DuoStim cycles potentially boost reproductive outcomes in poor prognosis patients.

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.

Proteomic changes in uterine flushings after levonorgestrel treatment and effects on sperm function.

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.

The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input.

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.

Effects of ovarian hormones and oral contraceptive pills on cardiac vagal withdrawal at the onset of dynamic exercise.

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.

O inseticida Thiodan® sobre o desenvolvimento folicular de lambaris / Thiodan® insecticide on the follicular development of lambaris

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)

FSH replaced by low-dose hCG in the late follicular phase versus continued FSH for assisted reproductive techniques.

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.

Cetrorelix suppresses the preovulatory LH surge and ovulation induced by ovulation-inducing factor (OIF) present in llama seminal plasma.

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.

Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture.

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.

Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: potential for emergency contraception.

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.

Effects of exposure to high levels of particulate air pollution during the follicular phase of the conception cycle on pregnancy outcome in couples undergoing in vitro fertilization and embryo transfer.

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

Controlled ovarian stimulation with exclusive FSH followed by stimulation with hCG alone, FSH alone or hMG.

OBJECTIVE: To assess if low-dose hCG is similar to hMG and to rFSH in the late follicular phase. STUDY DESIGN: In a prospective randomized controlled trial, 51 patients undergoing controlled ovarian stimulation received ovarian priming with rFSH and then received hCG (200 IU/day) (hCG group, n=17), hMG (225 IU/day) (hMG group, n=17) or rFSH (200 IU/day) (FSH group, n=17) in the late stage of follicular development. Parameters of follicular response and serum estradiol, progesterone and testosterone levels were assessed. RESULTS: Pre-ovulatory ovarian follicle occurrence and length of treatment were similar among the three treatment groups. Serum progesterone level on the day of pre-ovulatory hCG was significantly higher in the hCG group than in the hMG or rFSH group. Clinical pregnancy rates were similar for all groups. The total cost of treatment was significantly lower for the hCG group than for the groups supplemented with hMG or rFSH. CONCLUSIONS: LH in the form of low-dose hCG during the late follicular phase induced the same follicular pattern as hMG and rFSH after ovulation induction. The procedure using hCG produced pregnancy rates similar to those obtained using hMG and rFSH, even though the patients showed higher serum progesterone levels on the hCG day.

Caprine luteinizing hormone isoforms during the follicular phase and anestrus.

The relative proportion of the circulating luteinizing hormone isoforms in goats during follicular phase (pre-ovulatory peak; F) and anestrus (A) was investigated. Estrus was synchronized in six goats with a prostaglandin analogue. After estrus was detected, blood samples were taken at 1 h intervals for 24 h. Four anestrous goats received 100 microg i.v. of GnRH and blood samples were collected every 15 min for 5 h. Samples with the greatest LH concentration in follicular phase and after GnRH administration (anestrus) were analyzed by chromatofocusing and eluted with a pH gradient from 10.5 to 3.5. For quantification purposes eluted LH was grouped into basic (pH> or =7.5), neutral (pH 7.4-6.5) and acidic isoforms (pH< or =6.4) as well as by pH unit. In both physiological conditions (PC), basic and acidic isoforms were greater than the neutral. With this grouping criteria, there was an interaction between PC and pH group, with the proportion of neutral isoforms being greater (p<0.05) in A (12.0+/-0.8%) as compared with F (5+/-2%). Analysis by pH unit showed a very basic group of eluted isoforms (pH> or =10), which amounted to a percentage of 6.0+/-0.4% of the total observed during A, and 3+/-1% during F (p<0.05). Predominant isoforms in A eluted in the pH range 9.99-9.0 (42+/-3%) as compared to 7+/-3% (p<0.01) in that pH range in F. In contrast, the predominant isoforms in F eluted in the pH range 8.99-8.0, representing 55+/-8%, while in A the proportion was 11+/-2% (p<0.01). Isoforms eluted at the pH range 7.9-7 represented a significantly greater proportion during A (5.0+/-0.6%) as compared with F (3+/-1%). This is the first report on goat LH circulating isoforms. During A the LH isoforms secreted by the pituitary are more basic than during F.

Ovarian stimulation with daily late follicular phase administration of low-dose human chorionic gonadotropin for in vitro fertilization: a prospective, randomized trial.

OBJECTIVE: Evaluate the effectiveness of a new ovarian stimulation (OS) protocol before IVF. DESIGN: Prospective clinical randomized trial. SETTING: Private centers. PATIENT(S): Three hundred and twenty-three intended-to-treat women candidates for IVF. INTERVENTION(S): Patients were divided into three groups and administered the following treatments: group A, recombinant hFSH from day 3 until follicles reached 13-14 mm, when recombinant hFSH was lowered to 75 IU daily and daily injections of 200 IU of hCG and a GnRH antagonist were administered until final maturation; group B, recombinant hFSH and a GnRH antagonist; group C, recombinant hFSH and a GnRH agonist. MAIN OUTCOME MEASURE(S): Primary outcome was the number of mature oocytes. Secondary outcomes included average initial and total recombinant hFSH dosage, serum E2 level on day of ovulation, number of oocytes retrieved, fertilization, number of top-quality embryos, endometrial thickness, implantation rate, pregnancy rate (PR), and incidence of ovarian hyperstimulation syndrome (OHSS). RESULT(S): The numbers of oocytes retrieved, mature oocytes, fertilization, top-quality embryos, and embryos transferred were comparable in all groups. Implantation rate, PR, and incidence of OHSS were also comparable. The total dose of recombinant hFSH was significantly lower in group A (1,674.7 +/- 59.4 IU, vs. 2,197.9 +/- 77.8 IU in group B and 2,156.7 +/- 80.9 IU in group C). CONCLUSION(S): This new OS protocol permits follicles and oocytes to fully develop, helps generate top-quality embryos, avoids premature ovulation, establishes clinical pregnancies, reduces administration of recombinant hFSH, minimizes costs, and does not increase the chances of OHSS.

Late follicular phase administration of levonorgestrel as an emergency contraceptive changes the secretory pattern of glycodelin in serum and endometrium during the luteal phase of the menstrual cycle.

This study examined serum glycodelin concentrations and endometrial expression during the luteal phase following oral administration of levonorgestrel (LNG) at different stages of the ovarian cycle. Thirty women were recruited and allocated into three groups. All groups were studied during two consecutive cycles, a control cycle and the treatment cycle. In the treatment cycle, each woman received two doses of 0.75 mg LNG taken 12 h apart on days 3-4 before the luteinizing hormone (LH) surge (Group 1), at the time of LH rise (Group 2) and 48 h after the rise in LH was detected (Group 3). Serum progesterone (P) and glycodelin were measured daily during the luteal phase, and an endometrial biopsy was taken at day LH +9 for immunohistochemical glycodelin-A staining. In Group 1, serum P levels were significantly lower, serum glycodelin levels rose earlier and endometrial glycodelin-A expression was weaker than in Groups 2 and 3, in which no differences were found between control and treatment cycles. Levonorgestrel taken for emergency contraception (EC) prior to the LH surge alters the luteal phase secretory pattern of glycodelin in serum and endometrium. Based on the potent gamete adhesion inhibitory activity of glycodelin-A, the results may account for the action of LNG in EC in those women who take LNG before the LH surge.

Experiencia en inducción de ovulación con factor liberador de gonadotrofinas (GnRH) en pacientes con amenorrea hipotalámica / Experience in ovulation induction with gonadotropin releasing factor (GnRH) in patients with hipotalamic amenorrhea

Presentamos nuestra experiencia en inducción de ovulación y fertilidad en pacientes con amenorrea hipotalámica (AH) tratadas con Hormona liberadora de gonadotrofina (GNRH) en infusión pulsátil (GnRHp). Se trataron 13 pacientes ciomifeno negativo, de las cuales 10 tenían una AH primaria y 3 una AH secundaria. Ocho del total de las pacientes estaban interesadas en fertilidad. El tratamiento se realizó en forma ambulatorio con bomba de infusión pulsátil (ZykiomatO Alemania) programada para administrar 5 Wg de GNRH cada 90 minutos por vía endovenosa. El desarrollo folicular fue monitorizado mediante ultrasonografía y determinaciones hormonales seriadas. Se indujeron un total de 19 ciclos, 14 fueron ovulatorios con folículo único (73,7 por ciento). Trece inducciones se llevaron a cabo en las 8 pacientes expuestas a embarazo, 7 de los cuales fueron concepcionales (tasa de fecundidad: 61,5 por ciento, tasa de embarazo: 85,5 por ciento). Sólo una paciente abortó espontáneamente. No se observaron complicaciones mayores. En conclusión, la inducción de ovulación con GNRH demostró ser un método de inducción de ovulación efectivo y seguro en pacientes con AH ciomifeno resistentes. Debido a que se conservan los mecanismos de retrocontrol entre ovario e hipótesis, los embarazos múltiples y el síndrome de hiperestimulación ovárica son infrecuentes, lo que permite una monitorización menos estricta de la paciente

Pode uma dose única de análogo do GnRH no primeiro dia do ciclo menstrual prevenir o aumento de LH na fase pré-ovulatória? / Can a single dose of the GnRH analogue on the first day of the menstrual period prevent the increase of LH in the preovulatory phase?

Neste estudo foi avaliada a hipótese pela qual uma única dose de análogo do GnRH no primeiro dia do ciclo menstrual preveniria o aumento do hormônio luteinizante (LH) na fase pré-ovulatória de um ciclo estimulado com gonadotrofina menopausal humana (hMG). Um total de 27 pacientes foi dividido em dois grupos. O grupo I (n=9) recebeu uma única dose de 4,0 mg de acetato de leuprolide no primeiro dia do ciclo menstrual. A estimulaçao ovariana foi realizada com hMG na dose de 150 UI no terceiro, quinto, setimo e nono dia do ciclo menstrual. Iniciou-se a monitorizaçao ultra-sonográfica do desenvolvimento folicular no décimo dia do ciclo. O grupo II (n= 18) foi submetido ao mesmo protocolo que o grupo I, com exceçao do análogo do GnRH que nao foi administrado. As doses de gonadotrofinas foram aumentadas em ambos os grupos até a observaçao de pelo menos um folículo > l7mm, quando uma amostra de sangue foi coletada para dosagem de LH, e a gonadotrofina coriônica humana foi administrada na dose de 10.000 UI. Os níveis plasmáticos de LH foram significativamente menores (p

Effect of the antiprogestin onapristone on follicular growth in women.

The effects of the antiprogestin onapristone on the menstrual cycle were assessed in surgically sterilized volunteer women. The steroid was given orally at the dose of 5, 15 or 50 mg/day, from day 5 to day 11 of the cycle. Ovarian ultrasonography and hormonal determinations in plasma and urine were used to monitor the pre-treatment, treated and post-treatment cycles. Onapristone, given at a dose of 5 mg/day, affected follicular growth inconsistently. The dose of 15 or 50 mg/day arrested follicular growth and oestradiol increase and delayed gonadotrophin surge, extending the length of the follicular phase in five of seven women in each group. After discontinuation of treatment the leading follicle resumed its growth and ovulation occurred as judged by the elevation of plasma progesterone, preceded in most but not all cases by an echographic image of follicular collapse. The ensuing luteal phases were not significantly altered in length or plasma progesterone concentration. Cortisol concentrations were unaffected and no serious side-effects were recorded. The antifolliculotrophic effect of onapristone demonstrated here, together with previous reports of similar activity of mifepristone in women, indicate that this may be a general property of compounds that interfere with progesterone receptor function.

Perfil de crecimiento folicular y endometrial en ciclos estimulados con citrato de clomifeno / Follicular and endometrial growth profile in stimulated cycles with clomiphene citrate

Con el objeto de estudiar los patrones de desarrollo folicular y endometrial en ciclos estimulados con citrato de clomifeno (CC), se evaluaron seriadamente 50 ciclos inducidos con CC en 31 mujeres infértiles con trompas permeables. Como grupo control se estudiaron 17 ciclos concepcionales espontáneos en mujeres fértiles. El perfil de crecimiento folicular fue comparable entre ambos grupos hasta el día previo a la ovulación, en que los folículos estimulados con CC alcanzaron un diámetro mayor que los ciclos espontáneos; 23,8 ñ 3,1 mm y 21,6 ñ 2,9 mm respectivamente (p=0,013). la ovulación ocurrió en el día 16,1 ñ 2,9 en los ciclos con CC y en el día 15,1 ñ 1,85 en los ciclos espontáneos (ns). Los anterior sugiere que el folículo con CC debe alcanzar una masa crítica mayor para producir cantidades de estradiol suficientes que reviertan el bloqueo hipotalámico producido por la droga y así desencadenar el peak preovulatorio de LH. El endometrio, bajo la acción de citrato de clomifeno, alcanzó grosores menores que en los ciclos naturales. El endometrio ovulatorio de los ciclos con CC fue de 11,1 ñ 2,02 mm y de 10,6 ñ 1,8 mm en los ciclos espontáneos (ns). Esta observación podría deberse al efecto antiestrogénico directo del CC sobre el endometrio. Se concluye que los ciclos estimulados con CC tienen un patrón de desarrollo folicular y endometrial diferente a los ciclos concepcionales espontáneos

Reserva ovárica funcional en reproducción asistida: dilema clínico / Funtional ovarian reserve in assisted reproduction: a clinical dilema

La respuesta a la estimulación ovárica suprafisiológica en Reproducción Asistida (particularmente FIV-TE Y GIFT), suele ser muy heterogénea, a pesar que las pacientes seleccionadad tienen características clínicas y paraclínicas muy homogéneas. Se encontraron diferentecias altamente significativas entre dos grupos de pacientes con características clínicas similares que fueron estimulados con el mismo esquema. Grupo I(respuesta Adecuada = 22 pacientes) y Grupo II (respuesta inadecuada = 13 pacientes), en relación a los niveles séricos basales de FSH (P =0.007) y a la calidad de la respuesta folicular (P = 0.000). Estos resultados suguieren que la calidad de la respuesta a la estimulación ovárica suprafisiológica, puede reflejar una "Reserva ovárica funcional" y que esta puede predecirse parcialmente con los niveles séricos basales de FSH, más acaso la respuesta inadecuada, paradójica hasta cierto punto ¿no representará una falla ovárica o un síndrome de ovario resistente incipiente o transitorio durante la edad reproductiva?.

[Correlation between estradiol concentrations and follicular measurements vs. oocyte maturity in three different ovarian stimulation schedules]. / Correlación de las concentraciones de estradiol y diámetro folicular con la madurez del ovocito en tres distintos esquemas de estimulación ovárica.

The responses to different ovarian stimulation schedules were studied in women which underwent in programs of assisted fertilization. The follicular development and seric estradiol with the number and quality of the retrieved oocytes. Were correlated 49 patients and divided in 3 groups according to ovarian stimulation schedule were analyzed. The stimulation was followed day by day with seric estradiol and ultrasound follicular measurement. With the three schedules were retrieved 205 oocytes, being mature 179, immature 9 and 17 atretic, there was no significant difference between the different schedules.