Oral Estradiol Valerate Research Articles

Effect of Intrauterine Instillation of Granulocyte Colony-stimulating Factor on Endometrial Thickness and Clinical Pregnancy Rate in Women undergoing in vitro Fertilization Cycles: An Observational Cohort Study

ABSTRACTIntroductionIn spite of significant advances in the field of reproductive medicine, repeated implantation failure (RIF) is a challenging and extremely disappointing problem. The success ofin vitrofertilization and embryo transfer (IVF-ET) cycles depends mainly on uterine receptivity and embryo quality. Successful evaluation of endometrial receptivity conducive to embryo implantation continues to be a challenge in assisted reproductive technology (ART). Several researcher groups have reported the successful use of granulocyte-colony stimulating factor (G-CSF) during IVF cycles in terms of achieving higher clinical pregnancy rates on account of increased endometrial thickness. Women who fail to achieve adequate endometrial thickness despite conventional treatment with high dose estrogen or those with a history of repeated implantation failures in spite of normal endometrial thickness often do not achieve pregnancy and resort to gestational surrogacy. A new therapeutic approach to achieve successful pregnancy in such patients would be very desirable.Study objectivesTo assess the efficacy of a single dose of intrauterine G-CSF on endometrial thickness, implantation and clinical pregnancy rates in women who either had a thin endometrium after estrogen priming (< 8 mm) or a history of repeated implantation failures at IVF, undergoing embryo transfer after 10 days of priming with oral estradiol and vaginal slidenafil.Materials and methodsTwo hundred and thirty-one women (between 24 and 46 years of age) undergoing IVF-ET were recruited for the study. All cases were prospectively studied at the Mumbai Fertility Clinic and IVF Center (a subdivision of Kamala Polyclinic and Nursing Home) over a period of 6 months from January to June 2014, after their written informed consent. Subgroup I consisted of 117 patients who had a persistently thin endometrium (< 8 mm) in spite of high dose oral estradiol valerate and vaginal sildenafil priming. Subgroup II consisted of 114 patients who had a history of repeated (two or more) implantation failures (RIF) at IVF-ET cycles despite adequate endometrium (≥8 mm). All were infused with a single dose of G-CSF (300 mcg) in the uterine cavity after 10 days of priming with oral estradiol valerate and vaginal sildenafil citrate. Endometrial thickness was reassessed 4 days after G-CSF instillation. This was followed by administration of intramuscular progesterone in oil (100 mg) daily with embryo transfer on day 5 of progesterone for all patients. All embryo transfers for patients undergoing oocyte donation or embryo donation were done at the 4-cell stage on day 2. All Frozen embryo transfers (FET) of vitrified embryos were at 8 cell stage. Estimation of serum beta hCG was at 14 days post-embryo transfer for all patients. Successful implantation and net clinical pregnancy rate was confirmed based on appearance of gestational sac on sonogram after 10 days and observation of fetal cardiac activity after 20 days of positive β-hCG results.ResultsOut of total 231 patients recruited in the study, 95% patients from subgroup I (n = 111) and 94% patients from subgroup II (n = 107) showed mean increase in endometrial thickness by at least 2.5 mm within 4 days of G-CSF single dose instillation. A total of 218 patients from both subgroups underwent S. β-hCG estimation 14 days post IVF-ET. Out of 103 β-hCG positive patients, 83 showed net clinical pregnancy (fetal cardiac activity present) giving a net pregnancy rate of 38.07% for the whole study group with 37% in the subgroup with thin endometrium (< 8 mm) and 39.25% in the subgroup with adequate (≥8 mm) endometrium with history of two or more failed implantation at previous IVF-ET cycles. There were no adverse events for the whole study population.ConclusionThere can be a strong possibility with a single dose of 300 mcg intrauterine infusion of G-CSF to achieve significant increase in the endometrial thickness with higher successful pregnancy rate among infertile women under- going IVF-ET cycles with a history of a persistently thin endometrium or repeated implantation failures (rather difficult to treat patients). G-CSF could be a valuable tool to consider before advising the option of surrogacy. In the absence of a control group, our conclusions warrant conduct of further studies.How to cite this articleShah J, Gangadharan A, Shah V. Effect of Intrauterine Instillation of Granulocyte Colony-stimulating Factor on Endometrial Thickness and Clinical Pregnancy Rate in Women undergoingin vitroFertilization Cycles: An Observational Cohort Study. Int J Infertil Fetal Med 2014;5(3):100-106.

Cycle scheduling for in vitro fertilization with oral contraceptive pills versus oral estradiol valerate: a randomized, controlled trial

BackgroundBoth oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate.MethodsBetween January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts) undergoing IVF with the GnRH antagonist protocol were randomized to either the OCP or E2 pretreatment arms, with no restrictions such as blocking or stratification. Authors involved in data collection and analysis were blinded to group assignment. Fifty patients received OCP (30 μg ethinyl E2/150 μg levonorgestrel) for 12–16 days from day 1 or 2, and stimulation was started 5 days after stopping OCP. Similarly, 50 patients received 4 mg/day oral E2 valerate from day 20 for 5–12 days, until the day before starting stimulation.ResultsPretreatment with OCP (mean±SD, 14.5±1.7 days) was significantly longer than with E2 (7.8±1.9 days). Stimulation and embryological characteristics were similar. Ongoing pregnancy rates (46.0% vs. 44.0%; risk difference, –2.0% [95% CI –21.2% to 17.3%]), as well as implantation (43.5% vs. 47.4%), clinical pregnancy (50.0% vs. 48.0%), clinical miscarriage (7.1% vs. 7.7%), and live birth (42.0% vs. 40.0%) rates were comparable between groups.ConclusionsThis is the first study to directly compare these two methods of cycle scheduling in GnRH antagonist cycles. Our results fail to show statistically significant differences in ongoing pregnancy rates between pretreatment with OCP and E2 for IVF with the GnRH antagonist protocol. Although the study is limited by its sample size, our results may contribute to a future meta-analysis. An interesting future direction would be to extend our study to women with decreased ovarian reserve, as these are the patients in whom an increase in oocyte yield—due to the hypothetical beneficial effect of steroid pretreatment on follicular synchronization—could more easily be demonstrated.Trial registrationClinicalTrials.gov http://NCT01501448.

Role of subendometrial autologous stem cell implantation in women with asherman's syndrome

To evaluate the efficacy of sub-endometrial autologous stem cell implantation in women with severe degree of Asherman's Syndrome. (Efficacy is defined as resumption of menstruation). Prospective, Case series. Patients with Asherman's Syndrome (n=6) where other treatment options had failed; bone marrow aspiration was done from iliac crest under local anesthesia .Bone marrow (30 ml) was aspirated using bone marrow aspiration needle (Jamshidi, 11 G). It was collected in heparinised syringes. The Isolation of Mononuclear cells was done by Ficoll density separation method at Stem cell facility.Harvested stem cells were implanted in sub-endometrial zone as identified by transvaginal scan through trans-myometrial route using ovum pick up needle (Cook,17 G) under I.V.sedation.Post implantation patients were given oral Estradiol Valerate (Progynova, Schering manufacturer) 2mg thrice a day for six weeks followed by cyclic Estrogen & progesterone therapy for 3 months(Medroxy-progesterone acetate, Serum Institute of India LTD.) 10 mg once daily from day21- day27. Women were followed up at 3, 6 and 9 month intervals by trans-vaginal ultrasound for the endometrial thickness. Descriptive statistics and statistical analysis of study variables was carried out using STATA version 9.0. Changes in endometrial thickness values due to treatment was compared using ‘t’ –Paired test to see the significant increase in ET values at 3 months, 6 months and 9 months. Mean ±Standard deviation of ET values at 3 months (4.05±1.40), 6 months(5.46±1.36) and 9 months (5.48±1.14) were significantly (P<0.05) increased from pre treatment level (1.38±0.39). The mean (±SD) of MNC counts was 103.3 (±20.45) and ranged from 76 ×10 6 to 128×10 6. Similarly the mean (±SD) of CD34 was 203642 (±269274) and ranged between 10640 and 640090 with median value 58800. Haemopoitic stem cells implantation results in endometrial regeneration in Asherman Syndrome.

Modified luteal support following GnRH-agonist trigger

To demonstrate the use of modified luteal support following GnRh-agonist trigger in patients undergoing IVF/ICSI and at risk of Ovarian Hyper Stimulation Syndrome [OHSS] in preventing early OHSS without compromising pregnancy rate. This prospective, observational study was carried out on 49 patients undergoing IVF/ICSI and at risk of OHSS at Nova IVI Fertility, Ahmedabad from January 2012 to December 2012. The patients aged between 26 and 34 years [average 31 years], underwent stimulation from second day of period with 100 to 300IU of Gonadotropins[average 200IU] using the flexible antagonist protocol. GnRH agonist,[Triptorelin 0.2mg] was given to induce final oocyte maturation in patients at risk of developing OHSS[>20 follicles of >16 mm on the day of trigger].Average estradiol on the day of trigger was 5353+3983 pg/ml. Transvaginal oocyte retrieval[OR]was performed 35hours after the trigger. Luteal phase support was provided in form of vaginal progesterone tablets(200mg 3times/day) and oral estradiol valerate(2mg twice/day)from day after OR. Patients also received 1500 I.U. of recombinant hCG on day of ET. 2embryos were transferred on day3 after OR. An average 22.7+5.6 oocytes were retrieved,76% of which were at metaphaseII. Fertilization rate was 81% and 14+5 embryos were obtained. 2embryos were transferred on day3 in 42 patients and positive hCG rate was 30.9%[13/42] per ET. There was no early OHSS;one patient developed late onset pregnancy induced severe OHSS. Implantation rate was 19%[16/84], rates of miscarriage, ectopic and twins were 7.6%, 15.3%, 23% & ongoing pregnancy rate at 10 weeks was 23.8% [10/42]. GnRH agonists can be used effectively as an alternative to hCG trigger in patients at high risk of OHSS. This delayed administration of hCG provides luteal support& gives time to assess the number & grade of embryos & decide whether the patient should be given hCG & have an ET or should have elective cryopreservation of all embryos.

The use of an oral contraceptive containing estradiol valerate and dienogest before office operative hysteroscopy: a feasibility study

To investigate the impact of a 3 months preoperative administration of an oral contraceptive, containing dienogest (DNG) and estradiol valerate (E2V) on the outcome of office operative hysteroscopy (OOH). One-hundred and forty-two patients diagnosed at office hysteroscopy as having an asynchronous endometrium associated with either a broad-base sessile endometrial polyp (>1.5, <2.5 cm) or a uterine septum (>1/3 uterine cavity) or scheduled for tubal sterilization were enrolled into a prospective case-control study at University “Federico II” of Naples. 86/142 patients accepted the preoperative hormonal treatment (Group A), while 56/142 refused, thus becoming controls (Group B). Group A underwent OOH during the 10th–20th days of the third cycle of treatment. In Group B OOH was performed at enrolment, together with the diagnostic procedure. The study outcomes were: endometrial pattern, success rate, operating time, degree of surgical difficulty and pain score. An overall improvement of the endometrium was reported in 100% of cases in Group A. A statistically significant difference in success rate could not be demonstrated between two groups. Operative procedures were performed significantly quicker and easier in Group A than Group B (p < 0.001 and p < 0.05, respectively). The mean Visual Analog Scale (VAS) score was significantly lower in Group A (p < 0.001). A short pretreatment with combined oral contraceptive (COC) containing E2V/DNG seems to have a favorable impact on endometrium which in turn may result in an improvement of the overall outcomes of OOH.

Effect of estrogen priming through luteal phase and stimulation phase in poor responders in in-vitro fertilization

To verify whether a novel protocol administering E(2) during the luteal phase of the preceding cycle and during ovarian stimulation in GnRH antagonist cycle could enhance follicular response and hence improve outcomes in poor responders. In this retrospective analysis, a total of 155 poor responder patients subjected to IVF/ICSI were analyzed. All the patients had history of more than one prior IVF cycle failure with poor response (less than 5 oocytes retrieved and/or maximal E₂ level less than 500 pg/mL) by using conventional long agonist or antagonist protocol. In luteal E2 treatment protocol (n = 86), oral estradiol valerate 4 mg/day was initiated on luteal day 21 and either stopped at menstrual cycle day 3 (Protocol A, n = 28) or continued during the period of ovarian stimulation until the day of hCG injection (Protocol B, n = 58). IVF parameters and pregnancy outcome of luteal E2 treatments group were compared with a standard GnRH antagonist protocol (n = 69) which the patients received no hormonal pretreatment. Compared to standard GnRH antagonist protocol, cancellation rate was lower with luteal E2 group (15.1% vs 37.7%, p < 0.01). Moreover, patients treated with luteal estrogen resulted in an increased number of oocytes retrieved (4.5 ± 2.9 vs 3.2 ± 1.9; p < 0.01). A trend toward increase in number of normally fertilized embryos (2.9 ± 2.1vs 2.3 ± 1.9; p = 0.043), and increased prevalence of good quality embryos (51.2% vs 25%; p = 0.047) were noted. Comparing protocol A and B, there were no significant difference between embryologic data, however there were slight increase in ongoing pregnancy rate in protocol B compared to A (27.1% vs 20%, p = 0.357), although statistical significance was not achieved. Estrogen priming through luteal phase and stimulation phase improved ovarian responsiveness and this may lead to an increase in pregnancy rate in poor responders with failed cycle.

Estrogens and men with schizophrenia: Is there a case for adjunctive therapy?

Adjunctive use of estrogen therapy has been shown to be effective in enhancing the treatment of schizophrenia in women. In men, consideration of estrogen therapy has been impacted by concerns of feminising side effects, however, clinical trials of the use of estrogen in treating prostate cancer, bone density loss and even aggression and psychosis in dementia or traumatic brain injury, show this to be a safe and effective therapy. The current 14-day randomised placebo-controlled trial in 53 men with schizophrenia was conducted to evaluate the efficacy of 2 mg oral estradiol valerate as an adjunct to atypical antipsychotic treatment. Results demonstrated for estradiol participants a more rapid reduction in general psychopathology that occurred in the context of greater increases in serum estrogen levels and reductions in FSH and testosterone levels. Approximately 28% of estradiol participants did not achieve an increase (at least a 50% from baseline) in serum estrogen suggesting that further research is needed to refine the type, dose and administration route for estrogen therapy in men. Findings do, however, suggest further exploration of a therapeutic role for adjunctive estradiol treatment in men with schizophrenia is warranted.

The best luteal phase support protocol for patients who had E2 levels

OBJECTIVE: To identify the best protocol for luteal phase support, only progesterone (P), P with hCG or P with hCG plus 6 mg oral estradiol (E2) valerate was treated into patients who had E2 levels <1500 pg/mL on the hCG day in a long GnRH agonist cycles.DESIGN: A prospective study.MATERIALS AND METHODS: 124 patients who underwent IVF/ICSI-ET in a long GnRH agonist cycles had E2 levels <1500 pg/mL on the hCG day or lower E2 levels compared to no. of retrieved oocytes were supported luteal phase by three protocols. Each protocol divides Group I (P only, n=42) with IM P 50 mg/day from OPU day (day 0), Group II (P+hCG, n=41) plus hCG 2000 IU SC on day 0, 2, 4 and Group III (P+hCG+E2, n=39) plus 6mg/day oral E2.Table 1IVF/ICSI cycle characteristics of the investigated groups and comparison of clinical outcome in the three groups.VariableGroup I(IM P)Group II(IM P+hCG)Group III(IM P+hCG+E2)No. of cycles424139Age33.8 ± 4.333.4 ± 3.433.1 ± 3.9E2 level on day hCG(pg/mL)1182 ± 4501084 ± 4531103 ± 489No. of retrieved oocytes8.1 ± 5.77.6 ± 4.78.1 ± 3.9No. of transferred embryos2.8 ± 0.52.9 ± 0.42.9 ± 0.5Endometrium thickness(mm)10.6 ± 2.110.9 ± 2.310.7 ± 1.7IR(%)∗15.7a27.4b28.8bClinical PR(%)∗12(28.6)a20(48.9)b19(48.7)bMiscarrige(%)1(7.7)2(8.7)0(0)Mild OHSS(%)2(4.8)0(0)1(2.4)Means ± SD and % ∗P<0.05. Open table in a new tab CONCLUSION: Patients who had E2 levels <1500pg/mL on the hCG day and lower E2 levels compared to retrieved oocytes in a long GnRH agonist protocol are required additional luteal phase support such as hCG and E2. hCG supplementation is sufficient for luteal phase support without OHSS. OBJECTIVE: To identify the best protocol for luteal phase support, only progesterone (P), P with hCG or P with hCG plus 6 mg oral estradiol (E2) valerate was treated into patients who had E2 levels <1500 pg/mL on the hCG day in a long GnRH agonist cycles. DESIGN: A prospective study. MATERIALS AND METHODS: 124 patients who underwent IVF/ICSI-ET in a long GnRH agonist cycles had E2 levels <1500 pg/mL on the hCG day or lower E2 levels compared to no. of retrieved oocytes were supported luteal phase by three protocols. Each protocol divides Group I (P only, n=42) with IM P 50 mg/day from OPU day (day 0), Group II (P+hCG, n=41) plus hCG 2000 IU SC on day 0, 2, 4 and Group III (P+hCG+E2, n=39) plus 6mg/day oral E2. Means ± SD and % ∗P<0.05. CONCLUSION: Patients who had E2 levels <1500pg/mL on the hCG day and lower E2 levels compared to retrieved oocytes in a long GnRH agonist protocol are required additional luteal phase support such as hCG and E2. hCG supplementation is sufficient for luteal phase support without OHSS.

Hot flushes and biochemical markers for cardiovascular disease: a randomized trial on hormone therapy

Introduction Menopausal hot flushes may affect the responses of various vascular risk factors to hormone therapy (HT). We compared the responses of biochemical markers for cardiovascular diseases to HT in recently postmenopausal women with tolerable or intolerable hot flushes.Methods Healthy, non-smoking freshly postmenopausal women (n = 150) with no previous HT use were studied. Seventy-two women reported intolerable hot flushes (≥7 moderate/severe episodes/day) and 78 women tolerable hot flushes (≤3 mild episodes/day). The participants were treated in randomized order with either transdermal estradiol gel (1 mg), oral estradiol valerate (2 mg) with or without medroxyprogesterone acetate (5 mg), or placebo for 6 months. Treatment-induced changes in lipids, lipoproteins, apolipoproteins, sex hormone binding globulin (SHBG) and high-sensitivity C-reactive protein were compared. The trial is registered in the US National Institutes of Health Clinical Research Registry (no. NCT00668603).Results Pretreatment hot flush status was not related to the responses of these markers to different forms of HT. However, when all active regimens were evaluated together as a post-hoc analysis, 7/10 markers showed a tendency toward greater beneficial changes in women with intolerable hot flushes. Furthermore, in women with intolerable hot flushes and with HT use, the increases in SHBG (Spearman's rho = − 0.570, p < 0.001) were related to the reductions in hot flushes during the use of HT.Conclusions Hot flushes appear to be no significant determinant for the responses of vascular markers to HT use.

Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients

To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle. Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support. There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group. Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS.

Efficacy of luteal supplementation of vaginal sildenafil and oral estrogen on pregnancy rate following IVF-ET in women with a history of thin endometria: A pilot study

Objective: The several strategies for unexplained thin endometrium are under debate. We evaluated the effect of concomitant administration of vaginal sildenafil and oral estrogen in women with a thin endometrium undergoing in vitro fertilization (IVF). Methods: Forty-eight women showing thin endometrium less than 8 mm at the time of embryo transfer were randomly assigned to the study (n=21) and control group (n=27) in their subsequent IVF cycles. Routine luteal support was made by vaginal micronized progesterone 600 mg/day. In the study group, oral estradiol valerate 4 mg/day + vaginal sildenafil 25 mg/day was administered from the day of embryo transfer. Results: The clinical pregnancy rate was two-fold higher in the study group, although it was not statistically significant (47.6% vs. 25.9%, P=0.209). Conclusion: Our study supports that luteal administration of vaginal sildenafil and oral estrogen has modest beneficial impact on the uterine receptivity.

Endometrial priming in oocyte donation: is transdermal route as efficient as the oral one?

OBJECTIVE: Endometrial priming in oocyte donation is mainly performed using oral estrogens. Nearly no data are available about the outcome of egg recipient cycles after the use of transdermal patches. Yet this administration route can have some advantages as it avoids first pass metabolism. To increase evidence about this subject, we analysed our data on a large number of oocyte donation cycles, comparing transdermal to oral administration. DESIGN: All first attempt egg donation cycles performed between 01/07/2005 till 31/08/08 were retrospectively analysed. MATERIALS AND METHODS: Only women aged less than 45 years were included. Oral estradiol valerate was used in a constant 6 mg dose regimen and, if the transdermal route was used, a constant dosage of 150 μg changing patches every 3 days was applied. In both protocols, from the day of the oocyte retrieval 800 mg of micronized vaginal progesterone was added. The embryo replacement was almost exclusively performed at the cleavage stage. RESULTS: A total of 3364 cycles were analysed. In 3059 (91%) the oral route was used and in 305 (9%) the transdermic. The mean recipient age was 38.8 (95%CI 38.6-39.0) versus 39.7 years (39.0-40.3) in the oral and the transdermal group, respectively. The mean number of days of treatment was 26.7 (95% CI 26.2-27.3) versus 26.6 days (95% CI 24.8-28.4), in oral and transdermal respectively. In both groups a mean of 1.9 embryos was replaced. The ongoing pregnancy rate per embryo transfer was 37 (95% CI 35-39) versus 38.8 % (95% CI 35 -45) in the oral and transdermal groups respectively, which is not significantly different OR 1.13 (0.89-1.4). Moreover, no differences were observed in first trimester miscarriages, 17% versus 13%, respectively. CONCLUSIONS: In the present study no difference was found in ongoing pregnancy rate between transdermal and oral groups. However, the transdermic method of administration could be of particular interest in some subgroups of egg recipients. Therefore, further prospective randomized studies should be performed.

IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study

To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol. A prospective, randomized and controlled study. ART center of a state public hospital Two hundred twenty infertile women underwent IVF/ICSI treatments. Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E(2) pre-treatment group n=109) or received standard long GnRH agonist protocol as control group (n=111). Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles. E(2) pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E(2) pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E(2) pre-treatment group had elevated LH at all time (>or= 10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E(2) pre-treatment and control groups. Luteal E(2) pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E(2) pre-treatment during COH has no negative effect on the IVF/ICSI outcomes.

Oestrogen — a new treatment approach for schizophrenia?

The oestrogen protection hypothesis proposes that oestrogen has a protective effect against onset of schizophrenia. In support of this: Epidemiological studies have shown that young women are less likely to develop schizophrenia than men of the same age, and women are more likely to develop late-onset schizophrenia after menopause. Clinical studies have shown higher psychotic symptoms in perimenopausal women, and women at the low oestrogen phase of the menstrual cycle. Animal studies provide further evidence in support of the oestrogen protection hypothesis. Three randomised double-blind placebo-controlled trials and an open-label study showed that adding oestradiol to women's usual antipsychotic medications was associated with significant abatement of schizophrenia symptoms. A small study of men with schizophrenia who received oral oestradiol valerate also showed a significant abatement in psychotic symptoms. Although oestrogen appears to be a useful treatment for schizophrenia, further research is required to determine the correct dose and duration of use of oestradiol. New types of oestrogen compounds may provide a safer, non-feminising approach for the treatment of schizophrenia.

Poor outcome in oocyte donation after elective transfer of a single cleavage-stage embryo in Turner syndrome patients

In this retrospective, matched study we evaluated the outcome of 31 oocyte donation (OD) cycles performed in 29 Turner syndrome (TS) patients involving the elective transfer of a single, fresh cleavage-stage (day 2 to 3) embryo. Due to the fact that ongoing pregnancy rate was statistically significantly lower (3.2% versus 22.5%) in TS patients when compared with matched, non-TS recipients, other strategies (such as single blastocyst transfer) should be evaluated that could enable better outcomes and at the same time avoid potential complications related to multiple pregnancies in this particularly high obstetric-risk group.

Effects of testosterone and estrogen treatment on the distribution of sex hormone receptors in the endometrium of postmenopausal women

Our aim was to investigate the effects of the addition of testosterone to estrogen compared with those of estrogen alone on the expression and distribution of sex hormone receptors in glands and stroma of the endometrium of postmenopausal women. An open, randomized clinical study with parallel group comparison was performed in the Women's Health Research Unit at a university hospital. Thirty-one postmenopausal women were given oral estradiol valerate (2 mg daily) or estradiol valerate in combination with testosterone undecanoate (40 mg every 2 days) for 3 months. Before and at the end of treatment, endometrial biopsy samples were obtained, and expressions of estrogen receptor (ER)-alpha, ER-beta, progesterone receptor isoforms A and B, and androgen receptor (AR) were evaluated by immunohistochemical analysis. At baseline, expressions of ER-alpha and progesterone receptors were stronger in glands than in stroma, whereas the immunostaining of AR was stronger in stroma than in glands. After treatment, expressions of ER-alpha and progesterone receptors were up-regulated in both glands and stroma by both treatments, but to a lesser extent in glands by combined treatment. The expression of ER-beta in glands was significantly higher with combined treatment than with estrogen alone. Moreover, AR immunostaining was significantly higher after combined treatment than after treatment with estrogen alone. Expressions of AR and ER-beta were stronger in glands of the endometrium of postmenopausal women after treatment with testosterone added to estrogen than after estrogen alone. In contrast, expressions of ER-alpha and progesterone receptors were up-regulated in the endometrium with estrogen-alone treatment, whereas these expressions were less increased in glands after combined treatment. These data indicate that testosterone is involved in the regulation of sex hormone receptor expression in the postmenopausal endometrium and may therefore influence endometrial proliferation and differentiation.

Therapeutic dosages of oral or transdermal estradiol did not modify sCD40L levels in postmenopausal women

The CD40/CD40L system is considered a crucial modulator of the inflammatory process underlying the progression and complication of atheroma plaques. The soluble fraction of CD40L (sCD40L) is a reliable indicator of the CD40/CD40L system. Our purpose was to investigate whether a therapeutic dose of estradiol, by either the oral or the transdermal route, was associated with changes in circulating levels of sCD40L. Forty-seven women completed a 4-week course of treatment with either oral estradiol valerate (2 mg/day, 20 women) or transdermal estradiol (50 μg/day, 27 women). Serum levels of sCD40L were measured by conventional enzyme-linked immunosorbent assay. Oral, but not transdermal estradiol, modified the lipid profile. Levels of sCD40L, however, remained unchanged compared with baseline. This neutral effect of oral or transdermal estradiol on sCD40L levels further advances our knowledge on the effects of estrogens on mechanisms involved in the progression and complication of atherosclerosis.

Pregnancy and delivery after freezing and thawing of blastocysts derived from biopsied embryos

Pregnancy and delivery after freezing and thawing of blastocysts derived from biopsied embryos

Does luteal estradiol supplementation have a role in long agonist cycles? does luteal estradiol supplementation have a role in long agonist cycles?

To evaluate the effect of three different modes of luteal support: only progesterone (P), P with 6 mg oral estradiol (E2) valerate and P with 6 mg vaginal E2 valerate on luteal serum E2 levels and patterns and pregnancy rates in women undergoing intracytoplasmic sperm {ICSI} cycles, using the long agonist protocol. Prospective randomized study. 270 infertile patients who were candidate for ICSI cycles, for first time, due to male factor infertility were prospectively included in the study. All participants should have more than 5 mature oocytes at retrieval and at least one good quality embryo available for transfer. In all patients, the long luteal down-regulation protocol was used. From the day of embryo transfer, patients were prospectively randomized to receive either, only P (group A, n = 90), P with 6 mg oral E2 valerate (group B, n = 90) or P with 6 mg vaginal E2 valerate {placed in upper third of vagina}(group C, n = 90) for luteal support. - Luteal E2 and P profiles on days 0 (day of hCG), 7, 10 as well as day 13. Luteal E2 and P levels of the 3 groups were considered together on days 0, 7 and 10. Whereas, on day 13 non-pregnant cases were compared separately in order to rule out the influence of early levels of hCG. Clinical pregnancy rate was documented. Day 0 E2 levels were similar in the 3 groups. Group A had significantly lower E2 levels on days 7, 10 and 13 and a higher magnitude of E2 decline on days 7 and 10 in comparison with those in groups B & C. Similar levels of luteal E2 were documented in groups B and C. Luteal serum P levels were similar in the three groups. The highest pregnancy rate was achieved in group C (45.56%), however, only the difference between group C and A was found to be statistically significant (P=0.031). In addition, a significantly higher early spontaneous abortion rate (ESA) was observed when comparing group A (22.2%) with either group B (3.03%, P=0.002) or group C (2.44%, P=0.035), while, no significant difference was found when comparing group B with group C . Statistical analysis As the data are normally distributed, continuous variables are expressed as mean ±SD. Statistical comparisons were carried out by ANOVA, Chi-square test, Fisher's Exact test or Student's t-test, as indicated. P<0.05 was taken as statistically significant. For patients who are treated with the long agonist protocol, the addition of 6 mg vaginal E2 valerate to P supplementation regimen appears to enhance the probability of pregnancy.

Drospirenone increases central and peripheral β-endorphin in ovariectomized female rats

Drospirenone is the unique progestin derived from 17-spironolactone used for contraception and hormone therapy. Few data are available concerning the effects of drospirenone on the central nervous system and neuroendocrine milieu. The opioid beta-endorphin and the neurosteroid allopregnanolone are considered markers of neuroendocrine functions, and their synthesis and activity are regulated by gonadal steroids. The aim of the present study was to evaluate the effect of a 2-week oral treatment with drospirenone, estradiol valerate, and combined therapy of drospirenone + estradiol valerate on central and peripheral beta-endorphin and allopregnanolone levels in ovariectomized female rats. Seven groups of Wistar ovariectomized rats received oral drospirenone (0.1, 0.5, and 1.0 mg/kg per day), estradiol valerate (0.05 mg/kg per day), or drospirenone (0.1, 0.5, and 1.0 mg/kg per day) + estradiol valerate (0.05 mg/kg per day). One group of fertile and one group of ovariectomized rats were used as controls. beta-endorphin levels were measured in frontal and parietal lobes, hippocampus, hypothalamus, anterior and neurointermediate pituitary, and plasma, and allopregnanolone content was assessed in frontal and parietal lobes, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. Ovariectomy induced a significant decrease in beta-endorphin and allopregnanolone content in all brain areas analyzed and in circulating levels, whereas it increased allopregnanolone content in the adrenal gland. Estradiol valerate replacement increased beta-endorphin and allopregnanolone levels in all brain areas analyzed and in plasma/serum. Drospirenone treatment significantly increased beta-endorphin levels in all brain areas analyzed (with the only exception being the parietal lobe), whereas it produced no effect on allopregnanolone levels. The addition of drospirenone to estradiol valerate did not modify the effects of estradiol valerate on beta-endorphin or allopregnanolone levels. Drospirenone showed an additive and synergistic effect with estradiol in the neurointermediate lobe on beta-endorphin synthesis. Drospirenone significantly increases central and circulating beta-endorphin levels and does not seem to interfere with allopregnanolone production.