GnRH Agonist Stimulation Research Articles

In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland.

EGR1 and PITX1 are transcription factors required for gonadotroph cell Lhb promoter activation. To determine changes in Egr1 and Pitx1 mRNA levels in central and peripheral pituitary stimulations, an in vivo model based on i.c.v. pulsatile (1 pulse/0.5 h over 2 h) GnRH agonist (1.5 nM buserelin) or antagonist (2 nM antide) microinjections was used. The microinjections were given to ovariectomised and 17β-oestradiol (E2) (3×20 μg), ERA (ESR1) agonist propyl pyrazole triol (PPT) (3×0.5 mg), ERB (ESR2) agonist diarylpropionitrile (DPN) (3×0.5 mg) s.c. pre-treated rats 30 min after last pulse anterior pituitaries were excised. Relative mRNA expression was determined by quantitative RT-PCR (qRT-PCR). Results revealed a gene-specific response for GnRH and/or oestrogenic stimulations in vivo. Buserelin pulses enhanced Egr1 expression by 66% in ovariectomised rats, whereas the oestradiol-supplemented+i.c.v. NaCl-microinjected group showed a 50% increase in Egr1 mRNA expression. The oestrogenic signal was transmitted via ERA (ESR1) and ERB (ESR2) activation as administration of PPT and DPN resulted in 97 and 62%, respectively, elevation in Egr1 mRNA expression. A synergistic action of GnRH agonist and 17β-oestradiol (E2) stimulation of the Egr1 gene transcription in vivo were found. GnRHR activity did not affect Pitx1 mRNA expression; regardless of NaCl, buserelin or antide i.c.v. pulses, s.c. oestrogenic supplementation (with E2, PPT or DPN) consistently decreased (by -46, -48 and -41% respectively) the Pitx1 mRNA in the anterior pituitary gland. Orchestrated Egr1 and Pitx1 activities depending on specific central and peripheral regulatory inputs could be responsible for physiologically variable Lhb gene promoter activation in vivo.

Random unstimulated pediatric luteinizing hormone levels are not reliable in the assessment of pubertal suppression during histrelin implant therapy

BackgroundGonadotropin-releasing hormone agonist (GnRHa)-stimulated luteinizing hormone (LH) is the standard hormonal assessment for both diagnosis and therapeutic monitoring of children with central precocious puberty (CPP). Use of unstimulated (random) LH levels may be helpful in diagnosis and has gained popularity in monitoring GnRHa therapy despite lack of validation against stimulated values. The objective of this investigation was to assess the suitability of random LH for monitoring pubertal suppression during GnRHa treatment.MethodsData from a multi-year, multicenter, open-label trial of annual histrelin implants for CPP was used for our analysis. Children meeting clinical and hormonal criteria for CPP, either naïve to GnRHa therapy or previously treated with another GnRHa for at least 6 months who were being treated at academic pediatric centers were included in the study. Subjects received a single 50-mg subcutaneous histrelin implant annually until final explant at an age determined at the discretion of each investigator. Monitoring visits for physical examination and GnRHa-stimulation testing were performed at regular intervals. The main outcome measure was pubertal suppression during treatment defined by peak LH < 4 mIU/mL after GnRHa stimulation.ResultsDuring histrelin treatment, 36 children underwent a total of 308 monitoring GnRHa stimulation tests. Unstimulated and peak LH levels were positively correlated (r = 0.798), and both declined from the first to second year of treatment. Mean ± SD peak LH level during therapy was 0.62 ± 0.43 mIU/mL (range, 0.06–2.3), well below the normal prepubertal mean. Mean random LH was 0.35 ± 0.25 mIU/mL (range, 0.04–1.5), 10-fold higher than the normal prepubertal mean. The random LH levels were above the prepubertal upper threshold (<0.3 mIU/mL) in 48.4% of all tests and in 88.9% of subjects at some point during therapy.ConclusionsIn contrast with GnRHa-stimulated LH, unstimulated LH values frequently fail to demonstrate suppression to prepubertal values during GnRHa therapy for CPP, despite otherwise apparent pubertal suppression, and are thus unsuitable for therapeutic monitoring.Trial registrationClinicalTrial.gov NCT00779103.

Phenotypically distinct theca cell responses to gonadotropin administration in women with polycystic ovary syndrome

Women with PCOS have heterogeneous ovarian steroid production following GnRH agonist stimulation as 50% demonstrate exaggerated 17-hydroxyprogesterone (17-OHP) responses while the remainder exhibit responses equivalent to normal women. To determine whether this dichotomous 17-OHP response persists following independent administration of LH or FSH, ovarian responses to hCG and FSH were assessed in women with PCOS and normal women.

Rat Gnrhr promoter directs species-specific gene expression in the pituitary and testes of transgenic mice

The GnRH receptor (GnRHR) is expressed in several non-pituitary tissues, notably in gonads. However, mechanisms underlying the gonad-specific expression of Gnrhr are not well understood. Here, Gnrhr expression was analysed in the developing testes and pituitaries of rats and transgenic mice bearing the human placental alkaline phosphatase reporter gene (ALPP) under the control of the rat Gnrhr promoter. We showed that the 3.3 kb, but not the pituitary-specific 1.1 kb promoter, directs ALPP expression exclusively to testis Leydig cells from embryonic day 12 onwards. Real-time PCR analysis revealed that promoter activity displayed the same biphasic profile as marker genes in Leydig cells, i.e. abrupt declines after birth followed by progressive rises after a latency phase, in coherence with the differentiation and evolution of foetal and adult Leydig cell lineages. Interestingly, the developmental profile of transgene expression showed high similarity with the endogenous Gnrhr profile in the rat testis, while mouse Gnrhr was only poorly expressed in the mouse testis. In the pituitary, both transgene and Gnrhr were co-expressed at measurable levels with similar ontogenetic profiles, which were markedly distinct from those in the testis. Castration that induced pituitary Gnrhr up-regulation in rats did not affect the mouse Gnrhr. However, it duly up-regulated the transgene. In addition, in LβT2 cells, the rat, but not mouse, Gnrhr promoter was sensitive to GnRH agonist stimulation. Collectively, our data highlight inter-species variations in the expression and regulation of Gnrhr in two different organs and reveal that the rat promoter sequence contains relevant genetic information that dictates rat-specific gene expression in the mouse context.

Diminished Ovarian Reserve, Causes, Assessment and Management

ABSTRACTDiminished ovarian reserve predicts diminished ovarian response to stimulation but does not predict cycle fecundity. It has been recently defined by ESHRE, the Bologna's criteria, according to which at least two of the following three features should be present: (1) Age &gt;40 years/any other risk factor for DOR, (2) abnormal ovarian reserve test, i.e. antral follicle count, AMH, (3) poor ovarian response in a previous stimulated cycle, i.e. less than three follicles after standard gonadotropin stimulation. Poor response to maximal stimulation on two previous occasions also defines DOR.The treatment options are limited. Avoiding the GnRH agonist long protocol and stimulation with microdose flare or antagonist protocol yields better results. Adjuvant therapy with LH, DHEAS and growth hormone shows some benefit in improving the oocyte yield. It is advisable to perform ICSI for all obtained oocytes and some advocate assisted hatching. Pregnancy rates are, however, poor and often these patients require ovum donation. Developing tests that will diagnose DOR in a low-risk population will allow women to plan their reproductive careers early.How to cite this articleKaur M, Arora M. Diminished Ovarian Reserve, Causes, Assessment and Management. Int J Infertility Fetal Med 2013;4(2):45-55.

Hyperinsulinemia Amplifies GnRH Agonist Stimulated Ovarian Steroid Secretion in Women with Polycystic Ovary Syndrome

In vitro data show that insulin may enhance basal and LH-stimulated ovarian androgen secretion, particularly in theca cells from women with polycystic ovary syndrome (PCOS). However, in vivo studies gave inconsistent results. The objective of the study was to assess whether hyperinsulinemia affects in vivo ovarian steroid secretion and steroid metabolism. This was a controlled cross-sectional study, conducted in a tertiary care academic center. Nine young PCOS women participated in the study. Participants were submitted, in two separate days, to a GnRH agonist stimulation (buserelin 100 μg, s.c.), during a 17-h hyperinsulinemic (80 mU/m(2) · min) euglycemic clamp and, as a control, during saline infusion. Adrenal steroid secretion was suppressed by dexamethasone. During both protocols, before and after GnRH agonist stimulation, serum insulin, gonadotropins, cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, estradiol, and urinary androgen metabolites were measured. Insulin increased from 25.1 ± 13.3 to 341.5 ± 102.6 mU/liter during the clamp, whereas it did not significantly change during saline infusion. Baseline steroids and gonadotropins were similar in the two protocols. During hyperinsulinemia, GnRH agonist-stimulated serum progesterone and androstenedione were significantly higher than during saline infusion, and 17-hydroxyprogesterone was of borderline significance. Moreover, 24 h after GnRH agonist stimulation, testosterone was higher after hyperinsulinemia. Serum gonadotropins and estradiol response did not differ between the protocols. Urinary androgen metabolites excretion significantly increased after GnRH agonist stimulation, but the increase was similar during insulin and saline infusions. These in vivo data show that sustained hyperinsulinemia potentiates gonadotropin-stimulated ovarian androgen steroidogenesis. Insulin-induced increase in ovarian hormone secretion is not accompanied by an increased steroid metabolism.

Possibilities and Limits of Ovarian Reserve Testing in ART

Markers of ovarian reserve are associated with ovarian aging as they decline with chronologic age, and hence may predict stages of reproductive aging including the menopause transition. Assessment of ovarian reserve include measurement of serum follicle stimulating hormone (FSH), anti-M�llerian hormone (AMH), and inhibin-B. Ultrasound determination of antral follicle count (AFC), ovarian vascularity and ovarian volume also can have a role. The clomiphene citrate challenge test (CCCT), exogenous FSH ovarian reserve test (EFORT), and GnRH-agonist stimulation test (GAST) are dynamic methods that have been used in the past to assess ovarian reserve. In infertile women, ovarian reserve markers can be used to predict low and high oocyte yield and treatment failure in women undergoing in vitro fertilization. However the markers may have limitations when an in depth analysis of their accuracy, cost, convenience, and utility is performed. As ovarian reserve markers may permit the identification of both the extremes of ovarian stimulation, a possible role for their measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in the ovarian reserve testing before initiation of an IVF cycle and whether the ovarian reserve markers-determined strategy of ovarian stimulation for assisted conception may be associated to improved live birth rate.

Evaluation of GnRH analogue testing in diagnosis and management of children with pubertal disorders

Context:Gonadotrophin releasing hormone (GnRH) stimulation test is pivotal in the assessment of children with pubertal disorders. However, lack of availability and high cost often result in the test falling into disfavor. We routinely use the GnRH analogue stimulation test as an alternative at our center.Aim:To present the data on children with endocrine disorders who underwent GnRH agonist stimulation test in pediatric endocrine clinic of a tertiary care referral hospital.Setting and Design:Pediatric endocrine clinic of a tertiary care referral hospital. Retrospective analysis of case records.Materials and Methods:The details pertaining to clinical and radiological parameters and hormonal tests were retrieved from case records of 15 children who underwent GnRH agonist stimulation test from May 2010 to April 2011.Results:Indications for testing with GnRH analogue were evaluation of delayed puberty, diagnosis of precocious puberty, assessment of hormonal suppression in treatment of precocious puberty and micropenis in two, nine, three and one cases, respectively. The results of the test and clinical and radiological parameters were in concordance. The test was also crucial in diagnosing the onset of central precocious puberty in two children with congenital adrenal hyperplasia.Conclusion:GnRH agonist test is a convenient, safe test that can be performed on an out-patient basis and can help the clinicians in the correct diagnosis and appropriate treatment of various puberty-related disorders.

Use of letrozole challenge test to adjust gonadotropin dose in non–down-regulated cycles

The use of a letrozole challenge test to predict ovarian response is described. The authors show that a ratio of cycle day 7 to cycle day 3 post-letrozole FSH level >1.5 is associated with poor ovarian response.

Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients at high risk of ovarian hyperstimulation syndrome: a prospective randomized controlled trial

OBJECTIVE: To compare the flexible GnRH antagonist and the GnRH agonist long protocol in patients at high risk of OHSS undergoing IVF.DESIGN: Single-centre open label randomized prospective study.MATERIALS AND METHODS: The study included 144 women who had moderate or severe OHSS or had been at risk of OHSS during their first IVF/ICSI cycle with a mid-luteal long GnRH agonist plus gonadotrophin stimulation protocol. Patients were randomized to receive either cetrorelix 0.25 mg/day starting on day 3 of the menstrual cycle (antagonist group) or triptorelin 0.1 mg/day starting on day 21 of the menstrual cycle (agonist group). Ovarian stimulation was achieved with rFSH initiated on day 3 of the cycle at the maximal dose of 150 IU; the dose was adjusted depending on ovarian response. Embryo transfer was performed 2 or 3 days after oocyte retrieval. Luteal phase support was started on the day of oocyte retrieval using micronised progesterone vaginal gel.RESULTS: The two groups were similar in mean age, duration of infertility, body mass index, baseline FSH, total amount of rFSH administered and proportion of patients undergoing intracytoplasmic sperm injection. When oocyte maturation was triggered, the levels of E2 were lower in the antagonist group than in the agonist group (p<0.001). The number of cancelled cycles was significantly higher in the GnRH agonist group than in the GnRH antagonist group (9 versus 1, p=0.022). The total number of oocytes retrieved, the number of metaphase II oocytes retrieved and the fertilization rate were similar in the two groups (p=0.602, p=0.621 and p=0.946). Clinical pregnancy rate per initiated cycle was similar in the the two groups (p=0.457); live birth rate per initiated cycle was 23.6% in the antagonist group and 26.4% in the agonist group (p=0.700).CONCLUSION: When compared with the GnRH agonist protocol, the flexible GnRh antagonist protocol is associated with a similar pregnancy rate with a reduction in the number of cycles cancelled because of the risk of OHSS. OBJECTIVE: To compare the flexible GnRH antagonist and the GnRH agonist long protocol in patients at high risk of OHSS undergoing IVF. DESIGN: Single-centre open label randomized prospective study. MATERIALS AND METHODS: The study included 144 women who had moderate or severe OHSS or had been at risk of OHSS during their first IVF/ICSI cycle with a mid-luteal long GnRH agonist plus gonadotrophin stimulation protocol. Patients were randomized to receive either cetrorelix 0.25 mg/day starting on day 3 of the menstrual cycle (antagonist group) or triptorelin 0.1 mg/day starting on day 21 of the menstrual cycle (agonist group). Ovarian stimulation was achieved with rFSH initiated on day 3 of the cycle at the maximal dose of 150 IU; the dose was adjusted depending on ovarian response. Embryo transfer was performed 2 or 3 days after oocyte retrieval. Luteal phase support was started on the day of oocyte retrieval using micronised progesterone vaginal gel. RESULTS: The two groups were similar in mean age, duration of infertility, body mass index, baseline FSH, total amount of rFSH administered and proportion of patients undergoing intracytoplasmic sperm injection. When oocyte maturation was triggered, the levels of E2 were lower in the antagonist group than in the agonist group (p<0.001). The number of cancelled cycles was significantly higher in the GnRH agonist group than in the GnRH antagonist group (9 versus 1, p=0.022). The total number of oocytes retrieved, the number of metaphase II oocytes retrieved and the fertilization rate were similar in the two groups (p=0.602, p=0.621 and p=0.946). Clinical pregnancy rate per initiated cycle was similar in the the two groups (p=0.457); live birth rate per initiated cycle was 23.6% in the antagonist group and 26.4% in the agonist group (p=0.700). CONCLUSION: When compared with the GnRH agonist protocol, the flexible GnRh antagonist protocol is associated with a similar pregnancy rate with a reduction in the number of cycles cancelled because of the risk of OHSS.

Assessment of theca cell function prior to controlled ovarian stimulation: the predictive value of serum basal/stimulated steroid levels

Serum androgen levels correlate with ovarian sensitivity to follicle-stimulating hormone (FSH) but in practice, standard baseline serum testosterone (T) levels prior to in-vitro fertilization (IVF) may not be the most appropriate marker for determination. Infertile women enrolled in an IVF programme were included in this study. Serum T and Delta4-androstenedione (A), and the androgen precursor 17-hydroxyprogesterone (17-OHP) were measured before and 24 h after a gonadotrophin-releasing hormone agonist stimulation test (GAST). An early follicular phase antral follicle count (AFC) was also performed. Patients were subsequently enrolled in a long gonadotrophin-releasing hormone agonist protocol with a standard FSH dose (150 IU) for 7 days to assess the association between androgen levels and ovarian responsiveness to FSH. The GAST elicited a significant increase in serum androgen levels that was well correlated with AFC. 17-OHP showed the greatest response to GAST and strongest correlation with AFC. The 17-OHP response to GAST differentiated patients with high ovarian reserve (OR) from those with low or normal OR as assessed by AFC, whereas only the estradiol response could differentiate those with low AFC. GAST-stimulated serum levels of 17-OHP were also correlated with ovarian response to FSH. Using receiver operating characteristic curve analysis, stimulated 17-OHP levels were predictive of the ovarian response to controlled ovarian stimulation, with similar power to that observed with AFC but lower power than with anti-Müllerian hormone. Serum androgen levels following GAST are correlated with AFC and ovarian response to FSH. Serum T is a less sensitive marker of theca cell function than 17-OHP.

A GnRH agonist and exogenous hormone stimulation protocol has a higher live-birth rate than a natural endogenous hormone protocol for frozen-thawed blastocyst-stage embryo transfer cycles: an analysis of 1391 cycles

To compare embryo and birth data in cryopreserved-thawed blastocyst-stage ET cycles between natural endogenous hormone cycles and exogenous hormone stimulation cycles. Retrospective cohort analysis. Large academic assisted reproductive technology center. One thousand three hundred ninety-one patient cycles undergoing frozen-thawed blastocyst-stage ET cycles. Live-birth rate. The synthetic protocol used GnRH agonist followed by estrogen and P. The natural protocol used monitoring and post-transfer P. The patients in the two protocols had similar baseline characteristics. Multiple linear regression showed the synthetic protocol to have a higher live-birth rate (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.02-2.09). In patients having two embryos transferred, the synthetic stimulation protocol resulted in a higher live-birth rate per cycle start (32.3% vs. 20.4%; relative risk [RR], 1.58; 95% CI, 1.22-2.06). Similarly, patients with one or two embryos transferred who had additional cryopreserved blastocysts available also had a higher live-birth rate per cycle start (36.1% vs. 12.1; RR, 2.98; 95% CI, 1.16-7.63). The synthetic hormone protocol was associated with a higher live-birth rate when compared with a natural cycle protocol for frozen-thawed blastocyst-stage ET cycles. This improvement persisted when analysis was controlled for cycle cancellation. The synthetic stimulation protocol for frozen-thawed embryo cycles offers improved outcome results for patients.

Frozen–thawed cleavage-stage embryo transfer cycles after previous GnRH agonist or antagonist stimulation

This study presents the results of fresh and frozen–thawed embryo transfers in women undergoing IVF with gonadotrophin-releasing hormone (GnRH) agonists and GnRH antagonists. By evaluating cycle outcomes, the impact of two different protocols on the endometrium was indirectly evaluated. For 714 women, embryos were frozen following day-3 fresh embryo transfer and the outcome of those fresh cycles (329 agonist cycles and 290 antagonist cycles) and subsequent frozen–thawed embryo transfer (91 agonist cycles and 104 antagonist cycles) were evaluated. Peak oestradiol concentrations of both groups were similar; however, significantly more oocytes were retrieved and more embryos frozen in the agonist versus antagonist group (both P = 0.0001). In fresh embryo transfer cycles, implantation and pregnancy rates in the agonist versus antagonist group were 42.3% versus 32.0% ( P = 0.0001) and 68.6% versus 58.2% ( P = 0.009) respectively. However, neither implantation or pregnancy rate significantly differed among frozen–thawed embryo transfer cycles between the two groups (21.4% versus 23.5% and 52.2% versus 52.4% respectively). These results suggest that ovarian stimulation parameter outcomes of GnRH antagonist cycles were not inferior to GnRH agonist cycles, therefore reduced embryo implantation and pregnancy rates in GnRH antagonist cycles can be attributable to possible deleterious effects on the endometrium.

Dynamic tests of ovarian reserve: a systematic review of diagnostic accuracy

Despite a plethora of tests of ovarian reserve, there is no perfect test to predict pregnancy. Recent evidence points that anti-Müllerian hormone and antral follicle count may be better than other tests, although other tests continue to be used and form the basis of exclusion of women from fertility treatments. This systematic review concentrated on dynamic tests of ovarian reserve [clomifene citrate challenge test (CCCT), gonadotrophin-releasing hormone agonist stimulation test (GAST) and exogenous FSH ovarian reserve test (EFORT)] and assessed their predictability in terms of fertility outcomes. The study did not restrict itself to women undergoing IVF. The diagnostic odds of abnormal CCCT for non-pregnancy were 2.11 (95% confidence interval, 1.04-4.29) at FSH >10 IU/l (day 3 or 10). The diagnostic accuracy of GAST and EFORT could not be determined due to inconsistencies in the way these tests were conducted. This systematic review and meta-analysis was limited by heterogeneity in terms of the population sampled and the index and reference tests. There is an urgent need for consensus on the performance of these tests and the definition of normality, if their use is to be continued. However, given the present level of evidence, these tests should be completely abandoned.

Low-dose aspirin in non-tubal IVF patients with previous failed conception: a prospective randomized double-blind placebo-controlled trial

To analyze whether the administration of low-dose aspirin during IVF treatment improves the uterine blood flow and improves ongoing pregnancy rates for non-tubal factor IVF patients with previous failed conception. Prospective double-blind placebo-controlled trial. University fertility clinic. Non-tubal IVF patients with previous failed conception. Daily 100 mg aspirin or placebo throughout an IVF treatment with a long GnRH-agonist stimulation protocol. Ongoing pregnancy rate, pulsatility index of the uterine artery. Of 169 patients, 84 were assigned to aspirin treatment and 85 to placebo treatment. In the aspirin group, 28 patients (35.4%) had an ongoing pregnancy, and in the placebo group, 26 patients (31.0%) had an ongoing pregnancy. Multilevel analyses showed that the pulsatility index of the uterine artery was not affected by aspirin or placebo treatment. Low-dose aspirin administration during IVF treatment does not improve pregnancy rates of non-tubal factor IVF patients with previous failed conception, and it does not affect the arterial uterine blood flow.

No room for cancellation, coasting, or ovarian hyperstimulation syndrome in oocyte donation cycles

We retrospectively studied 429 IVF donor cycles in which ovulation was triggered with either hCG (175 cycles) or GnRH agonist (254 cycles). Of the donors in whom ovulation was triggered with hCG, 3.2% developed symptoms of moderate (2.2%) or severe (1%) ovarian hyperstimulation syndrome, while none of the IVF donor cycles that were triggered with the GnRH agonist presented ovarian hyperstimulation syndrome, needed coasting, or were cancelled.

Effect of desogestrel and ethinyl estradiol pretreatment in superovulation cycles with short protocol

To study the effect of desogestrel and ethinyl estradiol (DEE) pre-treatment combined with gonadotropin releasing hormone agonist (GnRH-a) stimulation in in vitro fertilization-embryo transplantation (IVF-ET). A retrospective analysis was performed in 101 infertile women who received a short protocol of GnRH-a for IVF-ET treatment from June 2004 to June 2007 in the Reproductive Medicine Center of First Affiliated Hospital of Wenzhou Medical College. Patients had been pre-treated with oral contraceptive pill (OCP) for two months before GnRH-a combined with recombinant follicle stimulation hormone (r-FSH) treatment (study group, n = 42) or had not been pretreated with OCP (control group, n = 59). A statistical analysis of two groups was carried out for the assessment of ovulation stimulating effect of OCP and its influence on the IVF. Serum FSH was significantly decreased after OCP in the study group. Twelve pregnancies were obtained including 1 case of spontaneous abortion at 7 weeks in the study group, and 11 pregnancies were obtained including 2 cases of spontaneous abortion during 7 -9 weeks in control group. The clinical pregnancy rates in the study group (23%, 12/53) was higher than that in the control group (17%, 11/63), but the differences were not significant (P > 0.05). The miscarriage rate in the study group (8%, 1/12) was lower than that in the control group (18%, 2/11), however no significant differences were found between them (P > 0.05). The cycle cancellation rate in patients of the study group (5%, 3/56)was significantly lower than that in patients of the control group (17%, 13/76, P < 0.05). The differences between patients of the two groups with respect to age, basal level of FSH and luteinizing hormone (LH), antral follicle counts, the mean number of oocyte retrieval, the days of stimulation, total dose of r-FSH used, fertilization rate and embryo cleavage rate, however were insignificant. OCP pretreatment combined with short protocol of GnRH-a stimulation in IVF could significantly decrease the cycle cancellation rate, with a declining miscarriage rate and increasing pregnancy rate.

Prepubertal serum inhibin B in cryptorchid infants and in monorchid boys with compensatory testicular hypertrophy

To investigate the prepubertal serum inhibin B levels in monorchid boys with compensatory testicular hypertrophy (CTH) and in surgically treated cryptorchid boys with normal testicular volume. Prospective study. Pediatric Division, University of Verona, Italy. Thirty-two prepubertal boys: 11 monorchids with CTH and 21 cryptorchids. For comparison we analyzed 15 healthy boys. All patients underwent a GnRH agonist test. Inhibin B measurement was performed at basal time. There was a significant difference in mean testicular volume between monorchid and cryptorchid or healthy children, with boys with CTH evidencing larger testicle volume. There was no significant difference in inhibin B levels between boys with CTH and cryptorchid, but the levels were significantly lower in both groups than in the control group. Boys with CTH had significantly higher serum levels of basal FSH than children with cryptorchid. The FSH peak response to GnRH agonist stimulation was significantly higher in boys with CTH than in those with cryptorchid. Monorchid infants with CTH showed low inhibin B and high FSH levels. Our finding may confirm the hypothesis that CTH is unable to prevent testicular insufficiency in adulthood. We suggest an early hormonal evaluation of boys with CTH at puberty, together with early sperm analysis.

Hopes and facts about mild ovarian stimulation

Over the last two decades, easier and less expensive stimulation treatments have been largely replaced by more complex and more demanding protocols. Since the mid-nineties, long-term gonadotrophin-releasing hormone agonist stimulation protocols have been widely used. Such lengthy expensive regimens are not free from short- and long-term risks and complications. Mild stimulation protocols reduce the mean number of days of stimulation, the total amount of gonadotrophins used and the mean number of oocytes retrieved. The proportion of high quality and euploid embryos seems to be higher compared with conventional stimulation protocols and the pregnancy rate per embryo transfer is comparable. Moreover, the reduced costs, the better tolerability for patients and the less time needed to complete an IVF cycle make mild approaches clinically and cost-effective over a given period of time. However, further prospective randomized studies are needed to compare cumulative pregnancy rates between the two protocols. Natural cycle IVF, with minimal stimulation, has been recently proposed as an alternative to conventional stimulation protocols in normo- and poor responder patients. Although acceptable results have been reported, further large prospective randomized studies are needed to better evaluate the efficacy of these minimal regimens compared with conventional stimulation approaches.

A relative reduction in mid-follicular LH concentrations during GnRH agonist IVF/ICSI cycles leads to lower live birth rates

The effect of early- and mid-follicular LH concentrations on the ovarian response and pregnancy outcomes was evaluated in women receiving pituitary down-regulation with a GnRH agonist and ovarian stimulation with recombinant FSH (rFSH) during IVF/ICSI treatment. Blood samples were collected prospectively from 701 cycles (560 patients) of assisted reproduction and analysed retrospectively. On the basis of LH concentrations on stimulation day 7/8, the patients were divided into two groups: LH<1.2 IU/l (n=179) and LH>or=1.2 IU/l (n=522). Cycle outcomes were also compared on the basis of a ratio of mid- to early-follicular LH concentrations (<or=0.5, n=210; >0.5, n=491). Patients with low LH concentrations were found to have a significant reduction in the late-follicular estradiol concentrations (P<0.001), the number of oocytes retrieved (P<0.01) and the number of usable embryos (P<0.01), and they required significantly more rFSH (430 IU difference, P<0.01). These differences did not translate into a significant change in live birth rates. Conversely, a ratio of <or=0.5 mid- to early-follicular LH concentrations (a reduction of >or=50%) was associated with a significant reduction in live birth rates per embryo transfer and per cycle started (27.3 versus 19.0%, P<0.05 and 22.2 versus 15.8%, P<0.05, respectively). Low mid-follicular levels of LH have a significant impact on ovarian response but not on live birth rates. A fall in LH level of >or=50% from the early- to mid-follicular phase resulted in a lower live birth rate.