RESUMO
AIM: To evaluate the overall performance and oocyte quality of follicular phase stimulation (FPS) vs. luteal phase stimulation (LPS) among patients undergoing double ovarian stimulation (DuoStim). MATERIALS AND METHODS: Observational retrospective two-center cohort study including 79 infertile women who underwent a total of 87 DuoStim cycles between January 2017 and May 2019. Besides assessing baseline characteristics in order to determine the patients' clinical profile, we analyzed the FPS and LPS regarding the total dose of gonadotropin received, the duration of stimulation, the number and maturity of oocytes, fertilization and blastocyst formation rates, and the number of blastocysts obtained. RESULTS: The patients' baseline characteristics were compatible with a diminished ovarian reserve and poor reproductive prognosis. While the luteal phase needed longer stimulation (12 days (5-19) vs. 11 (7-16), p < .001) and slightly higher gonadotropin doses (2946 ± 890 IU vs. 2550 ± 970 IU, p < .001), no significant differences were detected in the oocyte maturity, fertilization, and blastocyst formation rates. However, the number of oocytes retrieved (5 (0-16) vs. 4 (0-15), p = .006), mature oocytes (4 (0-15) vs. 3 (0-11), p = .032), and blastocysts obtained (70 vs. 53) were substantially greater after LPS. CONCLUSIONS: The DuoStim strategy in poor prognosis patients increases the number of oocytes and blastocysts available. Moreover, the number of oocytes and blastocysts obtained are higher after LPS when compared to FPS. Thus, it should be considered for selected patients in order to not only improve reproductive outcomes but also shorten the time to pregnancy.
Assuntos
Fase Folicular/fisiologia , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Adulto , Estudos de Coortes , Feminino , Fertilização in vitro/métodos , Fase Folicular/efeitos dos fármacos , Gonadotropinas/farmacologia , Gonadotropinas/uso terapêutico , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/patologia , Fase Luteal/efeitos dos fármacos , Fase Luteal/fisiologia , Recuperação de Oócitos/métodos , Recuperação de Oócitos/normas , Oócitos/efeitos dos fármacos , Oócitos/patologia , Gravidez , Taxa de Gravidez , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
When levonorgestrel (LNG) is given for emergency contraception during the follicular phase, it not only inhibits or delays ovulation, but also induces changes in endometrial secretions that modulate sperm functionality. In order to characterize the female reproductive tract secreted molecules that may affect human spermatozoa, we analyzed changes in the protein content of uterine flushings obtained from women during the periovulatory phase of a control and a LNG-treated menstrual cycle. Lectin affinity analysis and 2D gel electrophoresis of uterine samples showed changes in protein glycosylation patterns and the presence of 31 differentially expressed proteins (8 upregulated and 23 downregulated). Mass spectrometry and Western blot analyses of the differential expressed proteins showed lactotransferrin (LTF) as one of the upregulated molecules by LNG. In this study, LTF exhibited significant dose-related effects on sperm functionality, particularly a decrease of calcium ionophore-induced acrosome reaction and protein tyrosine phosphorylation. Overall, the results indicated that LNG promoted changes in the proteome of uterine secretions that might compromise human sperm capacitation. These data further support the participation of other mechanisms of action of LNG as emergency contraceptive, in addition to those on ovulation.
Assuntos
Contraceptivos Hormonais/uso terapêutico , Fase Folicular/efeitos dos fármacos , Lactoferrina/metabolismo , Lactoferrina/farmacologia , Levanogestrel/uso terapêutico , Espermatozoides/efeitos dos fármacos , Útero/efeitos dos fármacos , Reação Acrossômica/efeitos dos fármacos , Adulto , Ionóforos de Cálcio/farmacologia , Feminino , Fase Folicular/metabolismo , Glicosilação , Humanos , Masculino , Ovulação/efeitos dos fármacos , Fosforilação , Espermatozoides/metabolismo , Tirosina/metabolismo , Útero/metabolismo , Adulto JovemRESUMO
In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.
Assuntos
Regulação da Expressão Gênica , Kisspeptinas/agonistas , Hormônio Luteinizante/metabolismo , Neurônios/metabolismo , Norepinefrina/metabolismo , Área Pré-Óptica/metabolismo , Regulação para Cima , Fatores de Transcrição ARNTL/agonistas , Fatores de Transcrição ARNTL/antagonistas & inibidores , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Animais , Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Feminino , Fase Folicular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Kisspeptinas/antagonistas & inibidores , Kisspeptinas/genética , Kisspeptinas/metabolismo , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Ovariectomia/efeitos adversos , Proteínas Circadianas Period/agonistas , Proteínas Circadianas Period/antagonistas & inibidores , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Prazosina/farmacologia , Área Pré-Óptica/efeitos dos fármacos , Ratos Wistar , Receptores Adrenérgicos alfa 1/química , Receptores Adrenérgicos alfa 1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
The purpose of this study was to investigate the effects of the ovarian hormones and the use of oral contraceptive pills (OCP) on cardiac vagal withdrawal at the onset of dynamic exercise. Thirty physically active women aged 19-32 years were divided into two groups: OCP users (n = 17) and non-OCP users (n = 13). Participants were studied randomly at three different phases of the menstrual cycle: early follicular (day 3.6 ± 1.2; range 1-5), ovulatory (day 14.3 ± 0.8; range 13-16) and midluteal (day 21.3 ± 0.8; range 20-24), according to endogenous (in non-OCP users) or exogenous (in OCP users) estradiol and progesterone variations. The cardiac vagal withdrawal was represented by the cardiac vagal index (CVI), which was obtained by the 4-s exercise test. Additionally, resting heart rate, systolic (SBP) and diastolic blood pressure (DBP) were obtained. The CVI was not significantly different between the three phases of the menstrual cycle in either the non-OCP users (early follicular: 1.58 ± 0.1; ovulatory: 1.56 ± 0.1; midluteal: 1.58 ± 0.1, P > 0.05) or OCP users (early follicular: 1.47 ± 0.1; ovulatory: 1.49 ± 0.1; midluteal: 1.47 ± 0.1, P > 0.05) (mean ± SEM). Resting cardiovascular responses were not affected by hormonal phase or OCP use, except that the SBP was higher in the OCP users than non-OCP users in all phases of the cycle (P < 0.05). In summary, our results demonstrate that cardiac vagal withdrawal at the onset of dynamic exercise was not impacted by the menstrual cycle or OCP use in physically active women.
Assuntos
Anticoncepcionais Orais/farmacologia , Exercício Físico , Coração/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Anticoncepção , Estradiol/sangue , Estradiol/farmacologia , Feminino , Período Fértil/efeitos dos fármacos , Período Fértil/fisiologia , Fase Folicular/efeitos dos fármacos , Fase Folicular/fisiologia , Coração/inervação , Frequência Cardíaca/efeitos dos fármacos , Humanos , Fase Luteal/efeitos dos fármacos , Fase Luteal/fisiologia , Progesterona/sangue , Progesterona/farmacologia , Descanso , Nervo Vago/fisiologiaRESUMO
O Thiodan(r) é um organoclorado a base de endosulfan que pode causar alterações morfológicas nos tecidos de peixes, dependendo da concentração e tempo de exposição. Este estudo teve como objetivo determinar a CL50-96h do Thiodan(r) (endosulfan 350g L-1) para fêmeas de lambaris Astyanax bimaculatus em período de reprodução e analisar a morfologia do desenvolvimento folicular em diferentes concentrações do agrotóxico. Foram feitos quatro experimentos: 1) sem aclimatação e sem alimentação; 2) sem aclimatação e alimentados; 3) com aclimatação de 10 dias e sem alimentação; 4) com aclimatação de 10 dias e alimentados. A CL50-96h determinada foi de 13,6µg L-1, com intervalo de confiança de 10,1 a 18,4µg L-1 (P 0,05). Em todos os experimentos, foram utilizadas três concentrações diferentes do Thiodan(r) inferiores à CL50-96h pré-determinada em laboratório de acordo com a NBR 15088 (ABNT, 2007). Os lambaris foram expostos ao Thiodan(r) por 96 horas em três concentrações subletais de 1,15; 2,3 e 5,6µg L-1 e um grupo controle, livre de agrotóxico. Morfologicamente, percebeu-se que a ação do Thiodan(r) nas concentrações subletais não alterou a morfologia do desenvolvimento folicular. Porém, o diâmetro folicular nos folículos secundários no experimento com aclimatação/com alimentação expostos ao Thiodan(r) foi maior em relação ao grupo controle (P 0,05). Esses dados sugerem que a reprodução pode ser afetada pelo produto químico e pode causar comprometimento no desenvolvimento folicular.(AU)
Thiodan(r) is an organochlorine based in endosulfan which can cause morphological changes in fish tissues exposed to it depending on the concentration and exposure time. This study aimed to determine the LC50-96h of Thiodan(r) (350g L-1 endosulfan) for lambaris females of Astyanax bimaculatus in a reproduction period and analyze the morphology of follicular development in different experiments. Four experiments were performed: without adaptation and no feeding, feeding without adaptation, with adaptation and without feeding, with adaptation and feeding. The LC50-96h determined was 13.6µg L-1, with a confidence interval from 10.1 to 18.4µg L-1 (P 0.05). The lambaris were exposed to Thiodan(r) for 96 hours in three sub-lethal concentrations of 1.15, 2.3 and 5.6µg L-1 and without pesticides control group. Morphologically, it was noted that the action of Thiodan(r) in sub-lethal concentrations did not alter the morphology of follicular development. However, the follicular diameter in secondary follicles in the experiment with adaptation and feeding exposed to Thiodan(r) was higher relative to the control group (P 0.05). These data suggest that reproduction may be affected by chemical and can cause impairment in the follicular development.(AU)
Assuntos
Animais , Feminino , Inseticidas/administração & dosagem , Peixes , Fase Folicular/efeitos dos fármacos , Reprodução/efeitos dos fármacosRESUMO
BACKGROUND: During controlled ovarian hyperstimulation (COH) follicle-stimulating hormone (FSH) is frequently used for several days to achieve follicular development. FSH is a relatively expensive drug, substantially contributing to the total expenses of assisted reproductive techniques (ART). When follicles achieve a diameter greater than 10 mm they start expressing luteinising hormone (LH) receptors. At this point, FSH might be replaced by low-dose human chorionic gonadotropin (hCG), which is less expensive. In addition to cost reduction, replacing FSH by low-dose hCG has a theoretical potential to reduce the incidence of ovarian hyperstimulation syndrome (OHSS). OBJECTIVES: To evaluate the effectiveness and safety of using low-dose hCG to replace FSH during the late follicular phase in women undergoing COH for assisted reproduction, compared to the use of a conventional COH protocol. SEARCH METHODS: We searched for randomised controlled trials (RCT) in electronic databases (Menstrual Disorders and Subfertility Group Specialized Register, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (ISI Web of knowledge), and grey literature (OpenGrey); additionally we handsearched the reference list of included studies and similar reviews. The last electronic search was performed in February 2013.. SELECTION CRITERIA: Only true RCTs comparing the replacement of FSH by low-dose hCG during late follicular phase of COH were considered eligible; quasi or pseudo-randomised trials were not included. Cross-over trials would be included only if data regarding the first treatment of each participant were available; trials that included the same participant more than once would be included only if each participant was always allocated to the same intervention and follow-up periods were the same in both/all arms, or if data regarding the first treatment of each participant were available. We excluded trials that sustained FSH after starting low-dose hCG and those that started FSH and low-dose hCG at the same time. DATA COLLECTION AND ANALYSIS: Study eligibility, data extraction, and assessment of the risk of bias were performed independently by two review authors, and disagreements were solved by consulting a third review author. We corresponded with study investigators in order to solve any query, as required. The overall quality of the evidence was assessed in a GRADE summary of findings table. MAIN RESULTS: The search retrieved 1585 records; from those five studies were eligible, including 351 women (intervention = 166; control = 185). All studies were judged to be at high risk of bias. All reported per-woman rather than per-cycle data.When use of low-dose hCG to replace FSH was compared with conventional COH for the outcome of live birth, confidence intervals were very wide and findings were compatible with appreciable benefit, no effect or appreciable harm for the intervention (RR 1.56, 95% CI 0.75 to 3.25, 2 studies, 130 women, I² = 0%, very-low-quality evidence). This suggests that for women with a 14% chance of achieving live birth using conventional COH, the chance of achieving live birth using low-dose hCG would be between 10% and 45%.Similarly confidence intervals were very wide for the outcome of OHSS and findings were compatible with benefit, no effect or harm for the intervention (OR 0.30, 95% CI 0.06 to 1.59, 5 studies, 351 women, I² = 59%, very-low-quality evidence). This suggests that for women with a 3% risk of OHSS using conventional COH, the risk using low-dose hCG would be between 0% and 4%.The confidence intervals were wide for the outcome of ongoing pregnancy and findings were compatible with benefit or no effect for the intervention (RR 1.14, 95% CI 0.81 to 1.60, 3 studies, 252 women, I² = 0%, low-quality evidence). This suggests that for women with a 32% chance of achieving ongoing pregnancy using conventional COH, the chance using low-dose hCG would be between 27% and 53%.The confidence intervals were wide for the outcome of clinical pregnancy and findings were compatible with benefit or no effect for the intervention (RR 1.19, 95% CI 0.92 to 1.55, 5 studies, 351 women, I² = 0%, low-quality evidence). This suggests that for women with a 35% chance of achieving clinical pregnancy using conventional COH, the chance using low-dose hCG would be between 32% and 54%.The confidence intervals were very wide for the outcome of miscarriage and findings were compatible with benefit, no effect or harm for the intervention (RR 1.08, 95% CI 0.50 to 2.31, 3 studies, 127 pregnant women, I² = 0%, very-low-quality evidence). This suggests that for pregnant women with a 16% risk of miscarriage using conventional COH, the risk using low-dose hCG would be between 8% and 36%.The findings for the outcome of FSH consumption were compatible with benefit for the intervention (MD -639 IU, 95% CI -893 to -385, 5 studies, 333 women, I² = 88%, moderate-quality evidence).The findings for the outcome of number of oocytes retrieved were compatible with no effect for the intervention (MD -0.12 oocytes, 95% CI -1.0 to 0.8 oocytes, 5 studies, 351 women, I² = 0%, moderate-quality evidence). AUTHORS' CONCLUSIONS: We are very uncertain of the effect on live birth, OHSS and miscarriage of using low-dose hCG to replace FSH during the late follicular phase of COH in women undergoing ART, compared to the use of conventional COH. The current evidence suggests that this intervention does not reduce the chance of ongoing and clinical pregnancy; and that it is likely to result in an equivalent number of oocytes retrieved expending less FSH. More studies are needed to strengthen the evidence regarding the effect of this intervention on important reproductive outcomes.
Assuntos
Gonadotropina Coriônica/administração & dosagem , Substituição de Medicamentos , Fármacos para a Fertilidade Feminina/administração & dosagem , Hormônio Foliculoestimulante/administração & dosagem , Fase Folicular/efeitos dos fármacos , Técnicas de Reprodução Assistida , Aborto Espontâneo/epidemiologia , Gonadotropina Coriônica/efeitos adversos , Intervalos de Confiança , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Fase Folicular/fisiologia , Humanos , Nascido Vivo , Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The purpose of the study was to determine if the effect of llama OIF on LH secretion is mediated by stimulation of the hypothalamus or pituitary gland. METHODS: Using a 2-by-2 factorial design to examine the effects of OIF vs GnRH with or without a GnRH antagonist, llamas with a growing ovarian follicle greater than or equal to 8 mm were assigned randomly to four groups (n = 7 per group) and a) pre-treated with 1.5 mg of GnRH antagonist (cetrorelix acetate) followed by 1 mg of purified llama OIF, b) pre-treated with 1.5 mg of cetrorelix followed by 50 micrograms of GnRH, c) pre-treated with a placebo (2 ml of saline) followed by 1 mg of purified llama OIF or d) pre-treated with a placebo (2 ml of saline) followed by 50 micrograms of GnRH. Pre-treatment with cetrorelix or saline was given as a single slow intravenous dose 2 hours before intramuscular administration of either GnRH or OIF. Blood samples for LH measurement were taken every 15 minutes from 1.5 hours before to 8 hours after treatment. The ovaries were examined by ultrasonography to detect ovulation and CL formation. Blood samples for progesterone measurement were taken every-other-day from Day 0 (day of treatment) to Day 16. RESULTS: Ovulation rate was not different (P = 0.89) between placebo+GnRH (86%) and placebo+OIF groups (100%); however, no ovulations were detected in llamas pre-treated with cetrorelix. Plasma LH concentrations surged (P < 0.01) after treatment in both placebo+OIF and placebo+GnRH groups, but not in the cetrorelix groups. Maximum plasma LH concentrations and CL diameter profiles did not differ between the placebo-treated groups, but plasma progesterone concentrations were higher (P < 0.05), on days 6, 8 and 12 after treatment, in the OIF- vs GnRH-treated group. CONCLUSION: Cetrorelix (GnRH antagonist) inhibited the preovulatory LH surge induced by OIF in llamas suggesting that LH secretion is modulated by a direct or indirect effect of OIF on GnRH neurons in the hypothalamus.
Assuntos
Camelídeos Americanos , Fase Folicular/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Luteinizante/metabolismo , Ovulação/efeitos dos fármacos , Animais , Camelídeos Americanos/sangue , Camelídeos Americanos/metabolismo , Camelídeos Americanos/fisiologia , Regulação para Baixo/efeitos dos fármacos , Feminino , Fármacos para a Fertilidade/metabolismo , Fármacos para a Fertilidade/farmacologia , Fase Folicular/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/farmacologia , Hormônio Luteinizante/sangue , Masculino , Indução da Ovulação/métodos , Placebos , Fluxo Pulsátil/efeitos dos fármacos , Sêmen/metabolismo , Sêmen/fisiologia , Proteínas de Plasma Seminal/metabolismo , Proteínas de Plasma Seminal/farmacologiaRESUMO
BACKGROUND: Current methods of hormonal emergency contraception (EC) are ineffective in preventing follicular rupture when administered in the advanced pre-ovulatory phase. This study was designed to determine the capacity of ulipristal acetate (UPA), a selective progesterone receptor modulator developed for EC, to block follicular rupture when administered with a follicle of >or=18 mm. METHODS: This was a double-blind, crossover, randomized, placebo-controlled study. Thirty-five women contributed with UPA (30 mg. oral) and a placebo cycle. Serial blood sampling for luteinizing hormone (LH), estradiol and progesterone measurements and follicular monitoring by ultrasound were performed before and for 5 days following treatment. Follicular rupture inhibition was assessed in the overall study population and in subgroups of women stratified by when treatment was administered in relation to LH levels (before the onset of the LH surge, after the onset of the surge but before the LH peak or after the LH peak). RESULTS: Follicular rupture failed to occur for at least 5 days following UPA administration in 20/34 cycles [59%; 95% confidence interval (CI) (40.7-75.4%)], whereas rupture took place in all cycles within 5 days of placebo intake. When UPA was administered before the onset of the LH surge, or after the onset but before the LH peak, follicle rupture had not occurred within 5 days in 8/8 (100%) and 11/14 [78.6%; 95% CI (49.2-95.3)] cycles, respectively. In contrast, when UPA was given after the LH peak, follicle rupture inhibition was only observed in 1/12 [8.3%; 95% CI (0.2-38.5)] cycles. CONCLUSIONS: This study demonstrates that UPA can significantly delay follicular rupture when given immediately before ovulation. This new generation EC compound could possibly prevent pregnancy when administered in the advanced follicular phase, even if LH levels have already begun to rise, a time when levonorgestrel EC is no longer effective in inhibiting ovulation.
Assuntos
Anticoncepção Pós-Coito/métodos , Anticoncepcionais Sintéticos Pós-Coito/uso terapêutico , Fase Folicular/efeitos dos fármacos , Norpregnadienos/administração & dosagem , Norpregnadienos/uso terapêutico , Folículo Ovariano/efeitos dos fármacos , Inibição da Ovulação/efeitos dos fármacos , Adulto , Anticoncepção Pós-Coito/efeitos adversos , Anticoncepcionais Sintéticos Pós-Coito/administração & dosagem , Anticoncepcionais Sintéticos Pós-Coito/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Estradiol/sangue , Feminino , Fase Folicular/sangue , Humanos , Hormônio Luteinizante/sangue , Norpregnadienos/efeitos adversos , Tamanho do Órgão , Folículo Ovariano/anatomia & histologia , Folículo Ovariano/diagnóstico por imagem , Progesterona/sangue , Receptores de Progesterona/antagonistas & inibidores , Estatística como Assunto , Fatores de Tempo , Ultrassonografia , Adulto JovemRESUMO
The objective of this retrospective cohort study was to assess the potential effects of preconceptional short-term exposure to particulate air pollution in a real-world situation on pregnancy outcome in infertile women evaluating the possible role of IVF/embryo transfer treatment on this outcome using women who had conceived naturally for the first time during the same time frame as a matched control group. The study provides evidence for an association between brief exposure to high levels of ambient particulate matter (aerodynamic diameter Assuntos
Aborto Espontâneo/etiologia
, Transferência Embrionária
, Fertilização in vitro
, Fase Folicular/efeitos dos fármacos
, Infertilidade Feminina/terapia
, Exposição por Inalação
, Material Particulado/efeitos adversos
, Monitoramento Ambiental
, Feminino
, Humanos
, Infertilidade Feminina/fisiopatologia
, Modelos Logísticos
, Masculino
, Razão de Chances
, Tamanho da Partícula
, Gravidez
, Estudos Retrospectivos
, Medição de Risco
, Fatores de Risco
, Estações do Ano
, Fatores de Tempo
, Resultado do Tratamento
RESUMO
BACKGROUND: There is evidence that cyclooxygenase-2 (COX-2) inhibitors can prevent or delay follicular rupture. COX-2 inhibitors, such as meloxicam, may offer advantages over emergency contraception with levonorgestrel, such as extending the therapeutic window for up to 24 h. We assessed the effect of meloxicam administered in the late follicular phase upon ovulation in women. MATERIALS AND METHODS: This was a single center, double blind, crossover study designed to assess the effects in 27 eligible women (18-40 years old, surgically sterilized with regular menstrual cycles) of meloxicam, 15 or 30 mg/day, administered orally for five consecutive days during the late follicular phase, starting when the leading follicle reached 18 mm diameter. Volunteers underwent two treatment cycles separated by one resting cycle, with randomization to dose sequence. Main outcomes were follicular rupture; serum LH, progesterone and estradiol (E2) levels; and incidence of adverse events. RESULTS: Twenty-two volunteers completed the study. There were no differences between meloxicam doses in menstrual cycle length. Dysfunctional ovulation was observed in 11/22 (50%) cycles treated with 15 mg/day and 20/22 (90.9%) cycles with 30 mg/day (P = 0.0068). All women had normal luteal phase progesterone levels; mean maximal values +/- SEM were 42 +/- 4.1 and 46.8 +/- 2.6 nmol/l for 15 and 30 mg/day groups, respectively. There were no serious adverse events, and no changes in LH and E2 levels or in cycle length. CONCLUSIONS: Meloxicam 30 mg given for five consecutive days in the late follicular phase is safe, effective and may be an alternative form of emergency contraception.