Low Doses Of GnRH Research Articles

ANTAGONIST OR PROTAGONIST: ASSESSING STIMULATION PROTOCOLS THROUGH THE LENS OF ARTIFICIAL INTELLIGENCE

To determine if there are differences in oocyte/embryo quality and clinical pregnancy outcomes among patients who undergo either GnRH antagonist or low-dose luteal GnRH agonist (Lupron) stimulation (LDLL) protocols by using deep machine learning algorithms.

The effect of flexible low-dose GnRH antagonist on pregnancy outcome in the fresh embryo transfer cycle of IVF-ET: a randomized controlled trial

ObjectiveTo explore the practicality and effectiveness of a flexible low-dose protocol in the fresh embryo transfer cycle: reducing the total amount of antagonist by increasing the interval between administrations of Cetrotide.MethodsA total of 211 patients with normal ovarian reserve who accepted GnRH-ant protocol for IVF-ET were selected, and they were randomized to the flexible low-dose antagonist group (test group, n = 101) or the conventional dose antagonist group (control group, n = 110). The initial dose of Cetrotide in the test group was 0.25 mg every other day, and then the dose was adjusted to 0.25 mg every day based on the subsequent luteinizing hormone (LH) levels. The dosage of Cetrotide in the control group was 0.25 mg per day. The primary outcome was the clinical pregnancy rate. Secondary outcomes included the incidence of premature LH rise, total dosage of Cetrotide, number of oocytes retrieved, number of fertilized oocytes, number of high-quality embryos, biochemical pregnancy rate and ongoing pregnancy rate.ResultsThere was no significant difference in the general condition of the two groups. There was no significant difference in the clinical pregnancy rate (51.49% vs. 48.18%, p = 0.632) or the incidence of premature LH rise (18.81% vs. 15.45%, p = 0.584) between the two groups. However, the amount of Cetrotide used in the test group was significantly lower than that in the conventional dose antagonist group (1.13 ± 0.41 vs. 1.61 ± 0.59 mg, p < 0.001).ConclusionThe flexible low-dose antagonist protocol and the conventional dose antagonist protocol were equally effective in people with a normal ovarian reserve in the fresh embryo transfer cycle of IVF-ET.

Different Timing of Adjuvant Low Dose hCG and GnRH Agonist Trigger Protocol, in OHSS High-Risk Patient with Peak E2 Level &lt;4000 pg/mL

OBJECTIVE: The aim of the study is to compare the live birth rates between 1,500 I.U. of Human chorionic gonadotropin at the time of Gonadotropin-releasing hormone agonist trigger day or 35-36 h later on the oocyte pick-up day, without affecting the risk of significant ovarian hyperstimulation syndrome development in high-risk patients with peak E2 level &lt;4,000 pg/mL STUDY DESIGN: This single-center prospective cohort study encompassed the period from March 2016 to March 2018 year. A total of 216 patients entered for final analysis, underwent a flexible antagonist protocol, intracytoplasmic sperm injection, and embryo transfer on the 3rd or 5th day in autologous cycles. Patients were randomized in one of two groups: Group A- Dual trigger group - 1,500 IU of Human chorionic gonadotropin at the time of Gonadotropin-releasing hormone agonist trigger day and Group B- 1,500 IU of Human chorionic gonadotropin 35-36 h later, on the oocyte pick-up day. To compare the two groups, we used nonparametric and parametric statistical tests. Significant differences were considered all values of p&lt;0.05. RESULTS: There is no significant difference between the two (A vs B) groups according to the average number of retrieved oocytes (13.08 vs 14.41 p=0.08), M II oocytes (10.5 vs 10.95 p=0.46), GV (1.24 vs 1.52 p=0.09, the fertility rate (68.46% vs 64.04% p=0.07). The dual trigger group (A) had a significantly higher live birth rate (62.29% vs 42.37% p&lt;0.05) compared with the Gonadotropin-releasing hormone-a trigger group (B). There were no cases of moderate or severe ovarian hyperstimulation syndrome in both groups. CONCLUSION: Our study shows that in hyper responders where the E2 peak is &lt;4,000 pg/mL, the two approaches to the final oocyte maturation trigger have a correct outcome of the results, both in terms of the results from the in vitro fertilization and the low risk of ovarian hyperstimulation syndrome appearance.

Flexible Low-Dose GnRH Antagonist Protocol Is Effective in Patients With Sufficient Ovarian Reserve in IVF.

Gonadotropin-releasing hormone antagonist (GnRH-ant) has been shown to negatively influence endometrial receptivity. Reducing the GnRH-ant dose during controlled ovarian stimulation (COS) when using a GnRH-ant protocol may be beneficial to embryo implantation. However, whether or not the minimum daily GnRH-ant dose should be individualized remains uncertain. In this retrospective study, we aimed to elucidate the feasibility and effectiveness of moderately reducing the daily GnRH-ant dose to 0.125 mg, and then adjusting the dose to 0.25 mg based on subsequent luteinizing hormone (LH) levels. Of the 434 patients analyzed in this study, 209 received our new flexible low-dose GnRH-ant protocol (Group 1) and 225 received a conventional GnRH-ant protocol with a fixed daily dose of 0.25 mg (Group 2). Furthermore, 105 and 114 cycles from groups 1 and 2 received fresh embryo transfer. In Group 1, 30 patients whose dose of 0.125 mg GnRH-ant was adjusted according to their LH levels and 179 patients who received consistently low doses were further divided into subgroups 1 and 2, respectively. Neither the number of retrieved oocytes and available embryos nor the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate significantly differed between the two groups. However, GnRH-ant dose and stimulation duration were much lower and shorter in Group 1 than in Group 2 (p < 0.05). Subgroup 1 exhibited higher basal follicle-stimulating hormone (FSH) and lower antral follicle count (AFC) than subgroup 2 significantly. The number of retrieved oocytes and available embryos were lower in subgroup 1 than in subgroup 2 (6.83 ± 3.28 vs. 11.83 ± 4.82, 2.93 ± 1.86 vs. 4.99 ± 3.46, respectively, p < 0.05), while more canceled cycles for pre-ovulation occurred in subgroup 1 than in subgroup 2 (3/30 vs. 1/179, p < 0.05). The results showed that the flexible low-dose GnRH-ant protocol was as effective as the conventional fixed-dose GnRH-ant protocol with 0.25 mg per day for most patients with normal ovarian reserve. This retrospective analysis and the small sample size are the main limitations of this study, and a large sample RCT will be carried out in the future.

Increased Uterine NK cell numbers and perforin expression during the implantation phase in IVF Cycles with GnRH Antagonist Protocol

GnRH antagonist negatively affects endometrial receptivity in in vitro fertilization (IVF) cycles, however, its underlying mechanism remains unclear. To explore its target molecules, we studied endometria in the window phase of fixed GnRH antagonist, low-dose flexible GnRH antagonist, GnRH agonist long protocol, and untreated control groups. There were 384 differentially expressed genes (DEGs) in the fixed antagonist group with greater than twofold expression change compared with the control group and 197 DEGs between the fixed antagonist and agonist groups, the majority of which were associated with the natural killer (NK) cell-mediated cytotoxicity pathway. We then analysed the PRF1 and FASLG protein levels. The perforin level were significantly higher in both the antagonist groups than in other two groups, and was higher in the fixed antagonist group. Similarly, the uNK cell numbers were higher in the antagonist groups, and the highest uNK cell number occurred in the fixed group (p < 0.05). No significant differences existed in the Fas ligand levels and apoptosis rates among the three treatment groups, but were higher in the treatment groups than the control group. Together, these data indicate that GnRH antagonist may increase the uNK cell numbers and perforin expression, and this effect may be dose-dependent.

Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support-Results of a Prospective, Randomized, Comparative Study.

Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B). Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group. Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols.

Effect of gonadotropin-releasing hormone agonist on ES-2 ovarian cancer cells

ObjectiveGonadotropin-releasing hormone (GnRH) receptor is found in the ovarian tissue, including epithelial ovarian cancer (EOC), suggesting that GnRH agonists may have direct action on EOC. Materials and methodsOvarian clear cell cancer (ES-2) cells were treated with low-dose GnRH agonist with/without low-dose paclitaxel (1 μM D-Lys6 with/without 0.5 μM or 1.0 μM paclitaxel). Growth and behavior of ES-2 cells were evaluated. ResultsUse of either D-Lys6 or paclitaxel or a combination of the two did not affect the morphology and growth pattern of ES-2 cells. However, ability of migration and invasion of ES-2 cells was significantly decreased in either use of D-Lys6 or paclitaxel and more apparent with the combination. Type I GnRH receptor expression of ES-2 was not altered significantly by the combination. ConclusionGnRH agonist might modify the ES-2 ovarian cancer cells, and its role might be independent, additional or synergistic, suggesting the potential role of the use of GnRH agonist in the management of clear cell type of the ovarian cancer. However, the results of this study were derived using ES-2 ovarian cancer cells, and might not be valid in other cell types of ovarian cancers.

Pregnancy and neonatal outcomes following luteal GnRH antagonist administration in patients with severe early OHSS

Do high-risk patients who develop severe early ovarian hyperstimulation syndrome (OHSS) and receive low-dose GnRH antagonist in the luteal phase have lower live birth rates compared with high-risk patients who do not develop severe early OHSS and do not receive GnRH antagonist in the luteal phase? Low-dose luteal GnRH antagonist administration in women with severe early OHSS is associated with similar live birth rates to that of high-risk patients who do not develop severe early OHSS and do not receive GnRH antagonist in the luteal phase. It has been reported that luteal GnRH antagonist administration in patients with established severe early OHSS appears to prevent patient hospitalization and results in quick regression of the syndrome on an outpatient basis. However, the effect of such treatment on pregnancy outcome has been investigated in only a small number of animal studies. This is a prospective cohort study of 192 IVF patients who were at high risk for OHSS and who did not wish to cancel embryo transfer and have all embryos cryopreserved. The study was conducted between January 2009 and December 2011 at Eugonia Assisted Reproduction Unit. Patients were <40 years of age, with polycystic ovaries, at high risk for OHSS (defined by the presence of at least 20 follicles ≥11 mm on the day of triggering of final oocyte maturation) and not willing to cancel embryo transfer and cryopreserve all embryos, if severe early OHSS was diagnosed by Day 5 of embryo culture. Patients who were diagnosed with severe early OHSS on Day 5 post-oocyte retrieval were administered 0.25 mg of ganirelix for 3 days, from Day 5 until and including Day 7 (OHSS + antag group, n = 22). High-risk patients who did not develop the severe early OHSS did not receive GnRH antagonist in the luteal phase (control group, n = 172). All patients underwent embryo transfer on Day 5. Live birth rates (40.9 versus 43.6%), ongoing pregnancy rates (45.5 versus 48.8%), clinical pregnancy rates (50 versus 65.1%), positive hCG (72.7 versus 75%), duration of gestation (36.86 ± 0.90 weeks versus 36.88 ± 2.38 weeks) and neonatal weight (2392.73 ± 427.04 versus 2646.56 ± 655.74 g) were all similar in the OHSS + antag and control groups, respectively. The incidence of major congenital malformations was 2.9% (3/103) in children born in the control group compared with no cases (0/14) in children born following luteal GnRH antagonist administration. No stillbirths or intrauterine deaths, and no cases of pregnancy-induced late OHSS were recorded in either group. None of the 22 patients with severe early OHSS required hospitalization following luteal antagonist administration. Ovarian volume, ascites, hematocrit, white blood cell count, serum estradiol and progesterone decreased significantly (P < 0.001) by the end of the monitoring period (Day 11 post-oocyte retrieval), indicating rapid resolution of the severe OHSS. This is a prospective cohort investigation with a very limited number of patients receiving the intervention and a larger number of control patients. Our findings suggest that low-dose luteal GnRH antagonist administration during the peri-implantation period may be safe, although larger studies with follow-up of the children born are required. Our study suggests for the first time that low-dose luteal GnRH antagonist administration in women with severe early OHSS is associated with a favourable IVF outcome, comparable to control high-risk patients without severe OHSS and not receiving the intervention. Regarding the wider implications on the concept of an OHSS-free clinic, administration of GnRH antagonist in the luteal phase may present a tertiary management level in patients with established severe OHSS, along with the use of GnRH antagonist protocols for primary prevention and the replacement of hCG with GnRH agonist for triggering final oocyte maturation for secondary prevention. However, at present, fresh embryo transfer combined with antagonist administration should only be used with caution by experienced practitioners, after carefully deciding which patients can have a fresh transfer or embryo cryopreservation, until the current data are confirmed by larger trials.

Controlled Ovarian Hyperstimulation through Gonadotrophin releasing Hormone Agonist for Patients at Risk of Hyperstimulation Syndrome

Background:Patients at high risk of OHSS can experience difficulty in completing an IVF cycle with the administration of gonadotrophins. Here, we test a unique low-dose GnRH agonist protocol. Methods: 0.1mg triptorlin acetate (decapeptyl) was administered to 18 patients at high risk of OHSS from day 5 of the menstrual cycle. Oocyte retrieval was performed 36 hours after the administration of 10000 IU human chorionic gonadotrophin, when follicles of 18-20mm were observed. Oocytes were fertilised in vitro and embryos transferred on day 3. Results: Patients produced a mean of 4.1 ± 0.96 oocytes. After ICSI, a mean of 3.0 ± 0.84 embryos were transferred to the uterus. A total of 5 pregnancies were obtained from the 18 cycles. No patients were affected by OHSS. Conclusions: Low-dose injections of GnRH analogues can cause multiple follicular development, mature oocytes and pregnancies in patients at risk of OHSS. This novel COH protocol appears safe and applicable as a valuable alternative to the natural cycle.

Ganirelix for luteolysis in poor responder patients undergoing IVF treatment: a Scandinavian multicenter ‘extended pilot study’

To enhance oocyte yield and pregnancy outcome in poor responder women undergoing IVF treatment, daily low dose GnRH antagonist administration was given during the late luteal phase to induce luteolysis and possibly secure a more synchronous cohort of recruitable follicles. An open extended pilot study in four Scandinavian fertility centers was done including 60 patients. Poor response was defined as when < or = 5 follicles developed in a preceding cycle following a long agonist protocol with the use of > 2000 IU FSH. GnRH antagonist (ganirelix) was given, 0.25 mg s.c. daily, from days 3 to 5 before expected start of menstruation and continued for 4-7 days. On cycle day 2-3 a starting dose of rFSH (300-400 IU/day) was given. At a leading follicle diameter of 14 mm, ganirelix administration was resumed until final oocyte maturation was induced with 10,000 IU hCG. GnRH antagonist only marginally affected the intercycle FSH rise; basal levels of FSH remained similar to those seen after 4 days of antagonist administration. The protocol effectively induced low LH levels and luteolysis, but daily administration of 350 IU rFSH (median) for 11 days only led to the collection of 3 oocytes in 49 oocyte retrievals resulting in 5 pregnancies (4 delivered). Despite GnRH antagonist administration in the late luteal phase and menstrual bleeding, FSH was not sufficiently reduced to secure a more synchronic cohort of recruitable follicles. Novel GnRH antagonists more specifically targeting FSH release may improve the stimulation results in poor responders.

Affordable ART for developing countries: a cost benefit comparison of low dose stimulation versus high dose GnRH antagonist protocol

Low dose stimulation (LS) is emerging as an alternative regime in assisted reproductive technology (ART). This study aimed to compare the cost-effectiveness of LS to the high dose GnRH antagonist (Atg) regime. An observational prospective study conducted at an academic infertility unit from January to June 2007. Outcome measures included the numbers of follicles, oocytes and embryos, morphological quality of oocytes and embryos, clinical pregnancy (PR) and complication rate. Ninety five first attempt ICSI cycles consisting of 54 LS and 41 Atg were analyzed. Subjects in both groups had comparable sociodemographics and reproductive characteristics. LS generated significantly fewer follicles, total oocytes, mature oocytes (all p < 0.0005) and immature oocytes (p = 0.009) than Atg but the number of excellent quality oocytes was similar. Significantly fewer embryos were available in LS although the proportion of usable embryos was higher, 83.2% vs. 67.0% for Atg. Mean embryos per transfer was 2.0 +/- 1.1 vs. 2.6 +/- 1.0 (p = 0.02) for a clinical PR per transfer of 43.2% vs. 50.0% for LS and Atg respectively. LS regime had a shorter gonadotrophin administration period with resultant COH cost one third of the Atg protocol (both, p < 0.0005). The cost per live birth per started cycle worked out to be USD 13,200 and 24,900 for LS and Atg respectively. Furthermore, LS had fewer incidences of OHSS compared to the Atg regime, 3.7% vs. 12.2%. LS cost benefits included lower amounts of gonadotrophin used and fewer injections. It is a viable alternative regime in producing comparable clinical PR at lower cost and less complication in ART.

Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis

Spine density in the hippocampus changes during the estrus cycle and is dependent on the activity of local aromatase, the final enzyme in estrogen synthesis. In view of the abundant gonadotropin-releasing hormone receptor (GnRH-R) messenger RNA expression in the hippocampus and the direct effect of GnRH on estradiol (E2) synthesis in gonadal cells, we asked whether GnRH serves as a regulator of hippocampal E2 synthesis. In hippocampal cultures, E2 synthesis, spine synapse density, and immunoreactivity of spinophilin, a reliable spine marker, are consistently up-regulated in a dose-dependent manner at low doses of GnRH but decrease at higher doses. GnRH is ineffective in the presence of GnRH antagonists or aromatase inhibitors. Conversely, GnRH-R expression increases after inhibition of hippocampal aromatase. As we found estrus cyclicity of spine density in the hippocampus but not in the neocortex and GnRH-R expression to be fivefold higher in the hippocampus compared with the neocortex, our data strongly suggest that estrus cycle–dependent synaptogenesis in the female hippocampus results from cyclic release of GnRH.

Continuous administration of low-dose GnRH in mares: II. Pituitary and ovarian responses to uninterrupted treatment beginning near the autumnal equinox and continuing throughout the anovulatory season

We tested the hypothesis that continuous subcutaneous treatment with low-dose GnRH, administered to mares from late September/early October through March, would prevent the development of seasonal anovulation. Quarter Horse mares ( n = 20) were stratified by age and body condition score and assigned randomly to either a saline control ( n = 9) or a GnRH ( n = 11) treatment group. Gonadotropin-releasing hormone was delivered continuously via osmotic minipumps, with sham pumps placed in control mares. Initial pumps were inserted on Day 3 following ovulation or during the follicular phase if the next anticipated ovulation did not occur by 9 October. Delivery rate of GnRH was 2.5 μg/h (60 μg/day) for the first 60 days, followed by 5.0 μg/h (120 μg/day) thereafter. Pumps were replaced every 30 days. Eighty and 100% of all mares had become anovulatory by 1 November and 1 December, respectively, and remained anovulatory through the end of February. Neither serum concentrations of LH throughout the study nor total releasable pools of LH in March differed between groups. Although control mares that exhibited ovulatory cycles after study onset had greater ( P < 0.05) mean concentrations of LH during the follicular phase and metestrus compared to GnRH-treated mares, neither size of ovulatory follicles nor interovulatory intervals differed between groups. Serum concentrations of FSH were not affected by treatment, but were lowest ( P < 0.05) from November through January. Continuous infusion of low-dose GnRH, beginning soon after autumnal equinox and continuing until just after vernal equinox, failed to prevent the occurrence of or to hasten transition from seasonal anovulation.

Continuous administration of low-dose GnRH in mares: I. Control of persistent anovulation during the ovulatory season

Three experiments were conducted during the operational breeding season to confirm that continuous, subcutaneous infusion of low-dose GnRH would not disrupt established estrous cycles (Experiment 1), and test the hypotheses that a similar treatment would stimulate secretion of LH and induce development of ovulatory follicles in persistently anovulatory mares (Experiments 2 and 3). Treatment with GnRH (5 μg/h) increased ( P < 0.001) serum P4 during the luteal phase (7.7 ± 0.5 versus 6.4 ± 0.5 ng/mL), tended to increase serum LH (2.6 ± 0.27 versus 1.9 ± 0.25 ng/mL), and did not modify interovulatory intervals. In Experiment 2, GnRH treatment (2.5–5 μg/h) of persistently anovulatory mares increased ( P < 0.001) serum LH compared to controls (0.5 ± 0.08 versus 0.1 ± 0.03 ng/mL), with all GnRH-treated and no Control mares ovulating. Mares exhibiting Delayed Recrudescence ( n = 29) or Lactational Anovulation ( n = 18), were assigned randomly in Experiment 3 to receive either (1) GnRH/GnRH ( n = 23); 2.5 μg GnRH/h for 14 d (Period I) and 5 μg/h during the subsequent 28 d (Periods II and III); or (2) Control/GnRH ( n = 24); no treatment during Period I (control period) and GnRH treatments as in 1 during Periods II and III. Percentage of mares ovulating and pregnant during Period I was greater ( P < 0.05) for GnRH-treated than Control mares. Thereafter, cumulative ovulation frequency (85%), pregnancy (72%) and cycles/conception (1.3 ± 0.2) were similar between groups; however, interval to conception was reduced ( P < 0.01) by 10.3 d in GnRH/GnRH compared to Control/GnRH.

P-759: Low dose GnRH-a protocol versus GnRH antagonist protocol in the management of poor responders undergoing IVF

P-759: Low dose GnRH-a protocol versus GnRH antagonist protocol in the management of poor responders undergoing IVF

P-15: Early substitution of low dose GnRH antagonist improves ART outcomes in normal responders who have failed a standard, long GnRH agonist protocol

P-15: Early substitution of low dose GnRH antagonist improves ART outcomes in normal responders who have failed a standard, long GnRH agonist protocol

Low-Dose Lupron-Depot With GnRH Antagonist Rescue: A Novel Pituitary Down-Regulation Protocol During Controlled Ovarian Hyperstimulation (COH) for Assisted Reproductive Technology (ART)

To study the effectiveness of a novel low-dose GnRH agonist depot in suppressing endogenous LH surge, and compare treatment outcome to routine pituitary down-regulation protocols (GnRH-agonist long, & GnRH antagonist protocols).

Basal and gonadotropin-releasing hormone-releasable serum follicle-stimulating hormone charge isoform distribution and in vitro biological-to-immunological ratio in male puberty.

Follicle-stimulating hormone is synthesized and secreted as a mixture of heterogeneous isoforms that differ from each other in carbohydrate structure, biological potency, and plasma half-life. The relative abundance of the FSH isoforms will depend on the endocrine status of the donor at the time of sample collection. In the present study, we attempted to define the impact of the changing endocrine milieu characteristic of male puberty on the charge heterogeneity and plasma half-life of the serum FSH isoforms released under endogenous and exogenous GnRH drives, and examined whether such a varying hormone milieu modifies the capability of the circulating hormone to trigger intracellular signal transduction at the human FSH receptor level. Forty healthy male subjects at Tanner stages (Ts) 1 to 5 were sampled at 10 min intervals for 10 h. Serum from successive samples collected across 2-4 h intervals containing FSH released under basal, low-dose (10 microg), and high-dose (90 microg) exogenous GnRH-stimulated conditions was subjected to preparative chromatofocusing and tested for bioactivity employing a homologous cell in vitro bioassay system. Deconvolution analysis was applied to estimate the apparent endogenous FSH plasma half-life in samples obtained after administration of low-dose exogenous GnRH. Under all conditions studied, serum FSH charge isoforms were distributed along a pH range of 7.0 to less than 3.0. Comparisons across the different Tanner stages revealed a significant and selective increase in the ratio of FSH isoforms with elution pH values <4.50 relative to those with values >/=4.50 at Ts-2. At Ts-3, this ratio returned to that present at Ts-1, to decline thereafter during the ensuing pubertal stages. Serum bioactive FSH concentrations progressively increased (from 3.72 +/- 1.3 to 16.2 +/- 5.3 IU/L) throughout puberty, and in all conditions bioactive FSH concentrations exceeded those detected by a specific radioimmunoassay. The biological to immunological (B:I) FSH ratio at baseline was significantly (p < 0.05) lower at Ts-1 and Ts-2 (1.33 +/- 0.30 and 1.62 +/- 0.34, respectively) than at more advanced stages of pubertal development (2.28 +/- 0.20, 2.96 +/- 0.38, and 2.77 +/- 0.63 at Ts-3-, 4-, and -5, respectively) Similar differences were detected in samples containing FSH molecules released after low- and high-dose GnRH administration. The apparent endogenous FSH half-life of the deconvolved GnRH-induced FSH pulses was similar in the five study groups. These results demonstrate that the transition from infancy to sexual maturity in men is accompanied by qualitative changes in the circulating FSH isoform mixture. Although the changes in FSH glycosylation occurring throughout puberty are not of sufficient magnitude to alter the survival of the gonadotropin in circulation, they allow preferential secretion of bioactive FSH. The enrichment of the circulating mix of FSH isoforms with highly bioactive variants throughout spontaneous puberty may potentially favor the development of spermatogenesis and acquisition of reproductive competence.

A randomized, controlled trial of low dose GnRH antagonist started on day 2 in “poor responders” undergoing stimulation with luteal phase GNRH agonist, estrogen priming and high-dose FSH

A randomized, controlled trial of low dose GnRH antagonist started on day 2 in “poor responders” undergoing stimulation with luteal phase GNRH agonist, estrogen priming and high-dose FSH

Intrauterine inseminations without twins: A new milder ovarian stimulation

Objective: Multiple pregnancies represent a serious risk in ART procedures, especially in ovulation induction with and without intrauterine insemination (IUI). The aim of our study was to obtain monofollicular cycles and single pregnancies with a new milder method of ovarian stimulation, using low dose gonadotrophins and GnRH antagonist in IUI cycles. Design: Multicentric randomized clinical trial. Materials/Methods: Patients with at least two years of unexplained infertility or mild male factor were randomized in two groups: group A was treated with recombinant FSH (r-FSH) 50 IU daily (Puregon, Organon) starting from the third day of cycle; patients in group B received r-FSH 50 IU on alternate days. GnRH antagonist (Orgalutran, Organon) at the dose of 0,25 mg daily was started, in both groups, from mean follicle diameter of 13–14 mm at ultrasound. Daily serum E2 were obtained during GnRH antagonist therapy; in addition, serum LH and progesterone (P) were assessed in hCG day. No supplementation was given and serum E2 and P were dosed at +2, +4, +6, +8, +10 from hCG day. Results: A total of 47 patients were recruited. Thirty-six cycles in 36 patients were fully evaluable. Mean estradiol serum levels in each group showed a plateau on day one after GnRH antagonist administration, then had a normal increase. Twenty-one cycles were monofollicular (44,4% in group A and 72,2% in group B); no more than two leader follicles (≥16 mm in diameter) developed and in almost 80% of cases no follicles of 11–15 mm in diameter were present at hCG. Progesterone profile showed a normal ovulatory pattern in both groups. In the 36 completed cycles, pregnancy rate was 27,7%; with the daily FSH administration, group A patients had an unexpectedly high pregnancy rate (42%) compared to that registered in group B (10%)(p <0,05) (table). TableResults in 38 cyclesGroupP ≥ 8 ng/mlN. follicles ≥16 mmN. follicles ≥11 mmPregnancy12≥312≥3N. (PR)SingletonA18 (95)8 (44)10 (56)0 (0)4 (22)10 (56)4 (22)8 (42)†p < 0.058 (100)B18 (95)13 (72)5 (28)0 (0)9 (50)6 (33)3 (17)2 (10)2 (100)Numbers in brackets are percentages. P: Progesterone in mid-luteal phase. PR: Pregnancy Rate.† p < 0.05 Open table in a new tab Numbers in brackets are percentages. P: Progesterone in mid-luteal phase. PR: Pregnancy Rate. Conclusions: The daily low-dose gonadotrophin and GnRH antagonist regimen induced 58,3% monofollicular cycles and, most important, was constantly associated with singleton pregnancies. Pregnancy rate was significantly different for the two methods of stimulation, being the daily regimen more effective. GnRH antagonist had, nor in follicular neither in luteal phase, detrimental effect on the ovarian stimulation. The remarkably high pregnancy rate associated to monofollicular cycles, is probably related to the proper timing of IUI due to GnRH antagonist administration. Supported by: none.