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1.
Niger J Clin Pract ; 22(11): 1463-1466, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31719265

RESUMO

Objective: To identify whether red blood cell distribution width coefficient of variation (RDW-CV) and mean platelet volume (MPV) levels can predict clomiphene citrate resistance (CC-R) in infertile, anovulatory females with polycystic ovarian syndrome (PCOS). Methods: A total of 89 infertile patients who were admitted to a tertiary center diagnosed with non-obese PCOS were included in this study. The patients were divided into two groups: the first group comprised 53 non-obese patients with PCOS and CC-R, and the second group included 36 non-obese patients with PCOS and CC-S. RDW-CV, RDW-SD, and MPV values, along with routine whole blood count parameters were compared between the groups. Results: RDW-CV values were found to be significantly higher in the patients with CC-R compared to those with CC-S (P < 0.05). The sensitivity, specificity, positive, and negative predictive values were found to be 69%, 58.1%, 34.5%, and 12.5%, respectively, at an RDW-CV level of 12.85. The odds ratio was calculated as 3.077 (95% CI 1.245-7.603) in terms of the cut-off point. Conclusion: We think that RDW-CV which is a marker of inflammation is a simple, cheap, and accessible marker for the prediction of CC resistance.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Inflamação/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Biomarcadores/sangue , Clomifeno/administração & dosagem , Contagem de Eritrócitos , Feminino , Humanos , Indução da Ovulação , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
2.
Rev Assoc Med Bras (1992) ; 65(9): 1144-1150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618328

RESUMO

OBJECTIVE: In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS: A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS: The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION: The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Muco do Colo Uterino/efeitos dos fármacos , Clomifeno/farmacologia , Quimioterapia Combinada , Endométrio/fisiopatologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Folículo Ovariano/efeitos dos fármacos , Indução da Ovulação , Proteína de Ligação a Elemento Regulador de Esterol 1/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Adulto Jovem
3.
Int J Gynaecol Obstet ; 147(1): 59-64, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31273783

RESUMO

OBJECTIVE: To compare clinical and metabolic profiles between N-acetylcysteine and l-carnitine among women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). METHODS: A randomized trial at Zagazig University between January 2017 and March 2018. Women with CC-resistant PCOS were allocated randomly to receive CC plus N-acetylcysteine or CC plus l-carnitine. The primary outcome was clinical pregnancy rate; secondary outcomes were ovulation rate and metabolic changes. RESULTS: Overall, 162 women completed the study (N-acetylcysteine group, n=82; l-carnitine group, n=80). After 3 months, there was no difference in pregnancy (P=0.15), ovulation (P=0.21), or spontaneous abortion (P=0.11) rates between the two groups. There was no significant decrease in BMI in either group (both P>0.05). There were improvements in menstrual pattern, follicle-stimulating hormone, luteinizing hormone, free testosterone, and insulin resistance markers in both groups (all P<0.05). An improvement in lipid profile was observed only in the l-carnitine group (P<0.001). N-Acetylcysteine treatment led to significantly greater improvement in free testosterone and insulin resistance parameters as compared with l-carnitine (all P<0.05). CONCLUSIONS: Both N-acetylcysteine and l-carnitine were equally effective in improving pregnancy and ovulation rates among women with CC-resistant PCOS. However, N-acetylcysteine was superior in ameliorating insulin resistance and only l-carnitine improved lipid profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03164421.


Assuntos
Acetilcisteína/uso terapêutico , Carnitina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Clomifeno/uso terapêutico , Método Duplo-Cego , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Resistência à Insulina , Ovulação/efeitos dos fármacos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-31343980

RESUMO

Clomiphene citrate is a first-line drug for the induction of ovulation in infertility cases. Leukocytoclastic vasculitis (LCV) is an extremely rare serious adverse drug reaction to clomiphene. We report here the case of a 30-year-old Indian female patient who presented with generalized petechiae and palpable purpura without fever and sparing the mucosa, temporally related to clomiphene intake and consistent with LCV histologically. Clomiphene was stopped and the patient was treated symptomatically with prednisolone 40 mg/day, oral levocetirizine 5 mg twice daily, and emollients and calamine lotion topically. The patient improved over 3-4 weeks. The prednisolone dose was tapered weekly and withdrawn gradually. To date, drug-induced LCV has not been previously reported with clomiphene. Although rare, clomiphene could be considered a potential cause of drug-induced cutaneous LCV in the differential diagnosis of erythematosus rash with non-blanching petechiae and purpura.


Assuntos
Clomifeno/efeitos adversos , Vasculite Leucocitoclástica Cutânea/induzido quimicamente , Adulto , Clomifeno/uso terapêutico , Feminino , Humanos , Ovulação/efeitos dos fármacos
5.
Med Sci Monit ; 25: 3910-3917, 2019 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-31129677

RESUMO

BACKGROUND Polycystic ovary syndrome (PCOS) is associated with infertility or subfertility due to impaired ovulation. Clomiphene citrate is a first-line treatment option for the induction of ovulation in women with PCOS. The study aimed to compare markers of oxidative stress or the total oxidative status (TOS), total antioxidant status (TAS), and levels of paraoxonase-1 (PON-1) before and after day 21 of the menstrual cycle in women with PCOS treated with clomiphene citrate to induce ovulation. MATERIAL AND METHODS The study included 75 women who were divided into a control group (n=25) that included healthy untreated women, untreated women with PCOS (n=24) who had spontaneous ovulation, and women with PCOS who were treated with clomiphene citrate for subfertility or infertility (n=26) (the PCOS-CC group). The study group was treated for five days with clomiphene citrate (50 mg/day). Peripheral venous blood was sampled on day 3 and day 21 of the menstrual cycle from women in all three groups, and TAS, TOS, and PON-1 levels were measured. RESULTS In all three groups, TAS and PON levels were significantly reduced and TOS values were significantly increased on day 21 of the menstrual cycle. Comparison of TAS, TOS, and PON-1 levels between the three study groups on day 3 and day 21 of the menstrual cycle showed no significant difference (p=0.600, p=0.223, p=0.956, respectively). CONCLUSIONS This study showed that spontaneous ovulation occurs in association with an oxidative state in healthy women and women with PCOS, and women with PCOS following treatment with clomiphene citrate.


Assuntos
Clomifeno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Síndrome do Ovário Policístico/metabolismo , Adulto , Antioxidantes , Arildialquilfosfatase/análise , Arildialquilfosfatase/sangue , Estudos de Casos e Controles , Clomifeno/uso terapêutico , Feminino , Humanos , Infertilidade Feminina/tratamento farmacológico , Indução da Ovulação/métodos , Oxirredução/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto Jovem
6.
Eur J Obstet Gynecol Reprod Biol ; 238: 104-109, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31128532

RESUMO

OBJECTIVE: To determine the effect of a 3-month course of clomiphene citrate (CC) on plasma testosterone (T) level and on semen parameters in 18 infertile men with low T level and normal or low gonadotropines level. STUDY DESIGN: A retrospective study was conducted by reviewing the medical records of men referred to a university fertility medicine unit for infertility management between January 2010 and March 2015. Men treated with CC for at least 3 months were included if they presented with: RESULTS: 18 patients met the inclusion criteria. CC was prescribed for 3 months at the dose of 50 mg every 48 h. Plasma T level was assessed at baseline and after 1 month of CC administration. Semen parameters were assessed at baseline and after 3 months of CC administration. The median pre-treatment T level was 9.1 nmol/l; after 1 month of CC treatment the median post-treatment T level increased to 20.2 nmol/l (p = <0.001). Median baseline sperm concentration was 7 millions/ml with a median progressive motility of 18%. After 3 months of CC, the median post-treatment sperm concentration was 17.5 millions/ml (p = 0.024) and the median post-treatment progressive sperm motility was 18% (p = 0.40). Three natural pregnancies occurred during the treatment period. CONCLUSION: CC is an effective and inexpensive treatment to increase plasma T level in infertile men with low T level and normal or low gonadotropines level. Our study suggests that CC could increase sperm concentration even in oligospermic infertile men, without, however, a significant effect on progressive sperm motility. More powered randomized controlled trials are needed to definitively assess CC effect on sperm parameters and on natural pregnancy rates.


Assuntos
Clomifeno/uso terapêutico , Gonadotropinas/sangue , Infertilidade Masculina/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Testosterona/sangue , Adulto , Humanos , Infertilidade Masculina/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise do Sêmen , Adulto Jovem
7.
J Neurooncol ; 143(1): 137-144, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30868355

RESUMO

PURPOSE: Meningiomas are more common in females and 70-80% express the progesterone receptor, raising the possibility that high-dose exogenous estrogen/progesterone exposure, such as occurs during fertility treatments, may increase the risk of developing a meningioma. The goal of this study was to report the incidence of prior fertility treatment in a consecutive series of female meningioma patients. METHODS: A retrospective review (2015-2018) was performed of female patients with meningioma, and those with prior fertility treatment were compared to those without fertility treatment using standard statistical methods. RESULTS: Of 206 female patients with meningioma, 26 (12.6%) had a history of fertility treatments. Patients underwent various forms of assisted reproductive technology including: in vitro fertilization (50.0%), clomiphene with or without intrauterine insemination (34.6%), and unspecified (19.2%). Median follow up was 1.8 years. Tumors were WHO grade I (78.6%) or grade II (21.4%). Patients who underwent fertility treatments presented at significantly younger mean age compared to those who had not (51.8 vs. 57.3 years, p = 0.0135, 2-tailed T-test), and on multivariate analysis were more likely to have multiple meningiomas (OR 4.97, 95% CI 1.4-18.1, p = 0.0154) and convexity/falx meningiomas (OR 4.45, 95% CI 1.7-11.5, p = 0.0021). CONCLUSIONS: Patients in this cohort with a history of fertility treatment were more likely to present at a younger age and have multiple and convexity/falx meningiomas, emphasizing the importance of taking estrogen/progesterone exposure history when evaluating patients with meningioma. Future clinical studies at other centers in larger populations and laboratory investigations are needed to determine the role of fertility treatment in meningioma development.


Assuntos
Infertilidade Feminina/epidemiologia , Infertilidade Feminina/terapia , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Técnicas de Reprodução Assistida , Adulto , Idade de Início , Idoso , Clomifeno/efeitos adversos , Clomifeno/uso terapêutico , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Fármacos para a Fertilidade Feminina/uso terapêutico , Seguimentos , Humanos , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Meningioma/metabolismo , Meningioma/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Técnicas de Reprodução Assistida/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
8.
J Clin Pharm Ther ; 44(4): 618-622, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30868612

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Letrozole is widely known for its use as an ovulation inductor. This study aims to investigate the effects of letrozole and clomiphene citrate in females with polycystic ovarian syndrome. METHODS: This is a randomized non-blinded controlled trial study that included 80 infertile females with polycystic ovarian syndrome receiving a standard dose of either clomiphene citrate or letrozole on day 2 of the cycle. An ultrasound was done to examine growth of the follicle, endometrial thickness on days 12-13, and a Doppler study to measure resistance index (RI), pulsatility index and ratio of systolic/diastolic velocity. RESULTS AND DISCUSSION: The mean levels of dominant follicle and oestradiol were significantly higher in the clomiphene citrate group than in the letrozole group. The letrozole group had a significantly greater endometrial thickness than the clomiphene citrate group. The resistance index and pulsatility index were lower in the letrozole group and in pregnant women than in the clomiphene citrate group and the non-pregnant group. WHAT IS NEW AND CONCLUSION: The use of letrozole for ovulation induction in polycystic ovarian syndrome patients has a better effect on endometrial receptivity markers when compared to clomiphene citrate.


Assuntos
Inibidores da Aromatase/uso terapêutico , Clomifeno/uso terapêutico , Endométrio/efeitos dos fármacos , Letrozol/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Feminino , Humanos , Infertilidade Feminina/tratamento farmacológico , Folículo Ovariano/efeitos dos fármacos , Indução da Ovulação/métodos , Estudos Prospectivos
9.
Reprod Biol Endocrinol ; 17(1): 17, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728032

RESUMO

The objective of this systematic review was to examine the literature and to compare the effectiveness of letrozole (LE) versus laparoscopic ovarian drilling (LOD) for the induction of ovulation in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). The PUBMED, Web of Science, and EMBASE databases were searched systematically for eligible randomized controlled trials (RCTs) from English language articles published from database inception to September 2018. Data were independently extracted and analyzed using the fixed-effects model or random-effects model according to the heterogeneity of the data. Four RCTs including 621 patients (309 in the LE group and 312 in the LOD group) met the inclusion criteria. There were no differences with regard to ovulation rate (relative risk [RR] 1.12; 95% confidence interval [CI] 0.93 to 1.34; P = 0.12, I2 = 90%, 541 patients, three studies), pregnancy rate (RR 1.21; 95% CI 0.95 to 1.53; P = 0.12, I2 = 0%, 621 patients, four studies), live birth rate (RR 1.27; 95% CI 0.96 to 1.68; P = 0.09, I2 = 19%, 541 patients, three studies), and abortion rate (RR 0.7; 95% CI 0.3 to 1.61; P = 0.40, I2 = 0%, 621 patients, four studies) between the two groups. These results indicated that LE and LOD appear to be equally effective in achieving live birth rate in patients with CC-resistant PCOS.


Assuntos
Clomifeno/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Laparoscopia/métodos , Letrozol/uso terapêutico , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/complicações , Inibidores da Aromatase/uso terapêutico , Coeficiente de Natalidade , Resistência a Medicamentos , Feminino , Fármacos para a Fertilidade Feminina/uso terapêutico , Humanos , Infertilidade Feminina/etiologia , Gravidez , Resultado da Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Andrologia ; 51(5): e13257, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30779195

RESUMO

Clomiphene citrate (CC) is commonly used off-label for the treatment of male infertility, yet there is limited data to guide patient selection. To identify a subset of patients more likely to benefit from CC, we aimed to define predictors of improvement in semen parameters among men receiving CC. We retrospectively analysed 151 men treated with at least 25 mg CC daily for male infertility and/or hypogonadism at two institutions between 2004 and 2014. Men previously on testosterone were excluded. The primary outcome was change in semen parameters. Variables included baseline patient characteristics, pre-treatment hormone profiles and pre-treatment semen analyses. A total of 77 men met inclusion criteria. Median length of therapy was 2.8 months. There was significant improvement in sperm concentration (14-21 million/ml; p = 0.002) and total motile count (TMC; 13-28 million; p = 0.04). One third of patients who began with fewer than 5 million motile spermatozoon improved to a TMC > 5 million, increasing reproductive options to include intrauterine insemination. Patient characteristics, pre-treatment hormone profile and degree of oligozoospermia did not predict treatment response. While no predictors of improvement were identified, clinically useful response rates are described for use in shared decision-making.


Assuntos
Clomifeno/uso terapêutico , Hipogonadismo/tratamento farmacológico , Infertilidade Masculina/tratamento farmacológico , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Adulto , Clomifeno/farmacologia , Hormônio Foliculoestimulante/sangue , Humanos , Hipogonadismo/sangue , Infertilidade Masculina/sangue , Hormônio Luteinizante/sangue , Masculino , Uso Off-Label , Estudos Retrospectivos , Testosterona/sangue , Resultado do Tratamento
12.
Obstet Gynecol ; 133(3): 437-444, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30741800

RESUMO

OBJECTIVE: To estimate the clinical effectiveness, as determined by positive pregnancy test, of letrozole compared with clomiphene citrate for ovarian stimulation in patients with unexplained infertility. DATA SOURCES: We conducted a systematic review and meta-analysis of data from electronic databases including Ovid-MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and ClinicalTrials.gov. METHODS: We searched for concepts of unexplained infertility, letrozole, clomiphene citrate, and clinical outcomes including pregnancy and live birth. Studies were included if they were randomized controlled trials (RCTs) comparing clomiphene citrate with letrozole in patients with unexplained infertility. Eight RCTs including 2,647 patients with unexplained infertility were included. Primary outcome was positive pregnancy test per patient. Secondary outcomes included positive pregnancy test per cycle, clinical pregnancy, live birth, spontaneous miscarriage, twin gestation, mean serum estradiol (E2), endometrial thickness, and number of dominant follicles. The Cochrane Q test and Higgin's I were used to assess heterogeneity. Random effects models were used to obtain pooled relative risks (RR) and 95% CIs. TABULATION, INTEGRATION, AND RESULTS: In analysis per patient, there was no significant difference in positive pregnancy test between patients treated with letrozole compared with clomiphene citrate (24% vs 23%, pooled RR 1.08, 95% CI 0.85-1.36). Significant heterogeneity was noted between studies (I=60.8%). There were no significant differences in clinical pregnancy (pooled RR 1.15, 95% CI 0.71-1.85), live birth (pooled RR 0.94, 95% CI 0.83-1.08), spontaneous miscarriage (pooled RR 0.92, 95% CI 0.61-1.38), or twin gestation (pooled RR 0.81, 95% CI 0.39-1.68). Mean serum E2 was significantly lower in the letrozole group than in the clomiphene citrate group. CONCLUSION: Although limited by heterogeneity, studies of ovarian stimulation in women with unexplained infertility show no difference in clinical outcomes between letrozole and clomiphene citrate.


Assuntos
Inibidores da Aromatase/uso terapêutico , Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Letrozol/uso terapêutico , Aborto Espontâneo/epidemiologia , Estradiol/sangue , Feminino , Humanos , Infertilidade Feminina/sangue , Nascimento Vivo , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Gravidez de Gêmeos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Gynecol Endocrinol ; 35(8): 701-705, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30806102

RESUMO

To evaluate the reproductive and metabolic effects of L-carnitine plus metformin in clomiphene citrate (CC) resistant obese polycystic ovary syndrome (PCOS) women. A double-blinded randomized controlled clinical trial, clomiphene-citrate resistant obese women were allocated randomly to receive CC plus metformin and L-carnitine (n = 138) or CC plus metformin and placebo (n = 136). The primary outcome was clinical pregnancy rate. The secondary outcomes were hormonal and metabolic profile changes in addition to ovulation and first trimester (13 weeks) miscarriage rates. Clomiphene-citrate, L-carnitine, and metformin group showed significant improvement in the menstrual regularity, ovulation rate, and pregnancy rate compared to CC plus metformin and placebo group (29% vs. 9%, 34.7% vs.11%, and 28.2% vs. 6.6%, respectively). No statistically significant difference in the miscarriage rate between the two groups (p = .08). After three months of treatment, the reduction in body mass index (BMI) was non-significant (p = .061) between both groups. The hormonal and metabolic parameters were more significantly improved in the L-carnitine group compared with the placebo group. l-Carnitine may act synergistically with metformin for improvement of reproductive performance, insulin resistance, and lipid profile in clomiphene-resistant obese PCOS women.


Assuntos
Carnitina/administração & dosagem , Clomifeno/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Metformina/administração & dosagem , Obesidade/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Feminino , Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônios/metabolismo , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/metabolismo , Infertilidade Feminina/fisiopatologia , Resistência à Insulina/fisiologia , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Taxa de Gravidez , Reprodução/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
14.
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
15.
Sex Med Rev ; 7(2): 272-276, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30522888

RESUMO

INTRODUCTION: Clomiphene citrate (CC) is a selective estrogen receptor modulator that has been used for the treatment of hypogonadism in men since the 1970s. It acts centrally to increase secretion of luteinizing hormone and follicle-stimulating hormone, thereby increasing testosterone production and serum levels. Unlike testosterone replacement therapy, CC does not suppress the hypothalamic-pituitary-gonadal axis, preserving intratesticular testosterone production and spermatogenesis. This is especially useful in treating hypogonadal men who are interested in fertility. AIM: To review the literature regarding the use of CC in the setting of hypogonadism. METHODS: A review of the relevant literature through September 2018 was performed via PubMed. MAIN OUTCOME MEASURE: The data regarding the efficacy and safety of CC when used in the setting of hypogonadism is summarized. RESULTS: Although results are mixed, many studies show CC reduces symptoms in hypogonadal men. Studies have also shown improvement in erectile function and bone mineral density, as well as a reduction in body mass index. There have been few studies investigating fertility rates in hypogonadal men treated with CC, but a metaanalysis of these shows significant improvement in fertility rates. Several studies show improvement in semen parameters. Few studies have investigated adverse effects of the drug. Reports include headache, dizziness, gynecomastia, and exacerbation of psychiatric illnesses. Despite these reports, CC is generally considered to be safe and well tolerated. CONCLUSION: CC is safe and effective and should remain in the armament of urologists treating hypogonadal men, especially men interested in preservation of fertility. Wheeler KM, Sharma D, Kavoussi PK, et al. Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev 2019;7:272-276.


Assuntos
Clomifeno/uso terapêutico , Hipogonadismo/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Clomifeno/efeitos adversos , Feminino , Fertilidade/efeitos dos fármacos , Humanos , Masculino
16.
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
17.
Gynecol Endocrinol ; 35(3): 217-219, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30324834

RESUMO

A prospective observational study was conducted on 186 patients with clomifene citrate (CC)-resistant polycytic ovary syndrome (PCOS) who were allocated into two treatment arms for three months; letrozole alone (n = 92) and letrozole with luteal support using vaginal dydrogestrone (n = 94). Patients received luteal support experienced significantly higher clinical pregnancy rate than those who received letrozole alone (48.9% vs. 23.9%, respectively). Luteal support in letrozole treated CC-resistant PCOS significantly improves pregnancy rate and should be implemented in ovulation induction regimens.


Assuntos
Didrogesterona/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Letrozol/uso terapêutico , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Progestinas/uso terapêutico , Administração Intravaginal , Adulto , Clomifeno/uso terapêutico , Didrogesterona/administração & dosagem , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Humanos , Gravidez , Taxa de Gravidez , Progestinas/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
18.
Urol J ; 16(1): 78-82, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30033514

RESUMO

PURPOSE: To evaluate the efficacy of therapy with spirulina supplement on semen parameters in patients with idiopathic male infertility. MATERIALS AND METHODS: A total of 40 men with idiopathic infertility were randomly assigned into two groups. Group A received 2 g spirulina supplement as well as conventional regimen for the treatment of infertility selected by their physician (220 mg/day zinc sulfate, 500mg/day L-carnitine, and 50 mg/day clomiphene) during 12 weeksof the study, while group B received placebo plus conventional therapy during the study period. Semen parameters were analyzed at baseline and at the end of the study as a primary endpoint. The secondary endpoint was the rate of pregnancy occurring in the patients. wives. RESULT: No significant differences in semen parameters were observed between the spirulina and control groups [count (16.43 vs. 46.00, P = .164), motility (51.00 vs. 48.7, P = .008), and morphology (47.50 vs. 15.00, P = NA)]. Our results showed a pregnancy rate of 5% in the spirulina group versus 0% in the control group. CONCLUSION: This pilot randomized trial provides initial evidence on the possible beneficial effects of spirulina mainly in patients with impaired sperm motility or morphology. Due to the limited sample size, further larger randomized trials not only at the level of semen parameters but at the scope of paternity are required to confirmthese potential benefits.


Assuntos
Infertilidade Masculina/terapia , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides/patologia , Spirulina , Adulto , Carnitina/uso terapêutico , Clomifeno/uso terapêutico , Suplementos Nutricionais , Antagonistas de Estrogênios/uso terapêutico , Feminino , Humanos , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Projetos Piloto , Gravidez , Taxa de Gravidez , Análise do Sêmen , Adulto Jovem , Sulfato de Zinco/uso terapêutico
19.
Gynecol Endocrinol ; 35(1): 86-89, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30044165

RESUMO

Clomiphene citrate (CC) is the agent of first choice in polycystic ovarian syndrome; however, anovulation problem does not resolve in a quarter of them. Thus, we investigated the value of anti-Müllerian hormone (AMH) in the prediction of ovarian response to CC in women with the polycystic ovarian syndrome (PCOS). This prospective cohort study included 90 anovulatory women with PCOS who were given 50 mg/d CC. The patients who ovulated occupied the group of responders and the patients who did not ovulate in three cycles included in the CC-resistant group. AMH levels of both groups were compared. p < .05 was considered statistically significant. Patients who ovulated had significantly lower serum AMH concentrations compared with the resistant group (p = .001). After analyzing the ROC curve, serum AMH concentration was found to be a useful predictor of CC resistance with the sensitivity of 66% and the specificity of 89%, when the threshold AMH concentration was >12.38 ng/ml in PCOS patients. In the present study, we revealed that the higher the AMH level the poorer the CC response would be in PCOS patients, therefore we recommend measuring the AMH levels of all PCOS patients before planning any ovulation induction treatment to achieve the desired success.


Assuntos
Hormônio Antimülleriano/sangue , Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Síndrome do Ovário Policístico/sangue , Adulto , Feminino , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Estudos Prospectivos , Falha de Tratamento , Resultado do Tratamento , Adulto Jovem
20.
Cochrane Database Syst Rev ; 12: CD012378, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30570133

RESUMO

BACKGROUND: Subfertile women are highly motivated to try different adjunctive therapies to have a baby, and the widespread perception is that dietary supplements such as myo-inositol (MI) and D-chiro-insoitol (DCI) are associated with only benefit, and not with harm. Many fertility clinicians currently prescribe MI for subfertile women with polycystic ovary syndrome (PCOS) as pre-treatment to in vitro fertilisation (IVF) or for ovulation induction; however no high-quality evidence is available to support this practice. This review assessed the evidence for the effectiveness of inositol in subfertile women with a diagnosis of PCOS. OBJECTIVES: To evaluate the effectiveness and safety of oral supplementation of inositol for reproductive outcomes among subfertile women with PCOS who are trying to conceive. SEARCH METHODS: We searched the following databases (to July 2018): Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. We also checked reference lists and searched the clinical trials registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type, dose, or combination of oral inositol versus placebo, no treatment/standard treatment, or treatment with another antioxidant, or with a fertility agent, or with another type of inositol, among subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible studies, extracted data, and assessed risk of bias. The primary outcomes were live birth and adverse effects; secondary outcomes included clinical pregnancy rates and ovulation rates. We pooled studies using a fixed-effect model, and we calculated odds ratios (ORs) with 95% confidence intervals (CIs). We assessed the overall quality of the evidence by applying GRADE criteria. MAIN RESULTS: We included 13 trials involving 1472 subfertile women with PCOS who were receiving myo-inositol as pre-treatment to IVF (11 trials), or during ovulation induction (two trials). These studies compared MI versus placebo, no treatment/standard, melatonin, metformin, clomiphene citrate, or DCI. The evidence was of 'low' to 'very low' quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency, and lack of reporting of clinically relevant outcomes such as live birth and adverse events.We are uncertain whether MI improves live birth rates when compared to standard treatment among women undergoing IVF (OR 2.42, 95% CI 0.75 to 7.83; P = 0.14; 2 RCTs; 84 women; I² = 0%). Very low-quality evidence suggests that for subfertile women with PCOS undergoing pre-treatment to IVF who have an expected live birth rate of 12%, the rate among women using MI would be between 9% and 51%.We are uncertain whether MI may be associated with a decrease in miscarriage rate when compared to standard treatment (OR 0.40, 95% CI 0.19 to 0.86; P = 0.02; 4 RCTs; 535 women; I² = 66%; very low-quality evidence). This suggests that among subfertile women with PCOS with an expected miscarriage rate of 9% who are undergoing pre-treatment to IVF, the rate among women using MI would be between 2% and 8%; however this meta-analysis is based primarily on one study, which reported an unusually high miscarriage rate in the control group, and this has resulted in very high heterogeneity. When we removed this trial from the sensitivity analysis, we no longer saw the effect, and we noted no conclusive differences between MI and standard treatment.Low-quality evidence suggests that MI may be associated with little or no difference in multiple pregnancy rates when compared with standard treatment (OR 1.04, 95% CI 0.63 to 1.71; P = 0.89; 2 RCTs; 425 women). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected multiple pregnancy rate of 18%, the rate among women using inositol would be between 12% and 27%.We are uncertain whether MI may be associated with an increased clinical pregnancy rate when compared to standard treatment (OR 1.27, 95% CI 0.87 to 1.85; P = 0.22; 4 RCTs; 535 women; I² = 0%; very low-quality evidence). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected clinical pregnancy rate of 26%, the rate among women using MI would be between 24% and 40%. Ovulation rates were not reported for this comparison.Other comparisons included only one trial in each, so for the comparisons MI versus antioxidant, MI versus an insulin-sensitising agent, MI versus an ovulation induction agent, and MI versus another DCI, meta-analysis was not possible.No pooled evidence was available for women with PCOS undergoing ovulation induction, as only single trials performed comparison of the insulin-sensitising agent and the ovulation induction agent. AUTHORS' CONCLUSIONS: In light of available evidence of very low quality, we are uncertain whether MI improves live birth rate or clinical pregnancy rate in subfertile women with PCOS undergoing IVF pre-treatment taking MI compared to standard treatment. We are also uncertain whether MI decreases miscarriage rates or multiple pregnancy rates for these same women taking MI compared to standard treatment. No pooled evidence is available for use of MI versus placebo, another antioxidant, insulin-sensitising agents, ovulation induction agents, or another type of inositol for women with PCOS undergoing pre-treatment to IVF. No pooled evidence is available for use of MI in women undergoing ovulation induction.


Assuntos
Fertilização In Vitro , Infertilidade Feminina/tratamento farmacológico , Inositol/uso terapêutico , Síndrome do Ovário Policístico/complicações , Complexo Vitamínico B/uso terapêutico , Aborto Espontâneo/prevenção & controle , Administração Oral , Coeficiente de Natalidade , Clomifeno/uso terapêutico , Terapia Combinada/métodos , Feminino , Fármacos para a Fertilidade Feminina/uso terapêutico , Ácido Fólico/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Infertilidade Feminina/complicações , Nascimento Vivo/epidemiologia , Melatonina/uso terapêutico , Metformina/uso terapêutico , Indução da Ovulação , Gravidez , Gravidez Múltipla , Ensaios Clínicos Controlados Aleatórios como Assunto
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