RESUMO
Mitochondrial diseases include a group of maternally inherited genetic disorders caused by mutations in mtDNA. In most of these patients, mutated mtDNA coexists with wild-type mtDNA, a situation known as mtDNA heteroplasmy. Here, we report on a strategy toward preventing germline transmission of mitochondrial diseases by inducing mtDNA heteroplasmy shift through the selective elimination of mutated mtDNA. As a proof of concept, we took advantage of NZB/BALB heteroplasmic mice, which contain two mtDNA haplotypes, BALB and NZB, and selectively prevented their germline transmission using either mitochondria-targeted restriction endonucleases or TALENs. In addition, we successfully reduced human mutated mtDNA levels responsible for Leber's hereditary optic neuropathy (LHOND), and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP), in mammalian oocytes using mitochondria-targeted TALEN (mito-TALENs). Our approaches represent a potential therapeutic avenue for preventing the transgenerational transmission of human mitochondrial diseases caused by mutations in mtDNA. PAPERCLIP.
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Marcação de Genes , Doenças Mitocondriais/genética , Animais , Fusão Celular , DNA Mitocondrial , Embrião de Mamíferos/metabolismo , Endonucleases/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NZB , Doenças Mitocondriais/prevenção & controle , Mutação , Oócitos/metabolismoRESUMO
RESEARCH QUESTION: Do pregnancies with corpus luteum show different maternal and fetal plasma concentrations of the scavenger proteins haemopexin and α1-microglobulin compared with pregnancies without corpus luteum in preeclampsia? DESIGN: Case-control study of 160 singleton pregnancies: 54 naturally conceived, 50 by IVF after fresh embryo transfer or frozen embryo transfer (FET) in natural cycle (presence of corpus luteum) and 56 after fresh oocyte donation or FET in programmed cycles (absence of corpus luteum). Pregnancies were subclassified into normotensive, preeclampsia and severe preeclampsia cases. Heme-scavenger concentrations were measured by ELISA in maternal and cord plasma collected at delivery. RESULTS: After adjustment, maternal haemopexin was higher in IVF with corpus luteum than in naturally conceived pregnancies in normotensive (Pâ¯=â¯0.038) and preeclampsia (Pâ¯=â¯0.011) populations, and lower in preeclampsia for IVF pregnancies lacking corpus luteum compared with IVF with corpus luteum (Pâ¯=â¯0.002). Maternal α1-microglobulin levels were higher in the absence of corpus luteum only in severe cases of preeclampsia compared with naturally conceived pregnancies (Pâ¯=â¯0.014) and IVF with corpus luteum pregnancies (Pâ¯=â¯0.041). In cord blood, haemopexin was higher in IVF with corpus luteum compared with naturally conceived pregnancies in preeclampsia (Pâ¯=â¯0.039) and α1-microglobulin was higher in the group lacking corpus luteum compared with IVF with corpus luteum in the normotensive population (P < 0.001). CONCLUSIONS: The physiological differences shown for these heme-scavengers between pregnancies after embryo transfer in the presence or absence of corpus luteum support the hypothesis that corpus luteum activity could influence perinatal outcomes. Future research is needed on whether applying potential strategies to develop a corpus luteum might reduce the perinatal complications associated with programmed cycles of IVF.
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Pré-Eclâmpsia , alfa-Globulinas , Estudos de Casos e Controles , Corpo Lúteo , Transferência Embrionária/efeitos adversos , Feminino , Fertilização in vitro/efeitos adversos , Heme , Hemopexina , Humanos , Pré-Eclâmpsia/etiologia , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: Evaluate antral follicle count measured after pituitary suppression (AFCaps) with a GnRH agonist as predictor of ovarian response and cumulative live birth (CLB). METHODS: This study is a large cohort analysis of retrospective data between January 2011 and September 2020 in a tertiary-care university hospital. All first initiated IVF/ICSI cycles in women under 43 years of age for whom AFCaps was registered in our database were included. To evaluate CLB rates (CLBRs), only finalized cycles were analyzed (at least one live birth and/or all embryos transferred), excluding PGT cycles and severe male factor requiring testicular sperm extraction. RESULTS: AFCaps showed a good predictive ability in predicting ovarian response to ovarian stimulation. Predicting poor response, AFCaps presented an area under the receiver-operating characteristic curve (AUCROC) of 0.85 (95% CI 0.83-0.87), for high response prediction, the AUCROC was 0.80 (95% confidence interval [CI] 0.77-0.83).Although AFCaps was statistically higher in patients who achieved at least one live birth (13.6 ± 6.05 vs. 9.79 ± 6.33) and CLBRs per started cycle significantly increase between AFCaps quartiles (15.9%, 36.2%, 45.1% and 52.9%) its ability to predict CLBR was modest, with an AUCROC of 0.67 (95% CI 0.65-0.69). CONCLUSIONS: Women undergoing their first IVF/ICSI cycle following a long agonist GnRH protocol can be counseled with AFCaps measurement about their probability of achieving poor/high response. Based on this marker physicians can personalize ovarian stimulation with the aim of optimizing ovarian response and minimizing its risks. However, AFCaps has failed to predict CLB per started IVF cycle as an isolated marker.
Assuntos
Fertilização in vitro , Nascido Vivo , Gravidez , Masculino , Humanos , Feminino , Fertilização in vitro/métodos , Taxa de Gravidez , Estudos Retrospectivos , Regulação para Baixo , Sêmen , Coeficiente de Natalidade , Indução da Ovulação/métodos , Hormônio Liberador de GonadotropinaRESUMO
PURPOSE: The use of fertility preservation (FP) techniques has significantly increased in recent years in the assigned female at birth (AFAB) transgender population. Oocyte cryopreservation is the established method for FP, but ovarian tissue cryopreservation may be considered an alternative option, especially during gender-affirming surgery (GAS). The slow freezing (SF) cryopreservation technique is the standard method for human ovarian tissue, but recently, several studies have shown good results with the vitrification (VT) technique. The objective of this study was to compare the effectiveness of VT and SF techniques in ovarian tissue from AFAB transgender people. METHODS: This was a prospective study including 18 AFAB transgender people after GAS. Ovarian tissue pieces from each ovary were cryopreserved by SF and VT and compared with fresh tissue. Study by light microscopy (LM) assessed follicular morphology and density. The percentage of surviving and degenerated follicles was studied with the tissue viability test. Oocytes, granulosa cells and stroma were analysed separately by transmission electron microscopy. RESULTS: The VT technique preserves follicle and stromal tissue as well as the SF method, but with some differences. Evaluation by LM showed better follicle preservation with VT, but the ultrastructural study showed the presence of minor damage with both techniques compared to fresh tissue. CONCLUSION: Both cryopreservation techniques are accurate for maintaining the follicular population and stromal tissue. Further studies are needed to determine the impact of VT on ovarian tissue and the subsequent follicular activation mechanisms in AFAB ovarian tissue.
Assuntos
Pessoas Transgênero , Vitrificação , Criopreservação/métodos , Feminino , Congelamento , Humanos , Estudos Prospectivos , TestosteronaRESUMO
RESEARCH QUESTION: Could in-vitro action of follicles and fresh tissue autotransplantation without tissue culture (drug-free IVA) be useful in patients with primary ovarian insufficiency (POI)? DESIGN: Prospective observational cohort study in a tertiary university hospital. Drug-Free IVA was carried out in 14 women with POI with a median age of 33 years (29-36 years), median length of amenorrhoea of 1.5 years (1-11 years), median FSH levels 69.2 mIU/ml (36.9-82.8 mIU/ml) and anti-Müllerian hormone of 0.02 ng/ml (0.01-0.1 ng/ml). The surgical procedure included laparoscopic removal of ovarian cortex, fragmentation of tissue and autografting. Human menopausal gonadotrophin (HMG) was started immediately after surgery. RESULTS: Follicle development was detected in seven out of the 14 patients, and five women achieved successful oocyte retrieval. In six women, HCG was administered in 10 cycles. Six embryo transfers were carried out in five women resulting in four pregnancies; a clinical pregnancy rate of four in seven oocyte retrievals and four in six embryo transfers. CONCLUSIONS: Drug-free IVA could be a useful therapeutic option for patients with POI, leading to successful IVF outcomes.
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Recuperação de Oócitos , Ovário/transplante , Indução da Ovulação/métodos , Insuficiência Ovariana Primária/terapia , Transplante Autólogo/métodos , Adulto , Hormônio Antimülleriano/sangue , Transferência Embrionária , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Gravidez , Taxa de Gravidez , Insuficiência Ovariana Primária/sangueRESUMO
Objective: To analyze global outcomes in frozen-thawed embryo transfer according to endometrial preparation with natural cycle and artificial cycle taking into account the developmental stage of the embryo.Methods: Retrospective cohort study, held in a tertiary-care university hospital with 1265 cycles for frozen-thawed embryo transfer of 860 patients, performed between January 2014 and December 2017. A total of 1097 embryo transfers were performed: 163 transfers in natural cycle (N), 531 in artificial cycle: transdermal estrogens and 403 with oral estrogens.Results: Demographical factors were similar in the three groups studied. When comparing the number of embryos transferred, the quality and the stage of embryos within the three groups there were no differences. Implantation rates were significantly higher in natural cycle. When adjusted depending on the developmental stage, blastocyst embryos transferred in natural cycle preparation had the highest implantation rate. Multiple pregnancies were also higher in natural cycle preparation. There were no significant difference between the groups in the clinical pregnancy rate, ongoing pregnancy, live birth, and miscarriages.Conclusions: Our results suggest that a natural cycle endometrial preparation assessing the disappearance of the dominant follicle by ultrasound increases implantation rates, especially when transferring blastocysts.
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Implantação do Embrião/fisiologia , Transferência Embrionária/métodos , Estrogênios/administração & dosagem , Taxa de Gravidez , Adulto , Criopreservação , Feminino , Humanos , Gravidez , Estudos RetrospectivosRESUMO
The endometrium is one of a number of factors involved in achieving optimal outcomes after assisted reproductive treatment. Owing to its "passive" growth following adequate ovarian stimulation, it has received virtually no attention. Only when either endometrial thickness or ultrasonographic pattern seem inadequate have different strategies been assessed to try to improve it, especially in those cases where it seems difficult or impossible to make it grow. The objective of this review is to summarize the different strategies that have been investigated in patients with inadequate endometrium, to attempt to provide solid evidence of therapies that may be beneficial and to move away from empirism. A review of the existing literature was performed by searching MEDLINE, EMBASE, Cochrane library and Web of Science for publications in English related to refractory endometrium. Most current treatments are based on anecdotal cases and not on solid data, although worldwide many doctors and patients use them. In conclusion, this review found that it is not easy to provide a pragmatic, evidence-based approach to help physicians and patients confused by the available data on how to improve a poor endometrium. Honest balanced information provided to our patients is the best that we can do.
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Endométrio/patologia , Doenças Uterinas/terapia , Endométrio/fisiopatologia , Feminino , Humanos , Técnicas de Reprodução Assistida , Doenças Uterinas/fisiopatologiaRESUMO
PURPOSE: To evaluate the efficacy of luteal phase support with vaginal progesterone in women undergoing intrauterine insemination (IUI). METHODS: Systematic review and meta-analysis. Randomized controlled trials (RCT) comparing supplementation of luteal phase with vaginal progesterone among women undergoing IUI versus a control group were included. The main outcome assessed was live birth rate. RESULTS: Five RCT met the inclusion criteria. In all 1,271 patients were included (951 IUI cycles in the progesterone group, 935 in the control group). Women treated with vaginal progesterone achieved significantly higher live birth rate (risk ratio [RR] 1.94, 95 % confidence interval [CI] 1.36 to 2.77,), and clinical pregnancy rate (RR 1.41, 95 % CI 1.14 to 1.76) as compared with controls. In the subgroup analysis per stimulation protocol, this beneficial effect of receiving progesterone was only observed in the group stimulated with gonadotropins (RR 2.28, 95 % CI 1.49 to 3.51), compared to the group stimulated with clomiphene citrate (CC) (RR 1.30, 95 % CI 0.68 to 2.50). No differences were observed in the miscarriage and multiple pregnancy rates. CONCLUSIONS: The supplementation of luteal phase with vaginal progesterone significantly increases live birth among women undergoing IUI when receiving gonadotropins for ovulation induction. Women receiving CC to induce ovulation do not seem to benefit from this treatment.
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Infertilidade/terapia , Inseminação Artificial/métodos , Fase Luteal/efeitos dos fármacos , Progesterona/administração & dosagem , Administração Intravaginal , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Fragile X-associated primary ovarian insufficiency (FXPOI), characterized by amenorrhea before age 40 years, occurs in 20% of female FMR1 premutation carriers. Presently, there are no molecular or biomarkers that can help predicting which FMR1 premutation women will develop FXPOI. We previously demonstrated that high FMR4 levels can discriminate between FMR1 premutation carriers with and without FXPOI. In the present study the relationship between the expression levels of FMR4 and the ovarian reserve markers was assessed in female FMR1 premutation carriers under age of 35 years. METHODS: We examined the association between FMR4 transcript levels and the measures of total antral follicle count (AFC) and serum anti-müllerian hormone (AMH) levels as markers of ovarian follicle reserve. RESULTS: Results revealed a negative association between FMR4 levels and AMH (r = 0.45) and AFC (r = 0.64). Statistically significant higher FMR4 transcript levels were found among those FMR1 premutation women with both, low AFCs and AMH levels. CONCLUSIONS: These findings reinforce previous studies supporting the association between high levels of FMR4 and the risk of developing FXPOI in FMR1 premutation carriers.
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Hormônio Antimülleriano , Biomarcadores , Proteína do X Frágil da Deficiência Intelectual , Reserva Ovariana , Insuficiência Ovariana Primária , Humanos , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Reserva Ovariana/genética , Adulto , Biomarcadores/sangue , Hormônio Antimülleriano/sangue , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/sangue , Heterozigoto , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/sangue , Mutação , Folículo Ovariano/metabolismo , Adulto JovemRESUMO
Introduction: A reduction in anti-müllerian hormone (AMH) levels at short-term after bariatric surgery (BS) has been previously described. However, an assessment of ovarian reserve at longer-follow up, and a comprehensive evaluation of the potentially implicated factors has not been reported. Design: Prospective cohort study. Materials and methods: Twenty women aged 18-40 years with BMI 43.95 kg/m2 undergoing BS were studied at baseline (BS0), and at 1 month (BS1), 4 months (BS2), 12 months (BS3), and 24-36 months (BS4) after the surgery. Anthropometrics, reproductive hormones (AMH, FSH, LH, estradiol, testosterone, SHBG, androstenedione), metabolic parameters (adiponectin, leptin, ghrelin, insulin), and nutritional blood parameters (markers of nutritional status, vitamins, and minerals) were obtained at each study time point. Antral follicular count (AFC) was assessed by ultrasonography at BS0, BS3, and BS4. Mixed models were used for analysis of longitudinal data. Results: The mean AMH level was 3.88 ng/mL at BS0, decreased at BS3 (mean= 2.59 ng/mL; p=0.009), and remained stable between BS3 and BS4 (mean= 2.96 ng/mL; p=0.409). We also observed a non-significant decrease in AFC at BS3 (mean=26.14 at BS0, mean 16.81 at BS3; p=0.088) that remained stable at BS4 (mean= 17.86; p=0.731). Mixed models analysis showed: (a) a decrease in 10 kg of body weight was associated with an average decrease of 0.357 ng/mL in AMH (p=0.014); (b) a decrease in 1 BMI point was associated with an average decrease of 0.109 ng/mL in AMH (p=0.005); (c) an increase in 1 µg/mL of adiponectin was associated with an average decrease of 0.091 ng/ml in AMH (p=0.041) Significant positive correlations were found between the AMH levels after BS and plasma concentrations of testosterone, free androgen index, insulin and HOMA index. No significant correlations were detected between AMH levels and nutritional parameters. Conclusions: Our results were in line with previous observations, showing that AMH levels decreased significantly at 12 months after bariatric surgery, in parallel with a non-significant reduction in AFC. Both ovarian reserve markers showed a later stabilization up to the end of the study. Of note, postoperative AMH levels were positively correlated with key androgen and insulin resistance-related parameters.
Assuntos
Cirurgia Bariátrica , Insulinas , Reserva Ovariana , Feminino , Humanos , Adipocinas , Estudos Prospectivos , Adiponectina , Androgênios , Testosterona , Hormônio AntimüllerianoRESUMO
Female FMR1 (Fragile X mental retardation 1) premutation carriers are at risk for developing fragile X-associated primary ovarian insufficiency (FXPOI), a condition characterized by amenorrhea before age 40 years. Not all women with a FMR1 premutation suffer from primary ovarian insufficiency and nowadays there are no molecular or other biomarkers that can help predict the occurrence of FXPOI. Long non-coding RNAs (lncRNAs) comprise a group of regulatory transcripts which have versatile molecular functions, making them important regulators in all aspects of gene expression. In recent medical studies, lncRNAs have been described as potential diagnostic biomarkers in many diseases. The present study was designed to determine the expression profile of three lncRNAs derived from the FMR1 locus, FMR4, FMR5 and FMR6, in female FMR1 premutation carriers in order: (i) to determine a possible role in the pathogenesis of FXPOI and (ii) to investigate whether they could serve as a biomarker for the diagnosis of FXPOI. FMR4, FMR5 and FMR6 transcripts levels were evaluated in total RNA extracted from peripheral blood by digital droplet PCR and compared between FMR1 premutation carriers with FXPOI and without FXPOI. The diagnostic value of lncRNAs was evaluated by receiver operating characteristic (ROC) analysis. Results revealed a significant association between FXPOI and high expression levels of FMR4. No association was obtained for FMR5 or FMR6. ROC curve analysis revealed that FMR4 can distinguish FMR1 premutation carrier with FXPOI with a diagnostic power of 0.67. These findings suggest a potential role of FMR4 as a possible biomarker for FXPOI.
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BACKGROUND: There is limited evidence on the impact of bariatric surgery (BS) on reproductive outcomes in the general population and specifically in patients with polycystic ovarian syndrome (PCOS) or the effect of different BS techniques. PURPOSE: The study aims to investigate the impact of BS on fertility, pregnancy, and newborn outcomes in reproductive age women who have undergone BS and the outcomes according to surgical procedure and PCOS diagnosis. MATERIALS AND METHODS: This was a retrospective, descriptive, cross-sectional study performed in women from 18-39 years undergoing BS in our centre from January 2005 to December 2010. We performed a telephone interview including a structured reproductive health survey on fertility, pregnancy, and offspring outcomes before and after BS. RESULTS: Of the women, 872 underwent BS during the study period, 298 were 18-39 years old, and reproductive data was obtained from 217. Women with regular menstrual cycles increased from 52.9% before BS to 72.9% 1 year after surgery. The percentage of patients with a time-to-pregnancy longer than 12 months was higher after laparoscopic sleeve gastrectomy (LSG) (17.8%) compared to laparoscopic Roux-en-Y gastric bypass (7.1%; p = 0.02). Menstrual regularity was less frequent in PCOS (n = 43) (26.0%) compared to non-PCOS women before BS (60.1%; p = 0.01), with no differences after surgery. Several perinatal results showed an improvement after BS, with a reduction in macrosomia rate and birth weight. CONCLUSION: BS was associated with an improvement in several reproductive outcomes. Menstrual regularity was especially improved in PCOS women. Further research may clarify the impact of LSG on fertility.
Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Síndrome do Ovário Policístico , Adolescente , Adulto , Estudos Transversais , Feminino , Gastrectomia , Humanos , Recém-Nascido , Obesidade Mórbida/cirurgia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/cirurgia , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Studies in macaques have indicated that androgens have some synergistic effects with FSH on folliculogenesis. This study investigated the usefulness of pretreatment with transdermal testosterone in low-responder IVF patients. METHODS: Randomized clinical trial including 62 infertile women who had a background of the first IVF treatment cycle cancelled because of poor follicular response. Patients were randomized in two treatment groups in their second IVF attempt. In patients in Group 1 (n = 31), transdermal application of testosterone preceding standard gonadotrophin ovarian stimulation under pituitary suppression was used. In Group 2 (n = 31 patients), ovarian stimulation was carried out with high-dose gonadotrophin in association with a minidose GnRH agonist protocol. The primary end-point was the incidence of low-responder patients. The main secondary outcome was the incidence of patients reaching ovum retrieval. RESULTS: The percentage of cycles with low response was significantly lower in Group 1 than in Group 2 (32.2 versus 71% 95% confidence interval for the difference, 15.7-61.6; P < 0.05). The number of patients with ovum retrieval tended to be higher in Group 1 than in Group 2 (80.6 versus 58.1% P = 0.09), the difference reaching statistical significance (81.2 versus 41.1%; P < 0.05) when only patients having normal basal FSH levels (16 and 17 patients in Groups 1 and 2, respectively) were considered. CONCLUSIONS: Pretreatment with transdermal testosterone may improve the ovarian sensitivity to FSH and follicular response to gonadotrophin treatment in previous low-responder IVF patients. This approach leads to an increased follicular response compared with a high-dose gonadotrophin and minidose GnRH agonist protocol.
Assuntos
Androgênios/uso terapêutico , Fertilização in vitro , Gonadotropinas/uso terapêutico , Testosterona/uso terapêutico , Administração Cutânea , Adulto , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Gonadotropina Coriônica/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Feminina/diagnóstico por imagem , Infertilidade Feminina/tratamento farmacológico , Hormônio Luteinizante/sangue , Recuperação de Oócitos , Ovário/efeitos dos fármacos , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Resultado do Tratamento , UltrassonografiaRESUMO
OBJECTIVE: Transdermal testosterone has been used in different doses and in different stimulation protocols in poor responders. The aim of the present study is to compare the luteal estradiol/GnRH antagonists protocol versus long GnRH agonists in poor responder patients according to the Bologna criteria, in which transdermal testosterone has been used prior to the stimulation with gonadotropins. METHODS: In this retrospective analysis, a total of 141 poor responder patients according to the Bologna criteria were recruited. All patients were treated with transdermal testosterone preceding ovarian stimulation with gonadotropins during 5 days. In 53 patients we used the conventional antagonist protocol (Group 1). In 88 patients (GrH pituitary suppression was achieved by leuprolide acetate according to the conventional long protocol (Group 2). We analyzed the ovarian stimulation parameters and IVF outcomes. RESULTS: Comparing groups 1 and 2, there were no significant differences between cancellation rates and number of oocytes retrieved. However the total gonadotropin dose used and the mean length of stimulation were significantly lower in group 1 when compared to group 2. There were no significant differences in pregnancy outcomes; however, there was a slight increase in the implantation rate in group 1 vis-a-vis group 2, although statistical significance was not achieved. CONCLUSION: TT in poor responder patients can be effective both with the conventional agonist's long protocol and with the conventional antagonist's protocol. However, short regimes with previous estradiol antagonists in the luteal phase facilitate ovarian stimulation by shortening the days of treatment and the consumption of gonadotropins.
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Estradiol , Hormônio Liberador de Gonadotropina , Hormônios , Indução da Ovulação , Testosterona , Administração Cutânea , Adulto , Estradiol/administração & dosagem , Estradiol/uso terapêutico , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônios/administração & dosagem , Hormônios/uso terapêutico , Humanos , Fase Luteal , Indução da Ovulação/métodos , Indução da Ovulação/estatística & dados numéricos , Gravidez/estatística & dados numéricos , Estudos Retrospectivos , Testosterona/administração & dosagem , Testosterona/uso terapêuticoRESUMO
BACKGROUND: Surgical treatment has modest efficacy for the treatment of infertility associated with early-stage endometriosis. Immunomodulation with pentoxifylline is considered as a new strategy potentially useful in treating endometriosis. Thus, this study investigated the usefulness of combined laparoscopic surgery and pentoxifylline therapy in the treatment of infertility associated with minimal to mild endometriosis. METHODS: A prospective, randomized, controlled blind trial was conducted. Patients entered the study immediately after laparoscopic surgery and were randomly assigned to the treatment with either oral pentoxifylline (800 mg/day) (pentoxifylline group, n = 51) or an oral placebo (placebo group, n = 53). Patients were then observed for pregnancy for 6 months. RESULTS: Among 98 patients finally considered in the evaluation of the results, the 6 month overall pregnancy rates were 28 and 14% in the pentoxifylline and placebo groups, respectively. Thus, an absolute difference of 14% (95% CI -2 to 30) (Chi-squared test, P = 0.1) in the cumulative probability of pregnancy in 6 months after laparoscopic surgery in patients receiving pentoxifylline versus placebo post-operatively was observed. CONCLUSION: Our findings provide preliminary clinical evidence to suggest the new experimental treatment approaches, toward endometriosis, that are based on immunomodulation deserve further attention. Well-designed multicenter trials are warranted to confirm or refute our results.
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Endometriose/terapia , Fatores Imunológicos/uso terapêutico , Infertilidade Feminina/terapia , Pentoxifilina/uso terapêutico , Adulto , Terapia Combinada , Endometriose/complicações , Endometriose/tratamento farmacológico , Endometriose/cirurgia , Feminino , Humanos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Infertilidade Feminina/cirurgia , Laparoscopia , Gravidez , Taxa de GravidezRESUMO
Objectives To examine perinatal outcomes in pregnancies conceived by different methods: fertile women with spontaneous pregnancies, infertile women who achieved pregnancy without treatment, pregnancies achieved by ovulation induction (OI) and in vitro fertilization or intra-cytoplasmic sperm injection (IVF/ICSI). Methods Retrospective single-center cohort study including 200 fertile and 748 infertile women stratified according to infertility treatment. The outcome measurements were preterm delivery (PTD), small-for-gestational-age (SGA), gestational diabetes, placenta previa or preeclampsia. Results The overall rate of pregnancy complications was significantly increased in all infertility groups regardless of the infertility treatment (adjusted odds ratio (OR): infertile without treatment 2.3 versus OI 2.2 versus IVF/ICSI 3.4). While PTD was mainly associated to IVF/ICSI (adjusted OR: infertile without treatment 1.3 versus OI 1.6 versus IVF/ICSI 3.3), SGA was significantly associated to both OI and IVF/ICSI (adjusted OR: infertile without treatment 1.9 versus OI 2.7 versus IVF/ICSI 2.6). All these associations remained statistically significant after adjusting by maternal age and twin pregnancy. Conclusions This study confirms the higher prevalence of pregnancy complications in infertile women irrespectively of receiving infertility treatment or not, and further describes a preferential association of prematurity with IVF/ICSI, and SGA with treated infertility (OI and IVF/ICSI).
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Fertilização in vitro/efeitos adversos , Desenvolvimento Fetal , Infertilidade Feminina/terapia , Indução da Ovulação/efeitos adversos , Complicações na Gravidez/epidemiologia , Adulto , Análise de Variância , Estudos de Casos e Controles , Feminino , Fertilização in vitro/estatística & dados numéricos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Indução da Ovulação/estatística & dados numéricos , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez , Gravidez de Alto Risco , Nascimento Prematuro , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/efeitos adversosRESUMO
OBJECTIVE: To analyze natural cycle IVF (NC-IVF) results according to patient age, ovarian reserve status following the Bologna criteria, cause of infertility, and modification of the cycle with the use of GnRH antagonist. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENT(S): Nine hundred forty-seven natural cycles carried out in 320 patients. INTERVENTION(S): Analysis of 947 NC-IVF outcomes performed in one single center between January 2010 and December 2014. MAIN OUTCOME MEASURE(S): Pregnancy rates per cycle started, per ET, and per patient, as well as ongoing pregnancy rate at a minimum of 12 weeks of gestation. RESULT(S): Among the three age groups analyzed (≤35 years, 36-39 years, and ≥40 years), pregnancy rates per cycle were significantly lower in the older group of patients (11.4% vs. 11.6% vs. 5.9%). In addition, miscarriage rate (7.7% vs. 34.4% vs. 50%) and ongoing pregnancy rate (10.6% vs. 7.6%vs. 3.0%) were negatively affected by patient age. However, no differences were observed according to patient ovarian reserve status, cause of infertility, or modification of the cycle with GnRH antagonist. The multivariate logistic regression confirmed that patient age was the only variable that could predict pregnancy in NC-IVF cycles (odds ratio, 0.93; 95% confidence interval, 0.88-0.98). CONCLUSION(S): NC-IVF is a feasible and "patient-friendly" option to be offered to young patients, independent of their ovarian reserve status.
Assuntos
Fertilização in vitro , Infertilidade Feminina/terapia , Idade Materna , Reserva Ovariana , Ovário/fisiopatologia , Aborto Espontâneo/etiologia , Adulto , Distribuição de Qui-Quadrado , Feminino , Fertilidade , Fármacos para a Fertilidade Feminina/administração & dosagem , Fertilização in vitro/efeitos adversos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/administração & dosagem , Hospitais Universitários , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Modelos Logísticos , Análise Multivariada , Razão de Chances , Reserva Ovariana/efeitos dos fármacos , Ovário/efeitos dos fármacos , Seleção de Pacientes , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Fatores de Risco , Espanha , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
OBJECTIVE: To characterize the chronology of hemodynamic changes in in vitro fertilization (IVF) cycles and its relationship with circulating ovarian steroids, cytokines, and their mediator nitric oxide. DESIGN: Prospective, cross-sectional study. SETTING: University teaching hospital. PATIENT(S): Eighty-eight IVF patients. INTERVENTION(S): Ovarian stimulation with FSH under pituitary suppression. MAIN OUTCOME MEASURE(S): Circulating levels of estradiol, progesterone, nitrite/nitrate, interleukin-6, vascular endothelial growth factor, tumor necrosis factor alpha, aldosterone, norepinephrine, as well as measurements of plasma renin activity and mean arterial pressure. RESULT(S): The maximal stimulation of the renin-aldosterone and sympathetic nervous systems was seen 7 days after hCG administration, although values still remained elevated over normal control values on day of hCG + 11. Mean arterial pressure in IVF patients remained significantly reduced throughout the luteal phase. Changes in the stimulation of the renin-aldosterone system correlated temporally with progesterone but not estradiol levels. No significant changes were observed in circulating concentrations of cytokines investigated or nitric oxide. CONCLUSION(S): The circulatory changes and the homeostatic activation of the renin-aldosterone system and sympathetic nervous system that consistently develop in patients undergoing controlled ovarian hyperstimulation for IVF is a feature associated with the luteinization process. These hemodynamic changes occur in the absence of variations in the circulating levels of cytokines potentially involved in ovarian hyperstimulation syndrome.
Assuntos
Citocinas/sangue , Estradiol/sangue , Fertilização in vitro , Hemodinâmica , Progesterona/sangue , Adulto , Gonadotropina Coriônica/uso terapêutico , Estudos Transversais , Feminino , Humanos , Óxido Nítrico/sangue , Indução da Ovulação/métodos , Estudos Prospectivos , Sistema Renina-Angiotensina , Sistema Nervoso Simpático/fisiopatologiaRESUMO
OBJECTIVE: To compare the safety of recombinant human luteinizing hormone (LH) with that of urinary hCG in terms of the hemodynamic changes when they are used to induce final follicular maturation in patients undergoing in vitro fertilization (IVF). A secondary end point was efficacy in terms of IVF outcome. DESIGN: Prospective, randomized clinical trial. SETTING: University teaching hospital. PATIENT(S): Thirty IVF patients. INTERVENTION(S): Ovarian stimulation was induced with FSH under pituitary suppression. Patients were randomized to receive either hCG or recombinant human LH as a trigger of oocyte maturation (5,000 IU) and for luteal phase support (5,000 IU, 2,500 IU, and 2,500 IU on the day of follicular aspiration, 2 days later, and 5 days later, respectively). MAIN OUTCOME MEASURE(S): Mean arterial pressure, cardiac output, peripheral vascular resistance, and serum levels of progesterone, plasma concentrations of aldosterone, norepinephrine, and plasma renin activity were measured in all patients on postovulatory day 7 of the spontaneous menstrual cycle preceding IVF (baseline) and 7 days after the hCG/recombinant human LH ovulatory injection during the IVF cycle. RESULT(S): Ovarian response and IVF outcome (pregnancy rate, 60%) were similar in both treatment groups. On the seventh day after hCG/recombinant human LH administration, the peripheral vascular resistance was significantly lower and serum progesterone concentrations significantly higher in the hCG group as compared with the recombinant human LH group. The percentage change from baseline values during IVF cycles in all hemodynamic and neurohormonal variables investigated was higher (albeit not statistically different) in the group treated with hCG vs. the group treated with recombinant human LH. CONCLUSION(S): Recombinant human LH is associated with less intense circulatory changes than hCG when it is given to induce final follicular maturation and luteal phase support in IVF procedures.