. Primary outcome was clinical pregnancy rate. RESULTS: Significantly higher clinical pregnancy rates (odds ratio: 2.03, P = 0.003), implantation rates (odds ratio: 2.62, P = 0.004) and number of oocytes retrieved (weight mean differences: 1.98, P = 0.03) were observed in hypo-responders supplemented with recombinant LH versus hypo-responders who underwent FSH monotherapy. No differences in terms of mature oocytes or miscarriage rates were found between the two groups. CONCLUSION: In conclusion, our analysis confirms that women with a hypo-response to exogenous gonadotropins might benefit from LH supplementation. However, more trials are required before a definitive conclusion can be drawn.


Assuntos
Hormônio Foliculoestimulante/uso terapêutico , Gonadotropinas/uso terapêutico , Hormônio Luteinizante/uso terapêutico , Indução da Ovulação/métodos , Proteínas Recombinantes/uso terapêutico , Ensaios Clínicos como Assunto , Implantação do Embrião/efeitos dos fármacos , Feminino , Humanos , Hormônio Luteinizante/genética , Gravidez , Taxa de Gravidez , Estudos Prospectivos
11.
Reprod Biol Endocrinol ; 17(1): 14, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30674305

RESUMO

BACKGROUND: Intrauterine insemination (IUI) is the first-line treatment for non-tubal infertility. Injectable gonadotropins are often chosen as adjunctive stimulation to promote the growth of ovarian follicles in IUI cycles. The growing follicles produce estrogen, which induces endometrial proliferation and increased endometrial stripe thickness (EST). The association between EST and pregnancy outcome in gonadotropin stimulated IUI is not well studied. The objective of this study is to determine if EST can predict pregnancy outcome in gonadotropin-stimulated IUI cycles. METHODS: A retrospective review was conducted of all exclusively gonadotropin-stimulated IUI cycles performed between 2012 and 2015 at an academic fertility clinic. Mean endometrial thickness was compared in positive versus negative cycles using Student T-test. Peak EST values were then divided into four groups of < 7 mm, 7.0-10.4 mm, 10.5-13.9 mm, and ≥ 14 mm. Multiple logistic regression analysis adjusted for potential confounders was conducted to assess the impact of peak EST on cycle outcome. RESULTS: Our sample consisted of 1065 IUI cycles representing 548 patients with a 16.9% clinical pregnancy rate and 20.5% conception rate. No significant differences in mean peak EST were observed between cycles that achieved clinical pregnancy or conception and those that did not. Division of peak EST into four groups showed a non-linear relationship between peak EST and cycle outcome, with highest rates of positive outcomes between 10.5-13.9 mm. The odds of clinical pregnancy and conception increased by 38 and 44% respectively with each subsequent peak EST category up to 10.5-13.9 mm, following which they declined. CONCLUSION: This is the largest study to date evaluating the effect of peak EST on gonadotropin-stimulated IUI cycles exclusively. The lack of significant difference in peak EST between positive and negative outcomes cycles may be due to the non-linear relationship between cycle outcomes and peak EST. Peak EST in the range of 10.5-13.9 mm was associated with significantly higher conception rates and a trend towards higher clinical pregnancy rates. This non-linearity is likely one of the reasons that EST in isolation was found to be a poor predictor of IUI outcomes, and therefore is not appropriate to be used as the sole indicator for cycle cancellation.


Assuntos
Endométrio/anatomia & histologia , Gonadotropinas/uso terapêutico , Infertilidade Feminina/terapia , Inseminação Artificial/métodos , Adulto , Feminino , Fertilização In Vitro/métodos , Humanos , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
12.
Cochrane Database Syst Rev ; 1: CD010290, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30648738

RESUMO

BACKGROUND: Ovulation induction with follicle stimulating hormone (FSH) is a second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate. OBJECTIVES: To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS), and women who do not ovulate or conceive after clomiphene citrate. SEARCH METHODS: In January 2018, we searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, the World Health Organisation clinical trials register, Clinicaltrials.gov, LILACs, and PubMed databases, and Google Scholar. We checked references of in all obtained studies. We had no language restrictions. SELECTION CRITERIA: All randomised controlled trials reporting data on clinical outcomes in women with PCOS who did not ovulate or conceive on clomiphene citrate, and undergoing ovulation induction with urinary-derived gonadotrophins, including urofollitropin (uFSH) in purified FSH (FSH-P) or highly purified FSH (FSH-HP) form, human menopausal gonadotropin (HMG) and highly purified human menopausal gonadotrophin (HP-HMG), or recombinant FSH (rFSH), or continuing clomiphene citrate. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that described co-treatment with clomiphene citrate, metformin, luteinizing hormone, or letrozole. DATA COLLECTION AND ANALYSIS: Three review authors (NW, EK, and MvW) independently selected studies for inclusion, assessed risk of bias, and extracted study data. Primary outcomes were live birth rate per woman and multiple pregnancy per woman. Secondary outcomes were clinical pregnancy, miscarriage, incidence of ovarian hyperstimulation syndrome (OHSS) per woman, total gonadotrophin dose, and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the risk ratio (RR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria. MAIN RESULTS: The review included 15 trials with 2387 women. Ten trials compared rFSH with urinary-derived gonadotrophins (three compared rFSH with human menopausal gonadotrophin, and seven compared rFSH with FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P. One trial compared FSH with continued clomiphene citrate.Recombinant FSH (rFSH) versus urinary-derived gonadotrophinsThere may be little or no difference in the birth rate between rFSH and urinary-derived gonadotrophins (RR 1.21, 95% confidence interval (CI) 0.83 to 1.78; five trials, N = 505; I² = 9%; low-quality evidence). This suggests that for the observed average live birth per woman who used urinary-derived FSH of 16%, the chance of live birth with rFSH is between 13% and 28%. There may also be little or no difference between groups in incidence of multiple pregnancy (RR 0.86, 95% CI 0.46 to 1.61; eight trials, N = 1368; I² = 0%; low-quality evidence), clinical pregnancy rate (RR 1.05, 95% CI 0.88 to 1.27; eight trials, N = 1330; I² = 0; low-quality evidence), or miscarriage rate (RR 1.20, 95% CI 0.71 to 2.04; seven trials, N = 970; I² = 0; low-quality evidence). We are uncertain whether rFSH reduces the incidence of OHSS (RR 1.48, 95% CI 0.82 to 2.65, ten trials, n=1565, I² = 0%, very low-quality evidence).Human menopausal gonadotrophin (HMG) or HP-HMG versus uFSHWhen compared to uFSH, we are uncertain whether HMG or HP-HMG improves live birth rate (RR 1.28, 95% CI 0.65 to 2.52; three trials, N = 138; I² = 0%; very low quality evidence), or reduces multiple pregnancy rate (RR 2.13, 95% CI 0.51 to 8.91; four trials, N = 161; I² = 0%; very low quality evidence). We are also uncertain whether HMG or HP-HMG improves clinical pregnancy rate (RR 1.31, 95% CI 0.66 to 2.59; three trials, N = 102; I² = 0; very low quality evidence), reduces miscarriage rate (RR 0.33, 95% CI 0.06 to 1.97; two trials, N = 98; I² = 0%; very low quality evidence), or reduces the incidence of OHSS (RR 7.07, 95% CI 0.42 to 117.81; two trials, N = 53; very low quality evidence) when compared to uFSH.Gonadotrophins versus continued clomiphene citrateGonadotrophins resulted in more live births than continued clomiphene citrate (RR 1.24, 95% CI 1.05 to 1.46; one trial, N = 661; I² = 0%; moderate-quality evidence). This suggests that for a woman with a live birth rate of 41% with continued clomiphene citrate, the live birth rate with FSH was between 43% and 60%. There is probably little or no difference in the incidence of multiple pregnancy between treatments (RR 0.89, 95% CI 0.33 to 2.44; one trial, N = 661; I² = 0%; moderate-quality evidence). Gonadotrophins resulted in more clinical pregnancies than continued clomiphene citrate (RR 1.31, 95% CI 1.13 to 1.52; one trial, N = 661; I² = 0%; moderate-quality evidence), and more miscarriages (RR 2.23, 95% CI 1.11 to 4.47; one trial, N = 661; I² = 0%; moderate-quality evidence). None of the women developed OHSS. AUTHORS' CONCLUSIONS: There may be little or no difference in live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate between urinary-derived gonadotrophins and recombinant follicle stimulating hormone in women with polycystic ovary syndrome. For human menopausal gonadotropin or highly purified human menopausal gonadotrophin versus urinary follicle stimulating hormone we are uncertain whether one or the other improves or lowers live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate. We are uncertain whether any of the interventions reduce the incidence of ovarian hyperstimulation syndrome. We suggest weighing costs and convenience in the decision to use one or the other gonadotrophin. In women with clomiphene citrate failure, gonadotrophins resulted in more live births than continued clomiphene citrate without increasing multiple pregnancies.


Assuntos
Fármacos para a Fertilidade Feminina/uso terapêutico , Gonadotropinas/uso terapêutico , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Aborto Espontâneo/epidemiologia , Coeficiente de Natalidade , Clomifeno/uso terapêutico , Resistência a Medicamentos , Feminino , Hormônio Foliculoestimulante/uso terapêutico , Humanos , Nascimento Vivo/epidemiologia , Menotropinas/uso terapêutico , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Síndrome de Hiperestimulação Ovariana/epidemiologia , Gravidez , Gravidez Múltipla/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Artigo em Inglês | MEDLINE | ID: mdl-30473207

RESUMO

Natural Cycle IVF (NC-IVF) with and without modifications is being increasingly performed. NC-IVF and conventional gonadotropin-stimulated IVF (cIVF) should not be understood as competing treatments, but as complementary treatments with different target groups and to some extent other indications. NC-IVF is particularly interesting for couples who wish to save money, wish a treatment with as few risks as possible and for women who would like to avoid selection and cryopreservation of embryos. NC-IVF therefore contributes to the concept of individualized and patient-oriented therapy. The time to pregnancy is slightly longer than with conventional IVF. NC-IVF is particularly suitable for younger women and for women with a very low ovarian reserve. In this article, the principles of NC-IVF, i.e. monofollicular IVF without gonadotropin stimulation, are described and the technical differences to cIVF, advantages and disadvantages, perinatal outcome and indications for NC-IVF are highlightened.


Assuntos
Fertilização In Vitro/métodos , Ciclo Menstrual/fisiologia , Técnicas de Reprodução Assistida , Feminino , Gonadotropinas/uso terapêutico , Humanos , Gravidez
14.
Artigo em Inglês | MEDLINE | ID: mdl-30470497

RESUMO

Medications to stimulate the ovaries may be used to induce ovulation in patients with anovulatory infertility or to hyperstimulate the ovaries in a controlled fashion in ovulatory patients as part of assisted reproductive treatments (ART). The pharmacology of all current major medications used to stimulate ovarian function is reviewed in this article, including letrozole, clomiphene citrate, gonadotropins, and pulsatile gonadotropin releasing hormone (GnRH). Novel potential compounds and adjuvant treatment approaches are also discussed, such as kisspeptin agonists and androgens.


Assuntos
Fármacos para a Fertilidade Feminina/uso terapêutico , Indução da Ovulação/métodos , Clomifeno/uso terapêutico , Feminino , Fármacos para a Fertilidade Feminina/classificação , Hormônio Liberador de Gonadotropina/uso terapêutico , Gonadotropinas/uso terapêutico , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/tratamento farmacológico , Letrozol/uso terapêutico , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Indução da Ovulação/efeitos adversos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Gravidez
15.
Genet Test Mol Biomarkers ; 22(10): 630-634, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30199281

RESUMO

TYPE OF STUDY: Retrospective analysis of embryo aneuploidy in patients undergoing in vitro fertilization (IVF) cycles. AIM: To evaluate factors that might affect the incidence of embryo aneuploidy during IVF cycles. METHODS: Three hundred twelve IVF cases were included in the present study. Preimplantation genetic testing for aneuploidy (PGT-A) was performed for all the subjects involved. Subject stratification was done based on maternal age, gonadotropin drug dosage, and IVF outcomes data. Maternal age <35 years were placed in the "Young" age group and age ≥35 years were placed in the "Advanced Maternal Age" group. Similarly, IVF drug administered <200 International units (IU) was considered "low dosage," group and ≥200 IU were considered "high dosage" group. Patients were stratified into four groups-group 1: age <35 years and administered <200 IU; group 2: age <35 years and administered ≥200 IU; group 3: age ≥35 years and administered at <200 IU; and group 4: age ≥35 years and administered ≥200 IU. PGT-A results were attained using a next-generation sequencing-based protocol. Embryo transfer was guided by transabdominal ultrasound. Statistical significance was calculated with the use of chi-square test. RESULTS: One thousand fifty blastocyst trophectoderm biopsies from 312 IVF cases were retrieved. The IVF outcome of a total of 105 normal cases resulted in 65.71% pregnancies. Stratifying for maternal age and IVF drug stimulation with PGT-A analyses we found the euploid embryo percentages equal to 37.59% in Group 1; 16.18% in Group 2; 22.44% in Group 3; and 2.59% in Group 4. Similarly the aneuploid embryo (percentage)s were 62.40% for Group 1; 83.81% for Group 2; 77.55% for Group 3; and 87.40% for Group 4. CONCLUSION: This is the first clinical study reporting that gonadotropin dosage may act as a contributing factor in increasing aneuploidy incidences for the patients undergoing IVF cycles in the UAE population. This study shows that in all patient age groups, lower drug stimulation leads to an increasing trend in embryo euploidy.


Assuntos
Blastocisto/efeitos dos fármacos , Gonadotropinas/farmacologia , Diagnóstico Pré-Implantação/métodos , Adulto , Aneuploidia , Transferência Embrionária/métodos , Feminino , Fertilização In Vitro/métodos , Testes Genéticos/métodos , Gonadotropinas/efeitos adversos , Gonadotropinas/uso terapêutico , Humanos , Idade Materna , Gravidez , Estudos Retrospectivos , Emirados Árabes Unidos
16.
Seizure ; 61: 200-202, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30199820

RESUMO

PURPOSE: Exogenous estrogens might lead to seizure worsening in women with epilepsy (WWE) by lowering the seizure threshold and inducing glucuronidation in women taking lamotrigine. Assisted reproduction techniques are increasingly used and often require estrogenic and estrogen raising hormone therapy. We aimed at reporting their possible impact on seizures in WWE. METHODS: We describe two cases of seizure exacerbation following hormone therapy for assisted reproduction in WWE. RESULTS: Patient 1: 46 years old woman, with right temporal dysplasia. At 40 years she had monthly focal seizures, possibly progressing to bilateral tonic-clonic seizures, she took levetiracetam 3000/day and she underwent gonadotropin therapy for ovarian stimulation. Estrogen blood levels showed a sudden and significant rise, up to 1019 pg/ml and she had a concomitant cluster of three tonic-clonic seizures in 24 h. Patient 2: 41 years old woman with focal epilepsy of unknown etiology. At 38 years she was taking lamotrigine 450 mg/day and had been seizure free for three years. She took estradiol valerate 4 mg for 10 days for endometrial preparation for embryo transfer and had the only seizure over six years, with the exception of auras during advanced pregnancy, related to marked decrease of lamotrigine blood levels. During adjunctive concomitant therapy with clobazam, neither patient had seizures while on hormone therapy. CONCLUSIONS: Our data suggest that hormone therapy for assisted reproduction could exacerbate seizures and should be carefully monitored in WWE, especially those taking drugs inactivated by glucuronidation. Adjunctive concomitant antiepileptic therapy should be considered.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Estrogênios/efeitos adversos , Gonadotropinas/uso terapêutico , Reprodução/efeitos dos fármacos , Sinergismo Farmacológico , Estrogênios/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Reprodução/fisiologia
17.
Reprod Biol Endocrinol ; 16(1): 89, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30217209

RESUMO

BACKGROUND: Letrozole is widely employed as ovulation induction agent in women with PCOS, but its use in mild stimulation (MS) protocols for IVF is limited. Aim of the present study was to evaluate the feasibility of a MS protocol with letrozole plus hMG in non-obese PCOS women undergoing IVF after a metformin pre-treatment. METHODS: We retrospectively evaluated the data of 125 non-obese PCOS undergoing MS with letrozole plus hMG, 150 IU as starting dose, (group 1, N = 80) compared to those undergoing a conventional IVF stimulation protocols (CS) (group 2, N = 45) prior to IVF. All patients had received metformin extended release 1200-2000 mg daily for three to six months before IVF. GnRH antagonist was administered in both groups when the leading follicles reached 14 mm. RESULTS: Both groups were comparable for age, BMI and ovarian reserve markers. Both groups showed lower than expected AFC and AMH values as a consequence of metformin pre-treatment. Letrozole-treated patients required a significantly lower amount of gonadotropins units (p < 0.0001), and showed significantly lower day 5, day 8 and hCG day E2 levels compared to patients undergoing the CS protocol (p < 0.0001, p < 0.0001 and p = 0.001 respectively). The oocyte yield, in terms of total (6, IQR 3, vs 6, IQR 4 respectively,) and MII oocytes (5, IQR 3, vs 5, IQR 3, respectively) number, did not differ among groups; the number of total (3, IQR 2, vs 3, IQR 1 respectively) and good quality embryos (2, IQR1 vs 2, IQR 1,5 respectively) obtained was comparable as well in the two groups. The number of fresh transfers was significantly higher in group 1 compared to group 2 (80% vs 60%, p = 0.016). A trend for higher cumulative clinical pregnancy rate was found in women undergoing MS compared to CS (42.5%vs 24,4%, p = 0.044), but the study was not powered to detect this difference. CONCLUSIONS: The present study suggests that the use of letrozole as adjuvant treatment to MS protocols for IVF may be an effective alternative to CS protocols for non-obese PCOS patients pre-treated with metformin, as it provides comparable IVF outcome without requiring high FSH dose, and avoiding supraphysiological estradiol levels.


Assuntos
Infertilidade Feminina/terapia , Metformina/uso terapêutico , Nitrilos/uso terapêutico , Síndrome do Ovário Policístico/complicações , Triazóis/uso terapêutico , Adulto , Feminino , Gonadotropinas/uso terapêutico , Humanos , Letrozol , Recuperação de Oócitos , Síndrome de Hiperestimulação Ovariana , Indução da Ovulação/métodos , Projetos Piloto , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas
18.
Best Pract Res Clin Endocrinol Metab ; 32(4): 355-372, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30086863

RESUMO

Management of patients with hypogonadism is dependent on the underlying cause. Whilst functional hypogonadism presenting as delayed puberty in adolescence is relatively common, permanent hypogonadism presenting in infancy or adolescence is unusual. The main differential diagnoses of delayed puberty include self-limited delayed puberty (DP), idiopathic hypogonadotropic hypogonadism (IHH) and hypergonadotropic hypogonadism. Treatment of self-limited DP involves expectant observation or short courses of low dose sex steroid supplementation. More complex and involved management is required in permanent hypogonadism to achieve both development of secondary sexual characteristics and to maximize the potential for fertility. This review will cover the options for management involving sex steroid or gonadotropin therapy, with discussion of benefits, limitations and specific considerations of the different treatment options.


Assuntos
Hipogonadismo/diagnóstico , Puberdade Tardia/diagnóstico , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Hormônios Esteroides Gonadais/uso terapêutico , Gonadotropinas/uso terapêutico , Humanos , Hipogonadismo/tratamento farmacológico , Masculino , Puberdade Tardia/tratamento farmacológico
19.
Arch Gynecol Obstet ; 298(3): 649-654, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29971557

RESUMO

PURPOSE: To evaluate whether seasonal variations can affect the outcomes of in vitro fertilization (IVF) and embryo transfer (ET). METHODS: The data of 2868 IVF-ET cycles over 5 years from patients treated for fallopian tube factors, oligospermia, and asthenospermia were collected retrospectively. The cycles were divided into four seasonal groups based on the day of ET. All cycles were performed using the gonadotropin-releasing hormone agonist and antagonist protocols. The ovarian response, embryo quality, and pregnancy outcomes were compared among groups. In addition, 4106 frozen embryo transfer (FET) cycles performed during the same period were analyzed, and the pregnancy outcomes were compared among the four seasonal groups. RESULTS: The total dose of gonadotropin in the winter group (2106.04 ± 705.57 IU) was higher than the doses in the spring and summer groups (1994.06 ± 674.95, 2009.07 ± 742.26 IU, P < 0.05). The numbers of total oocytes, matured oocytes, fertilizations, cleavages, and high-quality embryos were comparable among seasonal groups (P > 0.05). Significant differences were not observed among seasonal groups in ET or FET for the implantation rate, clinical pregnancy rate, live birth rate, and miscarriage rate (P > 0.05). CONCLUSION: Seasonal variations have little influence on the outcomes of IVF-ET and FET. IVF-ET or FET treatment can be performed during any season.


Assuntos
Implantação do Embrião , Transferência Embrionária/métodos , Fertilização In Vitro/métodos , Estações do Ano , Aborto Espontâneo/epidemiologia , Adulto , Coeficiente de Natalidade , Feminino , Gonadotropinas/uso terapêutico , Humanos , Oócitos/metabolismo , Indução da Ovulação/métodos , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Estudos Retrospectivos
20.
Fertil Steril ; 110(1): 14-18, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29980255

RESUMO

In commemoration of 40 years of in vitro fertilization (IVF), herein we describe the early evolution of the first IVF program at the Eastern Virginia Medical School in Norfolk, Virginia. The birth of the first American IVF baby was the result of the work of many investigators, both in experimental animal models and in humans, heavily relying on the experience of Robert Edwards and Patrick Steptoe in Great Britain. Although their first IVF baby was the result of the retrieval of a single oocyte in the natural cycle, duplicating their methods was not successful in Norfolk. It turns out that the achievement of the first pregnancy in the United States was associated with introducing ovarian stimulation with gonadotropins, establishing the appropriate timing for egg retrieval after hCG administration, retrieving multiple mature oocytes, determining the ideal time for in vitro insemination, and optimizing embryo culture media.


Assuntos
Fertilização In Vitro/história , Animais , Animais de Laboratório , Feminino , Fertilização In Vitro/métodos , Gonadotropinas/uso terapêutico , História do Século XX , História do Século XXI , Humanos , Recém-Nascido , Masculino , Indução da Ovulação/história , Indução da Ovulação/métodos , Gravidez , Estados Unidos
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