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1.
BMC Pregnancy Childbirth ; 21(1): 33, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413226

RESUMO

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) has been reported to play a key role in placental development during normal pregnancy. However, the question of whether endometrial IDO expression affects in vitro fertilization (IVF) pregnancy outcomes remains unclear. The current study was undertaken to investigate whether there was any association between endometrial IDO immunohistochemical staining and IVF treatment outcome. METHODS: This retrospective study was designed to compare pregnancy outcomes among women with different endometrial IDO expression levels under their first IVF treatment. A total of 140 women undergoing their IVF treatment were selected from January 2017 to December 2017. Endometrial samples were collected during mid-luteal phase before IVF cycle. The endometrial IDO expression levels were analyzed by immunohistochemistry, and compared between women who were pregnant or not. A logistic regression analysis was performed to determine the impact of endometrial IDO staining on live birth. RESULTS: No significant differences in the endometrial IDO immunohistochemical staining were found between women who had clinical pregnancy and those who failed (P>0.05). However, the endometrial IDO staining was significantly higher among women who had live birth compared with those who had no live birth (P=0.031). Additionally, after adjusting for differences in maternal age, BMI and duration of gonadotropin stimulation, women with higher IDO expression level had an increased live birth rate (adjusted odds ratio [aOR] 2.863, 95% confidence interval [CI] 1.180-6.947). CONCLUSIONS: Higher endometrial IDO expression level during mid-luteal phase is associated with an increased live birth rate in women undergoing their first IVF treatment.


Assuntos
Coeficiente de Natalidade , Endométrio/enzimologia , Fertilização In Vitro , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Adulto , Índice de Massa Corporal , Transferência Embrionária/métodos , Feminino , Gonadotropinas/uso terapêutico , Humanos , Imuno-Histoquímica , Nascido Vivo , Fase Luteal/metabolismo , Idade Materna , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Análise de Regressão , Estudos Retrospectivos
2.
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 , Nascido Vivo , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Indução da Ovulação/métodos , Gravidez , Resultado do Tratamento
3.
J Ovarian Res ; 13(1): 36, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32247312

RESUMO

BACKGROUND: Women with irregular menstruation should be considered to benefit from the ovarian stimulation. However, most literature did not separate ovulatory disorders from normal menstrual cycles. Our purpose was to assess the superiority of ovarian mild stimulation compared with the natural cycle in IUI for subfertile couples when the women with regular menstruation. METHODS: A retrospective study in a single medical center in which 2413 couples with 3573 IUI cycles were studied from 2013 to 2018. The results of IUI in natural cycles versus low-dose HMG induced cycles were analyzed. RESULTS: For young women (age < 35 years) with normal menstrual cycle, HMG induced ovulation combined with IUI can improve clinical pregnancy outcome (13.55% in two follicular induced cycles vs. 7.23% in natural cycles, p < 0.01); even if only one follicle was induced, the clinical pregnancy rate was increased to 10.32% (p < 0.01). When two growth follicles were induced in HMG cycles, a remarkable improvement of the live birthrate (10.28% vs. 5.91% in natural cycles, p < 0.05) was noted. Simultaneously, twin pregnancy rates were increased to 20.69% (p < 0.01). Twin pregnancies showed significantly increased risk of both ectopic pregnancy and preterm birth (p = 0.00 for both). For advanced women (age ≥ 35 years) with regular menstrual cycle, ovulation induction didn't improve clinical pregnancy and live birthrates, while age was the only relevant factor. CONCLUSIONS: Combining HMG induced ovulation and IUI can improve pregnancy outcome in young women with normal menstrual cycles. 1-2 follicles with diameter ≥ 14 mm served as the purpose of ovulation induction. Further, both twin and ectopic pregnancy rate in HMG cycles with two growth follicles were significantly higher than those in natural cycles were. Therefore, doctors must evaluate the risk before making choices and inform the patients to achieve the best results. For advanced women with normal menstrual cycles, natural IUI cycles were optional.


Assuntos
Gonadotropinas/uso terapêutico , Infertilidade/tratamento farmacológico , Inseminação Artificial , Indução da Ovulação/métodos , Adulto , Feminino , Humanos , Masculino , Menopausa , Ovulação , Gravidez , Resultado da Gravidez
4.
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
5.
Hum Reprod Update ; 26(2): 247-263, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32045470

RESUMO

BACKGROUND: Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. OBJECTIVE AND RATIONALE: The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. SEARCH METHODS: Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217). OUTCOMES: Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). WIDER IMPLICATIONS: For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.


Assuntos
Resistência a Medicamentos , Fertilização In Vitro/métodos , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Clomifeno/uso terapêutico , Terapia Combinada/métodos , Terapia Combinada/estatística & dados numéricos , Ensaios Clínicos Controlados como Assunto/estatística & dados numéricos , Feminino , Fertilização In Vitro/estatística & dados numéricos , Hormônio Liberador de Gonadotropina/uso terapêutico , Gonadotropinas/uso terapêutico , Humanos , Letrozol/uso terapêutico , Metanálise em Rede , Indução da Ovulação/efeitos adversos , Indução da Ovulação/estatística & dados numéricos , Gravidez , Resultado da Gravidez/epidemiologia , Taxa de Gravidez
6.
Fertil Steril ; 113(2): 305-322, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32106976

RESUMO

OBJECTIVE: To provide evidence-based recommendations to practicing physicians and others regarding the effectiveness and safety of therapies for unexplained infertility. METHODS: ASRM conducted a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1968 through 2019. The ASRM Practice Committee and a task force of experts used available evidence and informal consensus to develop evidence-based guideline recommendations. MAIN OUTCOME MEASURE(S): Outcomes of interest included: live-birth rate, clinical pregnancy rate, implantation rate, fertilization rate, multiple pregnancy rate, dose of treatment, rate of ovarian hyperstimulation, abortion rate, and ectopic pregnancy rate. RESULT(S): The literature search identified 88 relevant studies to inform the evidence base for this guideline. RECOMMENDATION(S): Evidence-based recommendations were developed for the following treatments for couples with unexplained infertility: natural cycle with intrauterine insemination (IUI); clomiphene citrate with intercourse; aromatase inhibitors with intercourse; gonadotropins with intercourse; clomiphene citrate with IUI; aromatase inhibitors with IUI; combination of clomiphene citrate or letrozole and gonadotropins (low dose and conventional dose) with IUI; low-dose gonadotropins with IUI; conventional-dose gonadotropins with IUI; timing of IUI; and in vitro fertilization and treatment paradigms. CONCLUSION(S): The treatment of unexplained infertility is by necessity empiric. For most couples, the best initial therapy is a course (typically 3 or 4 cycles) of ovarian stimulation with oral medications and intrauterine insemination (OS-IUI) followed by in vitro fertilization for those unsuccessful with OS-IUI treatments.


Assuntos
Infertilidade Feminina/terapia , Inseminação Artificial/métodos , Inibidores da Aromatase/uso terapêutico , Clomifeno/uso terapêutico , Prática Clínica Baseada em Evidências , Feminino , Fertilização In Vitro , Gonadotropinas/uso terapêutico , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Aust N Z J Obstet Gynaecol ; 60(2): 271-277, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31994179

RESUMO

BACKGROUND: The use of gonadotrophins as a first-line treatment for anovulatory infertility has been limited by a perception of a risk of multi-fetal gestation and ovarian hyperstimulation syndrome (OHSS). However, it has recently been recognised as an acceptable first-line treatment if appropriate monitoring is performed. AIMS: To determine the cumulative live birth rate, incidence of multiple gestation, cycle cancellation rate and incidence of OHSS for therapy-naïve anovulatory women undergoing ovulation induction with gonadotrophins. MATERIALS AND METHODS: A prospective observational study of 258 patients undergoing ovulation induction with a 'low-dose step-up' protocol was performed over a three-year period across two fertility centres (40% of patients were currently or recently prescribed metformin). RESULTS: Twenty-six percent of patients required concurrent use of luteinising hormone. The cumulative pregnancy and live birth rates were 22.5% and 18.2%, 40.3% and 34.5%, 47.7% and 41.1% after completion of the first, second and third cycles of stimulation, respectively, with a median duration of stimulation of 15 days. No patients developed OHSS and 10.5% of cycles were cancelled due to an excessive or no follicular response. The multiple pregnancy rate was 2%. The cumulative pregnancy rate was reduced for women over 35 years of age (23.8 vs 55.3%, P = 0.006) and for women with a body mass index greater than 25 kg/m2 (40.6 vs 56.7%, P = 0.027). CONCLUSIONS: This study demonstrated that ovulation induction with gonadotrophin therapy, in the context of appropriate monitoring, is a safe and effective treatment for young therapy-naïve patients with anovulatory infertility.


Assuntos
Anovulação/tratamento farmacológico , Coeficiente de Natalidade , Gonadotropinas/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Síndrome de Hiperestimulação Ovariana , Indução da Ovulação , Adulto , Feminino , Fármacos para a Fertilidade Feminina/uso terapêutico , Humanos , Gravidez , Gravidez Múltipla/estatística & dados numéricos , Estudos Prospectivos
8.
Hum Reprod Update ; 26(1): 1-15, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31803930

RESUMO

BACKGROUND: IUI for unexplained infertility can be performed in a natural cycle or in combination with ovarian stimulation. A disadvantage of ovarian stimulation is an increased risk of multiple pregnancies with its inherent maternal and neonatal complication risks. Stimulation agents for ovarian stimulation are clomiphene citrate (CC), Letrozole or gonadotrophins. Although studies have compared two or three of these drugs to each other in IUI, they have never been compared to one another in one analysis. OBJECTIVE AND RATIONALE: The objective of this network meta-analysis was to compare the effectiveness and safety of IUI with CC, Letrozole or gonadotrophins with each other and with natural cycle IUI. SEARCH METHODS: We searched PubMed, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL and the Clinical Trial Registration Database indexed up to 16 August 2018. We included randomized controlled trials that compared a stimulation regimen with CC, Letrozole or gonadotrophins to each other or to natural cycle IUI among couples with unexplained infertility. We performed the network meta-analysis within a multivariate random effects model. OUTCOMES: We identified 26 studies reporting on 5316 women. The relative risk (RR) for live birth/ongoing pregnancy rates comparing IUI with CC to natural cycle IUI was 1.05 (95% CI 0.63-1.77, low quality of evidence), while comparing IUI with Letrozole to natural cycle IUI was 1.15 (95% CI 0.63-2.08, low quality of evidence) and comparing IUI with gonadotrophins to natural cycle IUI was 1.46 (95% CI 0.92-2.30, low quality of evidence). The RR for live birth/ongoing pregnancy rates comparing gonadotrophins to CC was 1.39 (95% CI 1.09-1.76, moderate quality of evidence), comparing Letrozole to CC was 1.09 (95% CI 0.76-1.57, moderate quality of evidence) and comparing Letrozole to gonadotrophins was 0.79 (95% CI 0.54-1.15, moderate quality of evidence). We did not perform network meta-analysis on multiple pregnancy due to high inconsistency. Pairwise meta-analyses showed an RR for multiple pregnancy rates of 9.11(95% CI 1.18-70.32) comparing IUI with gonadotrophins to natural cycle IUI. There was no data available on multiple pregnancy rates following IUI with CC or Letrozole compared to natural cycle IUI. The RR for multiple pregnancy rates comparing gonadotrophins to CC was 1.42 (95% CI 0.68-2.97), comparing Letrozole to CC was 0.97 (95% CI 0.47-2.01) and comparing Letrozole to gonadotrophins was 0.29 (95% CI 0.14-0.58).In a meta-analysis among studies with adherence to strict cancellation criteria, the RR for live births/ongoing pregnancy rates comparing gonadotrophins to CC was 1.20 (95% CI 0.95-1.51) and the RR for multiple pregnancy rates comparing gonadotropins to CC was 0.80 (95% CI 0.38-1.68). WIDER IMPLICATIONS: Based on low to moderate quality of evidence in this network meta-analysis, IUI with gonadotrophins ranked highest on live birth/ongoing pregnancy rates, but women undergoing this treatment protocol were also at risk for multiple pregnancies with high complication rates. IUI regimens with adherence to strict cancellation criteria led to an acceptable multiple pregnancy rate without compromising the effectiveness. Within a protocol with adherence to strict cancellation criteria, gonadotrophins seem to improve live birth/ongoing pregnancy rates compared to CC. We, therefore, suggest performing IUI with ovarian stimulation using gonadotrophins within a protocol that includes strict cancellation criteria. Obviously, this ignores the impact of costs and patients preference.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Gonadotropinas/uso terapêutico , Inseminação Artificial/métodos , Letrozol/uso terapêutico , Indução da Ovulação/métodos , Feminino , Humanos , Infertilidade/terapia , Nascido Vivo , Metanálise em Rede , Gravidez , Taxa de Gravidez , Gravidez Múltipla/estatística & dados numéricos
9.
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 , Nascido 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
10.
Horm Mol Biol Clin Investig ; 41(1)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782947

RESUMO

Background To determine whether a minimal stimulation (MS) or high-dose stimulation (HDS) protocol is a better option for patients classified as poor ovarian responders (POR) in terms of reproductive and pregnancy outcomes. Materials and methods A database search for evaluation of the study outcome by using meta-analysis method was carried out. The primary outcome was the clinical pregnancy (CP) rate for each of two groups, namely, the MS and HDS groups. The secondary outcomes were the gonadotropin dose used, duration of stimulation, cancellation rate, number of oocytes retrieved, number of fertilized oocytes, number of embryos transferred and live birth rates. Results Across five databases, 4670 potential studies for further screening were selected. But ultimately only six studies, three RCTs and three retrospective or case control studies were selected that meet the Bologna criteria for POR. In all there were 624 cycles. Our meta-analysis indicated that the CP rates, cycle cancellation rates, durations of stimulation, numbers of oocytes fertilized and numbers of embryos transferred were not statistically significant. Clearly, the number of oocytes retrieved in the MS group was significantly lower than in the HDS group, while the HDS group consumed significantly higher doses of gonadotropins than the MS group. The live birth rates were significantly higher in the MS group than in the HDS group. Conclusion MS should be the first-line protocol for managing POR because the live birth rate is significantly higher, even with fewer oocytes retrieved.


Assuntos
Fertilização In Vitro/métodos , Indução da Ovulação/métodos , Coeficiente de Natalidade , Feminino , Gonadotropinas/administração & dosagem , Gonadotropinas/uso terapêutico , Humanos , Nascido Vivo , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
11.
Hum Reprod Update ; 25(6): 717-732, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31647106

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06). WIDER IMPLICATIONS: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Letrozol/uso terapêutico , Metformina/uso terapêutico , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/terapia , Coeficiente de Natalidade , Feminino , Gonadotropinas/uso terapêutico , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Nascido Vivo , Indução da Ovulação/efeitos adversos , Gravidez , Taxa de Gravidez , Gravidez Múltipla
12.
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
13.
Hum Reprod Update ; 25(5): 541-563, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31304974

RESUMO

BACKGROUND: In the context of increasing rates of overweight and obesity in young adult women, and the increasing numbers of women seeking help for fertility problems, it is important to understand whether physical activity (PA) could help with management of reproductive health problems, with or without weight loss. OBJECTIVE AND RATIONALE: The primary aim of this systematic review and meta-analysis was to assess the effects of PA on selected reproductive health outcomes in young adult women, in order to inform best practice advice for women in terms of promoting fertility and reproductive health in young adulthood. SEARCH METHODS: An electronic search of PubMed, EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science, SportDiscus, and Cochrane was performed for studies published between January 2000 and May 2018. Keywords and Medical Subject Headings terms related to PA, reproductive health, and weight gain were used. Studies were selected if they were intervention studies, if PA was delivered as part of an intervention to pre-menopausal women, and if any reproductive health outcome was reported. Quality analysis was performed using the Tool for the assEssment of Study qualiTy and reporting in EXercise. OUTCOMES: Eighteen studies, with a mix of four types of study design (4 randomized controlled trials (RCTs), 11 randomized comparison trials, 2 non-randomized comparison trials, and 1 single-arm clinical trial), were identified. Comparisons included fertility treatment (four studies) and common treatments for women with polycystic ovary syndrome (PCOS) symptoms (nine studies). Pooled analysis of data from three of the four studies with a control group showed higher pregnancy [risk ratio (RR) 2.10, 95% CI (1.32, 3.35); three studies] and live birth [RR 2.11, 95% CI (1.02, 4.39); two studies] rates in the intervention groups compared with non-therapy controls. Aggregated data from the fertility treatment comparative studies (i.e. those that compared PA with standard fertility treatment such as clomiphene, gonadotrophins, and/or IVF) showed no significant intervention differences: RR 1.46, 95% CI (0.87, 2.45) for clinical pregnancy (four studies) and RR 1.09, 95% CI (0.56, 2.12) for live births (two studies). Pooled analysis from the comparison trials that used pharmaceutical or dietary treatment for PCOS as comparison showed higher pregnancy rates [RR 1.59, 95% CI (1.06, 2.38); five studies] and live birth rates [RR 2.45, 95% CI (1.24, 4.83); two observations] in the PA intervention groups than in the comparison groups. Analysis of other outcomes, such as ovulation rates, menstrual regularity, and conception rates, showed no differences between the PA intervention and comparison groups. WIDER IMPLICATIONS: There is emerging evidence from RCT that PA may improve pregnancy rates in women with reproductive health problems. Comparative studies indicate that PA intervention may be as effective as other commonly used clinical intervention strategies for improving reproductive health outcomes. While the type, intensity, frequency, and duration of optimal PA intervention, and the role of PA independent of weight loss, remain unclear, these preliminary findings suggest that PA may be an affordable and feasible alternative or complementary therapy to fertility treatments.


Assuntos
Terapia por Exercício/métodos , Exercício Físico/fisiologia , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Saúde Reprodutiva , Adulto , Coeficiente de Natalidade , Clomifeno/uso terapêutico , Feminino , Gonadotropinas/uso terapêutico , Humanos , Nascido Vivo , Menstruação/fisiologia , Síndrome do Ovário Policístico/terapia , Gravidez , Taxa de Gravidez , Adulto Jovem
14.
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
15.
Clin Med (Lond) ; 19(4): 350-352, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31308123

RESUMO

Some fertility patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian hyperstimulation (COH) experience ceased follicular growth during COH and fail to superovulate. In this article, 24 such PCOS patients resumed COH 15-20 days after previous COH treatment was stopped while patients were under ovarian downregulation. Seventeen cases achieved oocyte retrieval, of which 14 underwent embryo transfer and 12 resulted in clinical pregnancy. The remaining seven cases saw ceased follicular growth at 13 mm. This provides a rescue protocol for failed COH patients with PCOS.


Assuntos
Indução da Ovulação , Síndrome do Ovário Policístico , Adulto , Transferência Embrionária , Feminino , Fertilização In Vitro , Gonadotropinas/administração & dosagem , Gonadotropinas/uso terapêutico , Humanos , Infertilidade Feminina/terapia , Folículo Ovariano/fisiologia , Indução da Ovulação/efeitos adversos , Indução da Ovulação/estatística & dados numéricos , Doença Inflamatória Pélvica , Falha de Tratamento , Adulto Jovem
16.
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
17.
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
18.
Asian J Androl ; 21(6): 623-627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31062720

RESUMO

Hypogonadotropic hypogonadism (HH) is a rare disease in which medical treatment has a high success rate to achieve fertility. This study aimed to analyze the efficacy of hormone replacement therapy and determine predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH. A total of 112 patients with low testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy. During treatment, 96 (85.7%) patients had sperm present in ejaculate samples. Among these patients, 72 were married and wanted a child. Of these 72 patients, 48 (66.7%) of couples had pregnancies from natural conception. After initiation of treatment, the mean time for the appearance of sperm in semen was 9.48 months. There were no significant differences between baseline FSH, T, and LH levels; however, older age, larger testicular size, and low rate of undescended testes were favorable factors for successful spermatogenesis. Larger testicular size and older age were also the main predictive factors for natural conception. We found that patients with undescended testes had a younger age, smaller testes, and lower T levels compared with patients exhibiting descended testes. The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis (73.7% vs 87.6%, P = 0.261). The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.


Assuntos
Hormônio Foliculoestimulante/uso terapêutico , Gonadotropinas/uso terapêutico , Terapia de Reposição Hormonal/métodos , Hipogonadismo/tratamento farmacológico , Hormônio Luteinizante/uso terapêutico , Adolescente , Adulto , Gonadotropina Coriônica/uso terapêutico , Hormônio Foliculoestimulante/análogos & derivados , Humanos , Hipogonadismo/sangue , Hipogonadismo/patologia , Hormônio Luteinizante/análogos & derivados , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espermatogênese/efeitos dos fármacos , Adulto Jovem
19.
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
20.
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
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