Spontaneous Luteinizing Hormone Surge Research Articles

Natural cycle versus modified natural cycle for endometrial preparation in women undergoing frozen-thawed embryo transfer: An RCT.

Studies have evaluated different endometrial preparation methods, but the optimal frozen-thawed embryo transfer (FET) cycle strategy in terms of the in-vitro fertilization outcome is still debated. To compare the natural versus modified natural cycles for endometrial preparation in women undergoing FET. This study was designed as a randomized clinical trial, and it was performed at the Arash women's hospital between August 2016-2018. Hundred and forty eligible participants were enrolled in this study and were randomly divided into 2 groups by using the block randomization method, including true natural FET (n = 70) and modified natural FET (mNFET) (n = 70) cycles. Both groups were monitored for endometrial thickness and follicular size; simultaneously spontaneous luteinizing hormone surge using urinary luteinizing hormone testing kits. The mNFET group received 5000 IU of human chorionic gonadotropin injection to trigger final follicular maturation. Luteal support by vaginal progesterone (cyclogest 400 mg twice daily) was used in true natural FET from the day of transfer until the 10 wk of pregnancy. Chemical and clinical pregnancy and abortion rates were considered as the primary outcomes. There were no differences in the participants' baseline characteristics between groups. There was no difference in clinical pregnancy and abortion rate between groups, while the implantation rate was significantly higher in the mNFET group (29.2% vs. 17.6%; p = 0.036). The results demonstrated that both types of natural cycles were similar in pregnancy outcomes, while modified cycles might be associated with a higher implantation rate.

Frozen-thawed embryo transfer in modified natural cycles: a retrospective analysis of pregnancy outcomes in ovulatory women with vs. without spontaneous luteinizing hormone surge

BackgroundTiming of frozen embryo transfer (FET) in natural endometrial preparation cycles is often based on luteinizing hormone (LH) surge. However, some patients do not show spontaneous LH surge despite follicular maturation. The objective of this study was to evaluate the impact of spontaneous LH surge on pregnancy outcomes in modified natural cycles (mNC).MethodsThis retrospective analysis included 1897 FET cycles with modified natural endometrial preparation in normo-ovulatory women between January 1, 2015, to December 31, 2019, at our center: 920 cycles with spontaneous LH surge (≥ 20 IU/L) and 977 without. For cleavage embryos, FET was conducted 4 and 5 days after hCG injection in women with and without LH surge, respectively. For blastocysts, FET was conducted 6 and 7 days after hCG injection in women with and without LH surge, respectively. Multivariate regression was conducted to examine the factors associated with live birth.ResultsLive birth rate was 43.7% in patients with spontaneous LH surge vs. 43.8% in women without LH surge (P = 0.961). The two groups also had similar implantation rate (36.2% vs. 36.7%, P = 0.772), biochemical pregnancy rate (54.8% vs. 55.4%, P = 0.796) and clinical pregnancy rate (50.9% vs. 51.7%, P = 0.721). In multivariate regression, live birth was not associated with LH surge (aOR, 0.947, 95% CI, 0.769, 1.166).ConclusionPregnancy outcomes were similar in mNC-FET in cycles with vs. without spontaneous LH surge if FET timing is adjusted.

The Effect of Spontaneous LH Surges on Pregnancy Outcomes in Patients Undergoing Letrozole-HMG IUI: A Retrospective Analysis of 6,285 Cycles.

BackgroundTo date, no consensus has been reached on whether to wait for spontaneous luteinizing hormone (LH) surge to occur or to trigger ovulation regardless of the presence of an LH surge for achieving higher success rate in intrauterine insemination (IUI) cycles. Therefore, we hope to investigate the effect of the presence of a spontaneous LH surge on pregnancy outcomes in letrozole–human menopausal gonadotropin (LE-HMG) IUI cycles.MethodsIn this retrospective cohort study, a total of 6,285 LE-HMG IUI cycles were included between January 2010 and May 2021. Cycles were categorized into three groups: the trigger + LH surge group, the trigger only group, and the LH surge only group. The primary outcome measure was the clinical pregnancy rate. A logistic regression analysis was performed to explore other risk factors affecting the clinical pregnancy rate.ResultsNo significant differences were observed in biochemical pregnancy rate (P =0.640), clinical pregnancy rate (P =0.702), ongoing pregnancy rate (P =0.842), and live birth rate (P =0.951) among the three groups. The binary logistic regression analysis also confirmed that the existence of an LH surge was not associated with clinical pregnancy. There was a difference in ectopic pregnancy rates (P =0.045), but logistic regression showed that the presence of a spontaneous LH surge has no association with ectopic pregnancy. Nonetheless, patients with lead follicles within 18.1-20.0 mm/20.1-22.0 mm and a long duration of LE treatment were less likely to get ectopic pregnant compared with patients with 14.1-16.0 mm lead follicles and shorter LE treatment (OR: 0.142, 95% CI: 0.023–0.891, P =0.037; OR: 0.142, 95% CI: 0.022–0.903, P =0.039; OR: 0.445, 95% CI: 0.235–0.840, P = 0.013).ConclusionsThe presence of a spontaneous LH surge in triggered LE-HMG IUI cycles does not appear to improve pregnancy rates. Thus, we suggest that waiting for an LH surge to occur is not necessary in triggered LE-HMG IUI cycles.

Optogenetic Activation of Arcuate Kisspeptin Neurons Generates a Luteinizing Hormone Surge-Like Secretion in an Estradiol-Dependent Manner.

Traditionally, the anteroventral periventricular (AVPV) nucleus has been the brain area associated with luteinizing hormone (LH) surge secretion in rodents. However, the role of the other population of hypothalamic kisspeptin neurons, in the arcuate nucleus (ARC), has been less well characterized with respect to surge generation. Previous experiments have demonstrated ARC kisspeptin knockdown reduced the amplitude of LH surges, indicating that they have a role in surge amplification. The present study used an optogenetic approach to selectively stimulate ARC kisspeptin neurons and examine the effect on LH surges in mice with different hormonal administrations. LH level was monitored from 13:00 to 21:00 h, at 30-minute intervals. Intact Kiss-Cre female mice showed increased LH secretion during the stimulation period in addition to displaying a spontaneous LH surge around the time of lights off. In ovariectomized Kiss-Cre mice, optogenetic stimulation was followed by a surge-like secretion of LH immediately after the stimulation period. Ovariectomized Kiss-Cre mice with a low dose of 17β-estradiol (OVX+E) replacement displayed a surge-like increase in LH release during period of optic stimulation. No LH response to the optic stimulation was observed in OVX+E mice on the day of estradiol benzoate (EB) treatment (day 1). However, after administration of progesterone (day 2), all OVX+E+EB+P mice exhibited an LH surge during optic stimulation. A spontaneous LH surge also occurred in these mice at the expected time. Taken together, these results help to affirm the fact that ARC kisspeptin may have a novel amplificatory role in LH surge production, which is dependent on the gonadal steroid milieu.

P–629 Is spontaneous ovulation better than induced ovulation for frozen-thawed embryo transfer cycle?

Abstract Study question Between spontaneous ovulation (SPO) and induced ovulation (INO) comparing clinical pregnancy rate and ongoing pregnancy rate for frozen-thawed embryo transfer (FET) cycle, which is better? Summary answer Both spontaneous ovulation and induced ovulation protocols showed no significant difference in clinical pregnancy rates and ongoing pregnancy rates. What is known already Recent practice worldwide is moving towards elective freezing of all embryos and subsequent frozen-thawed transfer, both for a perceived higher pregnancy rate as well as the significant reduction of ovarian hyperstimulation. The timing of FET can be determined by either detecting the spontaneous Luteinizing Hormone surge (SPO group) or by the administration of hCG (INO group). There is still an ongoing debate to determine which is the best protocol for frozen-thawed embryo transfer in the non-hormone replacement therapy (non-HRT) cycle. Study design, size, duration This retrospective study included 500 FET cycles for patients who had regular menses between June 2017 and June 2020. The FET cycles were grouped by type as follows: SPO (n = 281) and INO (n = 219). The primary outcome was the clinical pregnancy rate and the secondary outcome was ongoing pregnancy rate. Ongoing pregnancy is defined as a viable intrauterine pregnancy at 12 weeks of gestation confirmed on an ultrasound scan. Participants/materials, setting, methods This study was conducted in a single IVF centre. Vitrification was used as the cryopreservation method. To standardize outcome measures, only patients having single blastocyst transfer and aged under 38 years old were included. The average age of the patient was 32.9. Gamete donation, embryo donation, pre-implantation testing and assisted hatching cycles were also excluded from the analysis. Categorical data were analysed using Chi-square test SPSS version 25. Main results and the role of chance Clinical pregnancy rate for SPO group was 54.8% (154/281) versus 52.9% (116/219) in INO group. Even though clinical pregnancy rate was higher in SPO group as compared to INO group, it did not reach significance level (ꭓ2 = 0.17, p = 0.68). As all patients had single blastocyst transferred, the implantation rate was the same as clinical pregnancy rate. Ongoing pregnancy rate was also found higher in SPO group as compared to INO group (135/281, 48.0% and 97/219, 44.3% respectively) but again failed to reach significance level (ꭓ2 = 0.70, p = 0.40). Limitations, reasons for caution The retrospective nature of the study and therefore, the analysis was not adjusted for confounding factors such as blastocyst grading, etiology of infertility, and ethnicity of patients. Wider implications of the findings: In natural cycle, both spontaneous ovulation and induced ovulation protocols had the same pregnancy outcomes for frozen-thawed embryo transfer. However, induced ovulation can facilitate in scheduling FET timing to avoid weekends and public holidays, if necessary. Trial registration number Not applicable

The impact of timing modified natural cycle frozen embryo transfer based on spontaneous luteinizing hormone surge.

To evaluate whether adjusting timing of modified natural cycle frozen embryo transfer (mNC-FET) 1day earlier in the setting of a spontaneous LH surge has an impact on pregnancy outcomes. This retrospective cohort study evaluated all mNC-FET with euploid blastocysts from May 1, 2016 to March 30, 2019, at a single academic institution. Standard protocol for mNC-FET included ultrasound monitoring and hCG trigger when the dominant follicle and endometrial lining were appropriately developed. Patients had serum LH, estradiol, and progesterone checked on day of trigger. If LH was ≥ 20 mIU/mL, trigger was given that day and FET was performed 6days after surge (LH/HCG+6), with the intent of transferring 5days after ovulation. If LH was < 20 mIU/mL, FET was performed 7days after trigger (hCG+7). Primary outcomes included clinical pregnancy and live birth rates. To account for correlation between cycles, a generalized estimating equation (GEE) method for multivariable logistic regression was used. Four hundred fifty-three mNC-FET cycles met inclusion criteria, of which 205 were in the LH/HCG+6 group and 248 were in the HCG+7 group. The overall clinical pregnancy rate was 64% and clinical miscarriage rate was 4.8%, with similar rates between the two groups. The overall live birth rate was 60.9% (61.0% in LH/HCG+6 group and 60.9% in HCG+7 group). After implementing GEE, the odds of CP (aOR 0.97, 95% CI [0.65-1.45], p = 0.88) and LB (aOR 0.98, 95% CI [0.67-1.45], p = 0.93) were similar in both groups. In our study cohort, mNC-FET based on LH/HCG+6 versus HCG+7 had similar pregnancy outcomes.

IUI AFTER LH SURGE: HOW SOON IS TOO SOON?

Intrauterine insemination (IUI) following ovulation induction (OI) or in a natural cycle is a first line treatment for many etiologies of infertility. The timing of IUI in relation to ovulation trigger or spontaneous luteinizing hormone (LH) surge, as well as the number of IUI attempts that should be made remains a subject of debate. Many patients prefer a single IUI, whether due to expense of treatment or feasibility of making it to an office appointment on short notice. Sperm can theoretically survive in the female reproductive tract for up to 72 hours.

Customized Frozen Embryo Transfer after Identification of the Receptivity Window with a Transcriptomic Approach Improves the Implantation and Live Birth Rates in Patients with Repeated Implantation Failure

The aim of this prospective study was to evaluate outcome benefits expected in repeated implantation failure (RIF) patients (n = 217) after customized embryo transfer based upon identification of the receptivity window by transcriptomic approach using the Win-Test. In this test, the expression of 11 endometrial genes known to be predictive of endometrial receptivity is assessed by RT-PCR in biopsies collected during the implantation window (6–9 days after the spontaneous luteinizing hormone surge during natural cycles, 5–9 days after progesterone administration during hormone replacement therapy cycles). Then, patients underwent either customized embryo transfer (cET, n = 157 patients) according to the Win-Test results or embryo transfer according to the classical procedure (control group, n = 60). Pregnancy and live birth rates were compared in the two groups. The Win-Test showed that in 78.5% of women, the receptivity window lasted less than 48 h, although it could be shorter (< 24 h, 9.5%) or longer (> 48 h, 12%). This highlighted that only in 20% of patients with RIF the endometrium would have been receptive if the classical embryo transfer protocol was followed. In the other 80% of patients, the receptivity window was delayed by 1–3 days relative to the classical timing. This suggests that implantation failure could be linked to inadequate timing of embryo transfer. In agreement, both implantation (22.7% vs. 7.2%) and live birth rates per patient (31.8% vs. 8.3%) were significantly higher in the cET group than in the control group. cET on the basis of the Win-Test results could be proposed to improve pregnancy and live birth rates.ClinicalTrials.gov ID: NCT04192396; December 5, 2019, retrospectively registered.

Clomiphene Citrate or Medroxyprogesterone Acetate with Human Menopausal Gonadotropin in Poor Responders during In vitro Fertilization/Intracytoplasmic Sperm Injection Treatments Combined with Embryo Cryopreservation?

Objective: This study aimed to compare the efficacy of clomiphene citrate (CC) with human menopausal gonadotropin (hMG) and that of medroxyprogesterone acetate (MPA) with hMG in poor responders defined according to the Bologna criteria. Methods: The data of patients with poor ovarian response (POR) according to the Bologna criteria from September 2016 to November 2017 were retrospectively reviewed. All participants received either CC + hMG or the progesterone-primed ovarian stimulation protocol (PPOS) protocol. Results: A total of 340 patients and 563 in vitro fertilization cycles were analyzed in this study. The incidence of spontaneous luteinizing hormone (LH) surge and the mean LH level on trigger day were significantly lower in the PPOS group than in the CC + HMG group (0.04% vs. 3.49% and 4.26 ± 3.59 vs. 9.38 ± 6.92 mIU/mL, respectively, P < 0.05); however, the incidence of premature ovulation was similar between the two groups. The number of viable embryos harvested was not statistically different between the two groups (1.7 ± 1.1 vs. 1.5 ± 0.8, P = 0.06). The mean dose and duration of hMG were significantly higher in the PPOS group than in the CC + hMG group (908.7 ± 556.6 vs. 177.9 ± 214.5 IU and 6.0 ± 3.4 vs. 1.2 ± 1.5 days, respectively, P < 0.05). However, the number of oocytes retrieved, number of metaphase II oocytes, and fertilization rate were comparable between the two groups. Conclusions: The CC with low-dose gonadotropin strategy was superior to the MPA with hMG protocol for POR.

Controlled ovulation of the dominant follicle using progestin in minimal stimulation in poor responders

BackgroundThe use of progestin (P) during ovarian stimulation is effective in blocking the luteinizing hormone (LH) surge in women with normal ovarian reserve, however, its effects have not been determined in poor responders. This study aimed to explore the follicular dynamics in P-primed minimal stimulation in poor responders.MethodsA total of 204 infertile women with diminished ovarian reserve were allocated into the medroxyprogesterone acetate (MPA) group or the natural-cycle control group in an alternating order. MPA (10 mg) was administered daily beginning from the early follicular phase and a low dose of hMG was added in the late follicular phase if the serum FSH level was lower than 8.0mIU/ml. When a dominant follicle reached maturity, triptorelin 100 μg and hCG 1000 IU were used for trigger, and oocytes were retrieved 34-36 h later.All viable embryos were cryopreserved for subsequent frozen embryo transfer. Natural cycle IVF was used as controls.ResultsCompared with the natural cycle group, the MPA group exhibited a larger pre-ovulatory follicle (18.7 ± 1.8 mm vs 17.2 ± 2.2 mm), a longer follicular phase (13.6 ± 3.6 days vs 12.3 ± 3.2 days), and higher peak oestradiol values (403.88 ± 167.16 vs 265.26 ± 122.16 pg/ml), while maintaining lower LH values (P < 0.05). The incidences of spontaneous LH surge and premature ovulation decreased significantly (1.0% vs 50%; 2% vs. 10.8%, respectively; P < 0.05). A greater number of oocytes and viable embryos were harvested from the MPA group than from the natural cycle group (P < 0.05). Moreover,the clinical pregnancy rate was slightly higher in the MPA group than in the natural cycle controls, but the difference was not significant (11.8% vs 5.9%, P > 0.05).ConclusionThis study supported the hypothesis that P-primed minimal stimulation achieved ovulation control of the dominant follicle and did not adversely affect the quality of oocytes in poor responders. Therefore, P-priming is a promising approach to overcome premature ovulation in minimal stimulation for poor responders.Trial registrationChiCTR-OCH-14004176. Registered on January 8, 2014.

Oocyte retrieval timing based on spontaneous luteinizing hormone surge during natural cycle in vitro fertilization treatment

To determine the efficiency of oocyte retrieval (OR) timing based on the occurrence of spontaneous LH surge during natural cycle IVF (ncIVF) treatment. Retrospective cohort study. The cohort was divided into five subgroups according to the presumed stage of spontaneous LH surge on scheduling day (1A: before onset; 1B: surge start; 2: ascending slope; 3: peak; and 4: descending slope). Private infertility clinic. Three hundred sixty-five infertile patients who underwent 1,138 ncIVF treatment cycles during 2008-2011. Drug-free ncIVF treatment. Rate of successfully retrieved, fertilized oocytes, cleaved embryos, and live births per scheduled oocyte retrieval. In 61% of the cycles OR was scheduled before or just at the start of the LH surge (groups 1A-1B), whereas in the remaining cases it was scheduled after the surge had already started (groups 2-4). The proportion of cycles with successfully recovered (range, 71%-86%), inseminated (range, 61%-78%), fertilized oocytes (range, 47%-68%), cleaved embryos (range, 45%-66%), and live births (range, 4.1%-9.2%) was not significantly different among subgroups. In ncIVF treatment OR timing based on the occurrence of spontaneous LH surge is feasible, yielding acceptable oocyte recovery, fertilization, and embryo cleavage rates. This strategy combined with a rapid and low-risk OR procedure permits the management of a large ncIVF program on a 7-days-per-week basis within working hours.

Prognosis factors of pregnancy after intrauterine insemination with the husband's sperm: conclusions of an analysis of 2,019 cycles

To identify the prognostic factors for pregnancy after intrauterine insemination with the husband's sperm (IUI-H). Retrospective study. A single university medical center. 851 couples, for 2,019 IUI-H cycles. After controlled ovarian stimulation, IUI-H performed 36 hours after ovulation triggering or 24 hours after a spontaneous luteinizing hormone (LH) surge. Clinical pregnancy rate per cycle (PR) and delivery rate per cycle (DR). The overall PR was 14.8% and DR 10.8%. Higher PR and DR were observed for patients presenting with ovulation disorders (particularly polycystic ovary syndrome) or with male infertility. Secondary infertility in the woman appeared to be a positive prognostic factor as did a basal follicle-stimulating hormone (FSH) level ≤ 7 IU/L and ovulation triggering over spontaneous LH rise. The other parameters influencing the results were the women's age, the number of mature follicles obtained (≥ 2), the endometrial thickness (10-11 mm), and the number of progressive motile spermatozoa inseminated (>1 million). In women aged ≤ 38 years, IUI-H should be considered as an option, particularly in cases of female infertility from ovulation disorders, in cases of a normal ovarian reserve, in cases of secondary infertility, or when ≥ 1 million progressive sperm are inseminated. Bifollicular stimulation is required. In other cases, in vitro fertilization should be discussed as the first-line treatment.

Effect of Ovulatory Follicle Size on Steroidogenic Capacity and Molecular Markers of Oocyte Competence prior to GnRH-Induced Ovulation in Nonlactating Beef Cows.

Gonadotropin releasing hormone (GnRH)-induced ovulation of small dominant follicles decreased pregnancy rates and increased late embryonic/fetal mortality in beef cows. Inadequate oocyte competence, as affected by the physiological status of the dominant follicle, is a potential explanation for the reduction in pregnancy rates and late embryonic/fetal survival. Molecular markers of oocyte competence in both the oocyte (i.e. inhibin beta A [INHBA], inhibin beta B [INHBB] and their binding protein follistatin [FST]) and the surrounding cumulus cells (cathepsins B [CTSB], S [CTSS], and Z [CTSZ]) have been reported. The objective was to examine the relationship between preovulatory follicle diameter, steroidogenic capacity of the preovulatory follicle, and the following measures of oocyte competence: relative abundance of FST, INHBA, and INHBB mRNA in the oocyte, relative abundance of cathepsin (CTSB, CTSS, CTSK, and CTSZ) mRNA in cumulus cells, and the fatty acid profile (total monounsaturated fatty acids, polyunsaturated fatty acids, and saturated fatty acids) in follicular fluid. Non-lactating beef cows (n = 40) were administered GnRH on d −9, prostaglandin F2a (PG) on d −2, and ovaries harvested 48 hr after PG administration (d 0). Blood samples were collected every 8 hr from PG until ovary collection to characterize serum concentrations of estradiol, progesterone, insulin like growth factor 1 (IGF1), and luteinizing hormone (LH). None of the animals had a spontaneous LH surge by the time of ovary collection. The dominant follicle was dissected from the stroma and the cumulus-oocyte complex retrieved along with the corresponding follicular fluid. Only data from cows (n = 16) that did not express estrus and that had an estrogenic follicle at harvest (estradiol to progesterone ratio = 1 in follicular fluid) were included in the simple linear regression analysis. Dominant follicle diameter ranged from 9 to 14 mm at 48 hr after PG and the correlation between dominant follicle size and serum estradiol and follicular fluid estradiol was 0.54 (P < 0.05) and 0.50 (P < 0.04), respectively. As dominant follicle diameter increased, oocyte mRNA abundance (n = 16) of FST (P < 0.02), INHBA (P < 0.01) and INHBB (P < 0.03) decreased. However, as dominant follicle diameter increased cumulus cells (n = 12) had lower mRNA abundance of CTSB (P < 0.04), and tended to have lower abundance of CTSZ (P < 0.07). Furthermore, as follicular fluid concentrations of estradiol increased, CTSS abundance increased (P < 0.04) and CTSZ abundance tended to decrease (P < 0.06). Fatty acid profiles of total monounsaturated fatty acids, polyunsaturated fatty acids, and saturated fatty acids were not affected by dominant follicle size. In summary, relative abundance of INHBA, INHBB and FST mRNA in the oocyte were all negatively correlated with follicle diameter 48 hr after PG. Furthermore, relative abundance of CTSB mRNA in the cumulus cells from the ooctyes collected was also negatively associated with follicle diameter. As follicular diameter increased there was a correlated increase in serum and intrafollicular estradiol at ovary collection, but no effect on total fatty acids. In conclusion, there was no compelling data from the study to indicate that larger dominant follicles contained more competent oocytes. Supported by USDA NRI grant 2006-35203-17284 from USDA-CSREES.

Dynamique de l’index de vascularisation et de flux dans la phase préovulatoire de l’hyperstimulation ovarienne contrôlée. Relation avec le taux de conception

ObjectivesTo study the evolution of subendometrial vascularization flow index (VFI) in controlled ovarian hyperstimulation (COH+IIU) cycles and compare its dynamic changes in pregnant and non pregnant women. Patients and methodsThis is a retrospective study on 61 couples. To determine the profile of IVF just before ovulation, patients had 3D-Power Doppler angiography (3D-PDA) in this precise preovulatory phase. ResultsWe observed a decreasing profile of VFI in 52% (32/61) of the main group cycles, in 45% (14/31) of the subgroup with spontaneous peak of LH (luteinizing hormone), and in 60% (18/30) of the hCG (human chorionic gonadotropin) trigger subgroup. There were ten conceptions, (10/61, 16.4%), including eight (8/32, 30%) that were associated with a decreasing profile of VFI versus two (2/29, 7%) that were associated with an increasing profile (NS). In the detection of LH peak subgroup, we observed five conceptions (5/14, 36%) associated with a decreasing profile versus one conception (1/17, 6%) associated with an increasing profile of VFI (OR: 8.3; confidence interval [CI] 95%: 0.8–444; P=0.06 in favor of a of decreasing VFI profile). In the hCG subgroup, there were three conceptions in the decreasing VFI profile (3/18, 17%) and one conception with increasing VFI (1/12, 17%, P=0.6). Discussion and conclusionIn controlled ovarian hyperstimulation, a decreasing VFI profile is more common compared to an increasing one. Such au profile seems to be associated with a higher conception rate in cycles with spontaneous LH surge.

Ovarian stimulation with FSH in the rat reduces proestrous GnRH-dependent LH secretion through a dual mechanism: Inhibition of LH synthesis and release

Administration of human follicle-stimulating hormone (hFSH) to female rats during diestrus phase attenuates the spontaneous luteinizing hormone (LH) surge in proestrous afternoon. The inhibition of LH secretion is associated with a decreased pituitary LH content in intact, but not in ovariectomized rats injected with 25 μg estradiol benzoate (EB). This suggests that the mechanism of action of the putative non-steroidal ovarian bioactive FSH-dependent gonadodotropin surge attenuating factor (GnSAF) might, in addition, involve a reduction in LH synthesis. The present experiments studied, in proestrous pituitaries, the effects of different doses of hFSH, with or without EB on: (i) basal and GnRH-stimulated LH release and GnRH self-priming, (ii) LHβ mRNA values, and (iii) LH content. Results showed that bioactive GnSAF reduced mainly GnRH self-priming, but also GnRH-stimulated LH secretion and pituitary LH content in a dose-dependent manner. GnSAF had no effect on basal LH secretion or pituitary LHβ mRNA values. EB increased pituitary sensitivity to GnRH in controls, and overcame the inhibitory effects of GnSAF after low doses of hFSH but not after 10 IU of hFSH. In contrast with the sensitizing action of EB on LH secretion, EB had no effect on pituitary LHβ mRNA content or LH protein. It is concluded that the putative GnSAF blunted the LH surge by reducing LH synthesis at post-transcriptional level and antagonizing the GnRH-dependent LH secretion and the sensitizing effect of estradiol to GnRH.

Time course of final oocyte maturation and ovulation in chub mackerelScomber japonicusinduced by hCG and GnRHa

The question of whether the ovulation and spawning time in chub mackerel Scomber japonicus is entrained by a circadian rhythm was raised by our previous experiments. Further questions were also raised about whether the time course of human chorionic gonadotropin (hCG)-induced final oocyte maturation (FOM) and ovulation reflected the natural time course induced by endogeneous pituitary gonadotropin (GtH). To address these questions, hCG and gonadotropin-releasing hormone analog (GnRHa) were administered at two ‘opposite’ times, 14:00 and 02:00 hours, and the time courses of FOM and ovulation were compared. When hCG was injected, ovulation occurred 33 h post-injection in both groups, regardless of the timing of the hCG injection. The timing of ovulation in chub mackerel depends on the timing of hCG injection, but apparently not on circadian rhythms. When GnRHa was injected, ovulation began at 36 h post-injection of GnRHa, regardless of the timing of injection. These results indicate that the time course of FOM and ovulation in the chub mackerel followed a similar pattern whether stimulated by hCG injection or spontaneous luteinizing hormone (LH) surge because GnRHa induces the secretion of endogenous GtH (primarily LH) from the fish pituitary. Thus, it is concluded that the time course of hCG-induced FOM and ovulation in chub mackerel follows the natural time course induced by endogenous pituitary LH.

Predictors of a spontaneous luteinizing hormone surge in controlled ovarian hyperstimulation cycles

Predictors of a spontaneous luteinizing hormone surge in controlled ovarian hyperstimulation cycles

Effects of a Low-dose Leuprorelin Long Protocol on the Ovarian Response and Cycle Outcome in IVF

Summary Objective The purpose of our study was to examine the effectiveness of a low-dose leuprolide long protocol in an in vitro fertilization (IVF) program. Materials and Methods This was a retrospective analysis of the Department of Obstetrics and Gynecology IVF database at Taichung Veterans General Hospital, where the records for all patients who had received the long protocol beginning with a gonadotropin-releasing hormone agonist (GnRH-a) in the mid-luteal phase or gonadotropins alone between January 1, 1996, and December 31, 1998, were reviewed. Results Patients received the low-dose GnRH-a protocol in 48 cycles (group 1), the standard-dose GnRH-a protocol in 37 cycles (group 2), and the gonadotropin-alone protocol in 96 cycles (group 3). There were no significant differences in terms of age, causes of infertility, or duration of infertility among the three groups. However, more patients in group 1 suffered from primary infertility. Responses to ovarian stimulation indicated that patients in both groups 1 and 2 required a higher gonadotropin dosage and a longer duration of stimulation compared with group 3. Group 1 patients had about the same preovulatory peak serum estradiol concentration and had similar numbers of retrieved oocytes compared to other patients, but required more stimulation days and higher total gonadotropin doses. Pregnancy rates were higher in both long-protocol groups (36.4%, 29.7%, and 22.9%, respectively), but differences did not reach statistical significance. There were also no significant differences in terms of abortion rates and multiple pregnancy rates. Furthermore, there was no spontaneous luteinizing hormone surge in group 1 or 2 patients. Conclusion The low-dose GnRH-a down-regulation protocol can be considered an alternative to the standard- dose protocol. However, more studies are needed to find the optimal GnRH-a dose for clinical IVF.

Presence of κ-opioid tone at the onset of the ovulatory luteinizing hormone surge in the proestrous rat

A decrease in endogenous opioid peptide inhibitory tone on the afternoon of proestrus is one event underlying generation of the ovulatory luteinizing hormone (LH) surge. Whether this disinhibition involves a complete loss of opioid suppression at the time of the LH surge is controversial. The objective of the present study was to determine whether a total loss specifically of the κ-opioid inhibitory component suppressing LH secretion occurs on proestrus at the onset of the LH surge. Proestrous rats were infused intraventricularly with either artificial cerebrospinal fluid (aCSF) or aCSF containing nor-binaltorphimine (nor-BNI), a selective κ-opioid receptor antagonist, from 15:30 or 16:30 h (the approximate onset time of the spontaneous LH surge) to 18:50 h. The LH surge in rats treated with nor-BNI beginning at 15:30 h started 0.5 h earlier than the spontaneous surge in aCSF controls, and had significantly higher plasma LH levels from 16:30 to 17:30 h. Nor-BNI administration begun at 16:30 h also produced an LH surge with more elevated plasma LH levels at 17:30 and 18:00 h than in aCSF-treated controls. These results demonstrate that significant amounts of κ-opioid tone are still present during the hours when the LH surge is initiated. Thus, a complete loss of κ-opioid inhibition is not required for the onset of the LH surge on proestrus.

Luteinizing hormone and luteinizing hormone-releasing hormone secretion is under locus coeruleus control in female rats

It has been suggested that norepinephrine (NE) from the locus coeruleus (LC) plays an important role in triggering the preovulatory surge of gonadotropins. This work intended to study the role of LC in luteinizing hormone (LH) secretion during the estrous cycle and in ovariectomized rats treated with estradiol and progesterone (OVXE 2P) and to correlate it with LH releasing hormone (LHRH) content in the medial preoptic area (MPOA) and median eminence (ME). Female rats on each day of the estrous cycle and OVXE 2P were submitted to jugular cannulation and LC electrolytic lesion or sham-operation, at 09:00 h. Blood samples were collected hourly from 11:00 to 18:00 h, when animals were decapitated and their brains removed to analyze LC lesion and punch out the MPOA and ME. Plasma LH levels and LHRH content of MPOA and ME were determined by radioimmunoassay. During metestrus, diestrus and estrus, LC lesion did not modify either LH plasma concentrations or LHRH content, but completely abolished the preovulatory LH surge during proestrus and the surge of OVXE 2P. These blockades were accompanied by an increased content of LHRH in the MPOA and ME. The results suggest that: (1) LC does not participate in the control of basal LH secretion but its activation is essential to trigger spontaneous or induced LH surges, and (2) the increased content of LHRH in the MPOA and ME may be due to a decreased NE input to these areas. Thus, LC activation may be required for depolarization of LHRH neurons and consequent LH surges.