Low-dose Human Chorionic Gonadotropin Research Articles

Effect of GnRH agonist trigger with or without low-dose hCG on reproductive outcomes for PCOS women with freeze-all strategy: a propensity score matching study.

This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy. A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2mg GnRHa) and dual-trigger group (0.2mg GnRHa plus 1000/2000IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes. After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05). For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes.

The efficacy of GnRH agonist trigger followed by hCG add-back in normal responders for fresh embryo transfer: a case-control analysis from Vietnam

Aim: to assess the effects of a dual trigger by gonadotrophin-releasing hormone (GnRH) agonist and low-dose human chorionic gonadotropin (hCG) on in vitro fertilization (IVF) outcomes in women with normal ovarian response.Materials and Methods. This case-control analysis comprised 118 patients who responded normally to ovarian stimulation with a GnRH antagonist protocol at Hue Center for Reproductive Endocrinology and Infertility, Vietnam, between January 2018 and October 2019. Recruitment was achieved through case-control matching: a case (with Dual trigger – group A) was paired with control (with hCG trigger – group B) in a 1:1 ratio. The primary markers of success were the retrieval of oocytes and embryological data, the pregnancy rate, and the incidence of ovarian hyperstimulation syndrome (OHSS).Results. 59 patients in group A and 59 women in group B were recruited. Two groups had comparable patient characteristics and ovarian reserve. The initial dose, total dose, duration of gonadotropin administration, and peak of estradiol level were not statistically different across groups. The number of recovered oocytes (10.3 ± 4.2 vs. 10.0 ± 3.3; p = 0.663), mature oocytes (8.6 ± 3.7 vs.8.1 ± 2.8; p = 0.346), and high-quality embryos (56.2 ± 28.9 vs. 59.8 ± 35.9; p = 0.555) was equivalent. Fertilization, clinical pregnancy, and live birth rates were comparable between the dual trigger and hCG groups. In neither group were any occurrences of OHSS seen.Conclusion. Dual trigger may substitute hCG for final oocyte maturation and fresh embryo transfer in patients with normal responses to GnRH antagonist protocol-induced ovarian stimulation without compromising IVF outcomes.

P-682 Androgen and Inhibin B levels during ovarian stimulation before and after eight weeks of low dose hCG priming in women with low ovarian reserve

Abstract Study question Does eight weeks of low dose human chorionic gonadotropin (hCG)-priming affect androgen or Inhibin B levels in serum and follicular fluid during IVF/ICSI treatment? Summary answer Inhibin B was reduced on stimulation day 1 in the IVF/ICSI cycle following hCG-priming. Androgen levels in serum and follicular fluid was not increased. What is known already In our recently published pilot study, eight weeks of low-dose hCG-priming was used to stimulate the intraovarian androgen synthesis in women with AMH &amp;lt;6.29 pmol/L. Priming resulted in more retrieved oocytes and more follicles sized 2-5 mm and less sized 6-10 mm at the start of stimulation. Stimulation time and FSH consumption was increased after priming. HCG priming potentially stimulate the intraovarian androgen synthesis causing upregulation of FSH receptors on granulosa cells, and therefore it was unexpected that the antral follicles were smaller and stimulation time longer following priming. This might indicate a different mechanism of action than previously thought. Study design, size, duration A prospective, paired, non-blinded, single-center study including 20 women conducted between January 2021 and July 2021 at a tertiary referral hospital. Participants underwent two identical IVF treatments: a Control cycle including elective freezing of all blastocysts and a Study cycle with fresh blastocyst transfer. The Control and Study cycles were separated by eight weeks (two menstrual cycles) of hCG-priming by daily injections of 260 IE hCG (details in our previously published paper). Participants/materials, setting, methods Women aged 18-40 years with cycle lengths of 23-35 days and AMH &amp;lt;6.29 pmol/L. Control and Study IVF cycles were performed in a fixed GnRH-antagonist protocol. Blood samples were taken on stimulation day 1, stimulation day 5-6, trigger day, day of oocyte pick up (OPU), and trigger day + 7 days in the Control and Study cycles. Follicular fluid was collected from the first aspirated follicle on both sides during OPU in both cycles. Main results and the role of chance Inhibin B serum levels were significantly lower on stimulation day 1 after hCG-priming, but no other significant differences in serum Inhibin B or androgen levels were seen. The concentrations of Inhibin B and androstenedione in the follicular fluid from the Study and Control cycle did not vary but testosterone was significantly lower in the Study cycle. A lower Inhibin B in the Study cycle corresponds with the antral follicles being significantly smaller after priming, and this probably led to a longer stimulation time in the Study cycle. This contradicts the theory that androgen priming causes more FSH receptors on developing (antral up to preovulatory) follicles. Instead, we hypothesize that androgen priming rescued some small antral follicles that would have otherwise undergone atresia by the end of the previous menstrual cycle. The mechanism of action was likely an increase in androgen levels and FSH receptor expression within these small follicles, however, not enough to elevate androgen levels in serum. We retrieved significantly more oocytes in the Study cycle and the production of estradiol per follicle ≥10 mm on trigger day was comparable in the Study and Control cycle, suggesting that the rescued follicles were competent in producing oocytes and steroid hormones. Limitations, reasons for caution The sample size was small, and androgen and Inhibin B levels were not the primary outcome. We have not demonstrated a higher androgen level or FSH receptor expression in small antral follicles following hCG-priming. Wider implications of the findings The results make us question the mechanism of action behind hCG-priming prior to IVF. It is important to design a study with retrieval of small antral follicles immediately after priming to investigate the proposed hypothesis and to confirm improved cycle outcomes i.e., more retrieved oocytes in a larger study population. Trial registration number NCT04643925

Low-dose human chorionic gonadotropin supplementation initiated at the onset of ovarian stimulation can improve oocyte quality without impairing endometrial receptivity: Case series

Whether continuous low-dose human chorionic gonadotropin (hCG) supplementation during controlled ovarian hyperstimulation (COH) can improve oocyte and embryo quality is still controversial in clinical practice. We report the first case series of inadvertent COH in luteal-phase stimulation in the presence of endogenous or exogenous low-dose hCG. Patients were diagnosed with infertility. The first two cases had inadvertent COH during preexisting pregnancy, and one of which produced more high-quality embryos (5 vs 1) in the presence of low hCG. Both cases had a live birth. The third case had 7 repeated failures of IVF, during which a total of 55 oocytes were obtained, but only 3 developed into transferable embryo. However, supplementation of 330 IU hCG per day from the onset of COH resulted in the recovery of one high-quality embryo and subsequent delivery of a healthy baby following fresh embryo transfer in eighth attemption. In conclude, supplementation with low-dose hCG from the onset of ovarian stimulation can improve oocyte quality without impairing endometrial receptivity.

LUTEINIZING HORMONE SUPPLEMENTATION WITH HUMAN MENOPAUSAL GONADOTROPIN VERSUS LOW-DOSE HUMAN CHORIONIC GONADOTROPIN DURING STIMULATION DOES NOT AFFECT PREGNANCY OUTCOMES AFTER FRESH EMBRYO TRANSFER

To determine whether Luteinizing hormone (LH) supplementation with human Menopausal Gonadotropin (hMG) compared to low-dose human Chorionic Gonadotropin (LD-hCG) during controlled ovarian stimulation (COS) affects pregnancy outcomes after fresh embryo transfer (ET).

Gonadotrophin releasing hormone agonist with low dose human chorionic gonadotrophin co-triggers versus gonadotrophin releasing hormone agonist alone for reducing the risk of ovarian hyperstimulation in women with polycystic ovarian disease.

Gonadotrophin releasing hormone agonist with low dose human chorionic gonadotrophin co-triggers versus gonadotrophin releasing hormone agonist alone for reducing the risk of ovarian hyperstimulation in women with polycystic ovarian disease.

Gonadotropin receptor polymorphisms (FSHR N680S and LHCGR N312S) are not predictive of clinical outcome and live birth in assisted reproductive technology

To study the consequences of specific genotype profiles of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone choriogonadotropin receptor (LHCGR) on assisted reproductive technology outcomes when preimplantation genetic testing for aneuploidy is used for controlling the embryo ploidy status. The most common reported single-nucleotide polymorphisms in the amino acid position for the FSHR (N680S; N: asparagine, S: serine; [rs6166]) and the LHCGR (N312S variant; N: asparagine, S:serine [rs2293275]) were chosen for this study. Retrospective cohort study. Private Fertility Clinic. All women aged 18-40 years undergoing their first assisted reproductive technology cycle with aneuploidy screening between 2006 and 2017 with body mass index of >18 and <40 kg/m2 were included. All patients received both recombinant follicle-stimulating hormone and human menopausal gonadotropin or low dose human chorionic gonadotropin. Genomic DNA was isolated from patients' blood. Genotyping of the FSHR and LHCGR polymorphisms was performed using TaqMan genotyping assays. Associations between both receptor genotypes and clinical outcomes were assessed using generalized regression and ANOVA. Live birth rate was the primary outcome. Secondary outcomes included oocyte yield, mature oocytes, blastulation rate, usable blastocyst rate, and implantation rate. A total of 1,183 patients met the inclusion criteria and generated reliable genotype results. The overall genotype frequencies in the study population for the FSHR gene were as follows: 21.7% homozygous for S in codon 680, 29.2% homozygous for N680, and 48.1% heterozygous (N680S). As for the LHCGR, 15.6% were homozygous for N312, 38.5% homozygous for S312 and 45.9% heterozygous (N312S). Our study population consisted of 53.8% non-Hispanic white; 6.1% Hispanic white; 4.1% Afro-American; 15.4% Asian; and 20.6% other or unknown. No significant association was found with any of the studied variables (oocyte yield, usable blastocyst rate, implantation rate, live birth) when genotypes were analyzed per receptor or in combination with one another. There was a statistically significant but clinically irrelevant difference in the rate of mature oocytes across different variant combinations. Our findings suggest that the presence of gonadotropin receptor polymorphisms in both FSHR N680S and LHCGR N312S are not associated with assisted reproductive technology outcomes; therefore, these variants should not be considered reproductive predictors.

Effect of elevating luteinizing hormone action using low doses of human chorionic gonadotropin on double ovulation, follicle dynamics, and circulating follicle-stimulating hormone in lactating dairy cows

Double ovulation and twin pregnancy are undesirable traits in dairy cattle. Based on previous physiological observations, we tested the hypothesis that increased LH action [low-dose human chorionic gonadotropin (hCG)] before the expected time of diameter deviation would change circulating FSH concentrations, maximum size of the second largest (F2) and third largest (F3) follicles, and frequency of multiple ovulations in lactating dairy cows with minimal progesterone (P4) concentrations. In replicate 1, multiparous, nonbred lactating Holstein dairy cows (n = 18) had ovulation synchronized. On d 5 after ovulation, all cows had their corpus luteum regressed and were submitted to follicle (≥3 mm) aspiration 24 h later to induce emergence of a new follicular wave. Cows were then randomized to NoP4 (untreated) and NoP4+hCG (100 IU of hCG every 24 h for 4 d after follicle aspiration). Ultrasound evaluations and blood sample collections were performed every 12 h for 7 d after follicle aspiration. All cows were then treated with 200 μg of GnRH to induce ovulation. In replicate 2, cows (n = 16) were resubmitted to similar procedures (i.e., corpus luteum regression, follicle aspiration, randomization, ultrasound evaluations every 12 h, GnRH 7 d after aspiration). However, cows in replicate 2 received an intravaginal P4 device that had been previously used (∼18 d). Only cows with single (n = 15) and double (n = 16) ovulations were used in the analysis. No significant differences were detected for frequency of double ovulation, follicle sizes, and FSH concentrations across replicates (NoP4 vs. LowP4 and NoP4+hCG vs. LowP4+hCG), so data were combined. Double ovulation was 40% for control cows with no hCG (CONT) and 62.5% with hCG (hCG). Double ovulation increased as the maximum size of F2 increased: <9.5 mm and 9.5-11.5 mm (7.7%) and ≥11.5 mm (94.1%). The hCG group had more cows with F2 > 11.5 (69%) than with 9.5 ≥ F2 ≤ 11.5 (25%) and F2 < 9.5 (6%). In agreement, F2 and F3 maximum size were larger in the hCG group, but FSH concentrations were lower after F1 > 8.5 mm compared with CONT. In contrast, FSH concentrations were greater before deviation (F1 closest value to 8.5 mm) in cows with double ovulations than in those with single ovulations, regardless of hCG treatment. In addition, time from aspiration to deviation was shorter in cows with double rather than single ovulation and in cows treated with hCG as a result of faster F1, F2, and F3 growth rates before diameter deviation. In conclusion, greater FSH and follicle growth before deviation seems to be a primary driver of greater frequency of double ovulation in lactating cows with low circulating P4. Moreover, the increase in follicle growth before deviation and in the maximum size of F2 during hCG treatment suggests that increased LH may also have a role in stimulating double ovulation.

Effect of GnRH agonist alone or combined with different low-dose hCG on cumulative live birth rate for high responders in GnRH antagonist cycles: a retrospective study

BackgroundThere is insufficient evidence regarding the impact of dual trigger on oocyte maturity and reproductive outcomes in high responders. Thus, we aimed to explore the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone or combined with different low-dose human chorionic gonadotropin (hCG) regimens on rates of oocyte maturation and cumulative live birth in high responders who underwent a freeze-all strategy in GnRH antagonist cycles.MethodsA total of 1343 cycles were divided into three groups according to different trigger protocols: group A received GnRHa 0.2 mg (n = 577), group B received GnRHa 0.2 mg and hCG 1000 IU (n = 403), and group C received GnRHa 0.2 mg and hCG 2000 IU (n = 363).ResultsThere were no significant differences in age, body mass index, and rates of oocyte maturation, fertilization, available embryo, and top-quality embryo among the groups. However, the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS) was significantly different among the three groups (0% in group A, 1.49% in group B, and 1.38% in group C). For the first frozen embryo transfer (FET) cycle, there were no significant differences in the number of transferred embryos and rates of implantation, clinical pregnancy, live birth, and early miscarriage among the three groups. Additionally, the cumulative ongoing pregnancy rate and cumulative live birth rate were not significantly different among the three groups. Similarly, there were no significant differences in gestational age, birth weight, birth height, and the proportion of low birth weight among subgroups stratified by singleton or twin.ConclusionsGnRHa trigger combined with low-dose hCG (1000 IU or 2000 IU) did not improve oocyte maturity and embryo quality and was still associated with an increased risk of moderate to severe OHSS. Therefore, for high responders treated with the freeze-all strategy, the single GnRHa trigger is recommended for final oocyte maturation, which can prevent the occurrence of moderate to severe OHSS and obtain satisfactory pregnancy and neonatal outcomes in subsequent FET cycles.

Does dual trigger with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin improves clinical outcomes in normal responders in gonadotropin-releasing hormone (GnRH) antagonist IVF-ICSI Cycles

Does dual trigger with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin improves clinical outcomes in normal responders in gonadotropin-releasing hormone (GnRH) antagonist IVF-ICSI Cycles

Ovarian hyperstimulation syndrome following the use of GnRH agonist trigger of final oocyte maturation and freeze-all strategy: A case report and review of the literature

Rationale: The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin (hCG) for luteal support as an explanation for the development of ovarian hyperstimulation syndrome, and this is because of the gap in the listing of the predisposing factors that put women at an increased risk of ovarian hyperstimulation syndrome.Patient concerns: A case of 25-year-old woman presented with abdominal pain, distention, dyspnea, and nausea with a 6.5 kg increase in weight from baseline. Ultrasonographic examination showed bilaterally enlarged multicystic ovaries after gonadotropin-releasing hormone (GnRH) agonist triggering and cycle segmentation with no hCG rescue administration.Diagnosis: Moderate/severe ovarian hyperstimulation syndrome. Interventions: The woman was admitted to the hospital for medical management of moderate/severe ovarian hyperstimulation syndrome, and pain management was advanced to patient-controlled anesthesia with the start of low molecular weight heparin. On day 2, albumin therapy followed by a furosemide chase was started due to an increase in abdominal girth. On day 1, Cabergoline was maintained, and on day 2 the GnRH antagonist Cetrorelix was started.Outcomes: The woman’s clinical condition improved, and a clinical pregnancy was eventually achieved during the first cryo-warmed blastocyst cycle.Lessons: Ovarian hyperstimulation syndrome can still happen even after the use of GnRH agonist and avoidance of hCG support. Segmentation of in vitro fertilization with complete avoidance of hCG for luteal support remains the best approach.

Adding Low Dose hCG to rFSH in GnRH Antagonist ICSI Cycles: A Randomized Controlled Trial

Inhibition of luteinizing hormone (LH) by gonadotropin releasing hormone (GnRH) antagonist may lead to suboptimal response during ovarian stimulation. In addition, several studies suggest that low level of LH is associated with lowered fertilization and implantation rate and increased early pregnancy loss rate. The aim of this study is to study the effect of adding low dose human chorionic gonadotropin (hCG - 200 IU), as an LH supplement, to recombinant follicle stimulating hormone (rFSH) in a GnRH antagonist cycles in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Sixty-three infertile women undergoing IVF were randomly divided into two groups. One group was stimulated with the conventional stimulation protocol (rFSH alone), while the second group received 200 IU hCG in addition to rFSH in the late follicular phase (hCG + rFSH). Both groups' results including pregnancy rate, total dose of rFSH required, duration of stimulation, endometrial thickness, oocytes and embryos characteristic, serum hormone levels (Testosterone, Estradiol, Progesterone, and LH) and level of epidermal growth factor (EGF) were compared. The results show that pregnancy rate among the group of women who received the low dose hCG was higher than those who did not receive hCG. However, this difference did not reach statistical significance. Furthermore, other cycle outcomes and hormonal values were comparable between the two stimulation protocols.

DOES DUAL TRIGGER WITH COMBINATION OF GONADOTROPIN-RELEASING HORMONE AGONIST AND LOW DOSE HUMAN CHORIONIC GONADOTROPIN IMPROVES CLINICAL OUTCOMES IN NORMAL RESPONDERS IN GnRH ANTAGONIST IVF-ICSI CYCLES

Clinical outcomes of dual trigger containing gonadotropin-releasing hormone agonist (GnRHa) and low dose human chorionic gonadotropin (hCG) compared with the standard dose of human chorionic gonadotropin (hCG) trigger for final oocyte maturation in normal responder patients in GnRH Antagonist IVF-ICSI Cycles. A single centre prospective randomized comparative study conducted at a tertiary care infertility centre , Akanksha IVF centre, Janakpuri, New Delhi from 1st March 2020 to 28th February 2021. 80 normal responder patients defined as women in age group 21 to 37 year, with serum AMH level >1.2 ng/ml to < 4ng/ml , with AFC (3- 8) per ovary who were to undergo controlled ovarian hyperstimulation (COH) for IVF-ICSI cycles, were randomized by a computer based program into 2 groups of 40 each. All the patients underwent ovarian stimulation with a starting dose of recombinant FSH with dosage 150-225 IU on D2 and the dosage were adjusted according to follicular monitoring After at least one follicle reached a size of 14mm , antagonist Inj Cetrorelix 0.25 mg started subcutaneously daily. When > 2 follicles reached the size of 18 mm final oocyte maturation was triggered by either dual trigger of Inj Leuprolide acetate 2 mg and low dose 2000 IU highly purified Inj. hCG subcutaneously in Group 1 or by standard trigger dose 10000 IU of highly purified inj hCG in Group2. Oocyte retrievals were performed 35 to 36 hours after the trigger. IVF-ICSI was performed in all cases. Day 3 fresh embryo transfers were performed for all cases (2 x 8cell embryos).The luteal phase support was with vaginal supplementation of 800 mg micronized progesterone. Serum beta hCG was performed after14 days of embryo transfer . Primary outcome measured was clinical pregnancy rate and secondary outcomes measured were: implantation rate, miscarriage rate, number of MII oocytes picked up, number of embryos formed, and risk of OHSS. In dual trigger , group 1 the clinical pregnancy rate (52.50% vs 47.50% ) and implantation rate (29.67% vs 26.08% ) were higher than in Group 2 , and but the difference was not statistically significant. Miscarriage rate was lesser in group 1 (14.28%) than in group 2 (15.78%) and it was also not statistically significant . There were higher number of MII oocytes picked up and higher number of embryos formed in group1/ dual trigger group (10.63+5.46 and 8.2+3.4 respectively ) than in group 2 (8.10+5.74 and 6.8+3.6 respectively) and this difference was statistically significant . No OHSS was reported in group 1/ dual trigger group. Though there was increased clinical pregnancy rate, implantation rate and a lesser miscarriage rate in dual trigger group1 for but it was statistically not significant .There was significant increase in MII oocytes and number of embryos formed (p value .0064 and .0 156 respectively) in the dual trigger group. There was also no risk of OHSS in dual trigger group.

نتایج بارداری بهروش لقاح خارج رحمی در تحریک با آگونیست آزاد کننده گنادوتروپین، گنادوتروپین جفتی انسان و یا گنادوتروپین جفتی انسان به همراه آگونیست آزادکننده گنادوتروپین در زنان نابارور؛ کارآزمایی بالینی تصادفی

Introduction: Human chorionic gonadotropin for the final maturation of eggs in the In-vitro fertilization cycle was associated with the possibility of a negative effect on endometrial acceptance, fetal quality and ovarian hyper stimulation syndrome. Replacing it with a gonadotropin-releasing hormone agonist to trigger final ovulation is expected to reduce these effects. Therefore, this study was performed with aim to evaluate the outcome of triggering in in vitro fertilization with antagonist protocol by gonadotropin-releasing hormone agonist, human chorionic gonadotropin simultaneously with human gonadotropin-releasing hormone agonist and human chorionic gonadotropin. Methods: In this randomized clinical trial study conducted in 2015 and 2016, women were divided into three random groups after preparing the follicles for triggering and ovum retrieval. One group received 0.2 mg of dipherline, the second group received 10,000 units of human chorionic gonadotropin and the other group received 0.2 mg of dipherline along with 1500 units of human chorionic gonadotropin. The number and quality of eggs and embryos were the outcomes of the study. Data were analyzed by SPSS software (version 17) and Leven tests and one-way analysis of variance. P < 0.05 was considered statistically significant. Results: The number of retrieved oocytes in the group receiving gonadotropin-releasing agonist was significantly higher than the other groups (p = 0.001). More embryos were produced in the gonadotropin-releasing hormone agonist group compared to the other two groups (p = 0.009). However, the number of high quality embryos produced in the groups was similar. Conclusion: The onset of final oocyte maturation with gonadotropin-releasing hormone agonist significantly increases the number of retrieved oocytes and obtained embryos. However, dual stimulation using low-dose human chorionic gonadotropin (IU1500) and gonadotropin-releasing hormone agonist did not alter quality of embryo compared to the standard dose of human chorionic gonadotropin (IU10000).

Randomized, Controlled Pilot Study of Low-Dose Human Chorionic Gonadotropin Administration Beginning From the Early Follicular Phase for Women With Polycystic Ovarian Syndrome Undergoing Ovarian Stimulation Using the Progesterone Protocol.

Purpose: To illustrate whether low-dose human chorionic gonadotropin (hCG) administration during the early follicular phase could reduce the number of large preovulatory follicles in women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation using the progesterone protocol.Methods: We performed a randomized, controlled pilot trial at a university-affiliated tertiary hospital. A total of 40 infertile women undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment with the freeze-all strategy were included. Human menopausal gonadotropin (hMG) and progesterone soft capsule 100 mg/d were added simultaneously beginning from menstrual cycle day 3 for all participants. Low-dose hCG (200 IU) was injected every 3 days in the study group from the first day of ovarian stimulation until trigger. The primary outcome was the number of large preovulatory follicles. Secondary outcomes included the incidence of ovarian hyperstimulation syndrome (OHSS); the number of oocytes retrieved, mature oocytes, and good-quality embryos; and clinical results after frozen-thawed embryo transfer (FET) cycles.Results: The study group had slightly more large preovulatory follicles than the control group (17.75 ± 10 vs. 13.2 ± 5.34; P > 0.05). None of the participants experienced severe OHSS. There were no statistically significant differences in the number of oocytes retrieved (15.9 ± 8.46 vs. 15.75 ± 6.96), mature oocytes (13.55 ± 6.56 vs. 13.4 ± 6.34), and good-quality embryos (5.5 ± 3.41 vs. 4.9 ± 2.99) between the two groups (P > 0.05). Clinical pregnancy rates (65.52 vs. 41.94%; P = 0.067) and live birth rates (48.28 vs. 35.48%; P = 0.315) per transfer following FET of the study group were higher than those of the control group, but without statistical significance.Conclusions: Administration of low-dose hCG from the early follicular phase for PCOS patients undergoing ovarian stimulation with progesterone protocol may lead to slightly more early preovulatory follicles and marginally, but not significantly, higher clinical pregnancy rates. A continuous trial should be performed to explore the effects of supplementation with different doses of hCG from the start of ovarian stimulation in PCOS patients using the progesterone protocol.Clinical Trial Registration: Chictr.org.cn, identifier: ChiCTR-IOR-15007165

Replacing HMG/FSH by low-dose HCG to complete corifollitropin alfa stimulation reduces cost per clinical pregnancy: a randomized pragmatic trial.

The cost of IVF treatment remains high, among other factors because of the medication needed for ovarian stimulation. This study investigated the effect of using low-dose human chorionic gonadotrophin (HCG) for the second phase of follicular maturation after corifollitropin alfa induction, to replace the more expensive, either recombinant or human menopausal gonadotrophin (HMG), on the cost of ovarian stimulation. One hundred and five patients were randomly divided into two groups: patients in the HCG group (n = 50) received low-dose HCG from Day 7 until the diameter of at least three follicles reached 17 mm or more, while patients in the FSH group (n = 55) received conventional ovarian stimulation with highly purified HMG injections. The clinical pregnancy rate in the HCG group was 38% higher than in the FSH group (number needed to treat, NNT = 13). The cost per pregnancy needed for ovarian stimulation was reduced from €4902 in the FSH group to €2684 in the HCG group. Hence, the cost of ovarian stimulation medication to obtain 10 pregnancies using the conventional FSH protocol is sufficient to attain 18 pregnancies when applying the low-dose HCG protocol. This study provides evidence that using HCG instead of HMG/FSH for ovarian stimulation results in a significant reduction in the cost of IVF with, at least, an equivalent pregnancy rate.

The impact of HCG in IVF Treatment: Does it depend on age or on protocol?

Objectiveto evaluate the effect of the addition of low dose human chorionic gonadotropin (hCG) to human menopausal gonadotropin (HMG) throughout the early follicular phase in controlled ovarian stimulation (COS) conducted with two difference regimens. Gonadotropin-releasing hormone (GnRH) antagonist and short GnRH-agonist protocol were applied in two in vitro fertilization (IVF) clinics. MethodsClinical study conducted during the period 2014–2016 in two IVF clinics in a cohort of 240 women. In the first group 1 (124 women), a GnRH antagonist protocol with HMG and addition of low dose (100IU/day) h CG was applied. The other group 2 consisted of 116 women who underwent a short GnRH- agonist protocol with HMG and addition of low dose (100IU/day) h CG. ResultsMultiple logistic regression analysis was performed. The group 2 found to be associated with greater number of follicles and oocytes. The pregnancy rates were 12.1% and 26.7% in group 1 and group 2, respectively (p=0.004). For patients over 40 years, the number of follicles and oocytes retrieved were significant higher in group 2.The pregnancy rate in group 2 was higher than in group 1 (21, 6% vs 5%, p=0.017). ConclusionsAdvanced age women are likely to achievepregnancy using the GnRH Short than GnRH antagonist, when HMG/hCG is used, while HMG–hCG gonadotropins have the same potentialas Recombinant follicle stimulating hormone (rFSH)–hCG used in GnRH short protocol.

Low dose human chorionic gonadotropin administration at the time of gonadotropin releasing-hormone agonist trigger versus 35\u2009h later in women at high risk of developing ovarian hyperstimulation syndrome \u2013 a prospective randomized double-blind clinical trial

BackgroundOvarian hyperstimulation syndrome remains a serious complication during in vitro fertilization cycles if high dose human chorionic gonadotropin (hCG) is used to trigger ovulation in high responder patients. Though much of this risk is mitigated with trigger using gonadotropin releasing-hormone (GnRH) agonist alone, it may result in lower birth rates. GnRH-agonist trigger and adjuvant low dose hCG has been proposed to improve birth rates, but timing of this hCG support to corpus luteum function has never been fully described. In this randomized, prospective trial, we explore differences in live birth rates and incidence of ovarian hyperstimulation syndrome (OHSS) in high-responder patients undergoing in vitro fertilization (IVF) receiving low dose hCG at the time of GnRH-agonist (dual trigger) or hCG adjuvant at the time of oocyte retrieval. Does the timing of hCG support make a difference?ResultsThirty-four subjects high-responder patients were randomized to receive low-dose hCG at the time of GnRH-agonist trigger (Group 1) and 37 received low-dose hCG at the time of oocyte retrieval (Group 2). There were no differences in the baseline characteristics and outcome of ovarian stimulation between the two groups. There were no differences in the live birth rates between Group 1 and Group 2 by intention-to-treat (14/34, 41.2% versus 21/37, 56.8%, p = 0.19) or per-protocol (14/26, 53.8% versus 19/31, 61.3%, p = 0.57) analyses. There was a slightly higher incidence of OHSS in Group 2 compared to Group 1 although the difference was not statistically significant (3/31, 9.7% versus 1/26, 3.8%). All the cases of OHSS in Group 2 were moderate while the one case of OHSS in Group 1 was mild.ConclusionsFor high responder patients receiving GnRH-agonist trigger, low dose hCG supplementation allowed high pregnancy rates after fresh embryo transfer, regardless of whether it was given at the time of trigger or at oocyte retrieval. Dual trigger may be preferable to reduce the risk of OHSS.

The Effect of Dual Trigger of Oocyte Maturation with Gonadotropin-Releasing Hormone Agonist and Low-Dose Human Chorionic Gonadotropin on Pregnancy Rate in Women at Risk of Ovarian Hyperstimulation Syndrome

Background: the purpose of this study was to compare rates of ovarian hyperstimulation syndrome (OHSS) and the pregnancy outcome after using gonadotropin-releasing hormone agonists (GnRHa) alone and GnRHa in combination with low-dose human chorionic gonadotropin (hCG, dual trigger) for final oocyte maturation in women undergoing controlled ovarian hyperstimulation (COH). Patients and Methods: the study included 150 female patients with high risk of OHSS occurrence who were allocated by the Computer-based randomization method into two groups with 75 patients in each arm, Group I received GnRHa trigger and Group II received dual trigger (GnRHa + low-dose (1500 IU) hCG trigger). Results: Our study showed that the incidence of OHSS was higher after dual trigger than GnRHa trigger but with no statistically significant difference (8.0 vs 1.33 %, p >0.05). There were 6 cases of OHSS developed with dual trigger group (Group II) (3 were mild early OHSS, 2 were moderate early and one case was severe late OHSS). In contrast, there was only one case of severe late OHSS seen in Group I. Conclusion: Dual trigger for final oocyte maturation using GnRHa and low-dose hCG is associated with increased the incidence of early OHSS compared to GnRH alone. However, dual trigger appears to be a safe approach with a satisfactory pregnancy outcome. Also, the dual trigger improves the oocyte maturation, the number of yield embryos and the quality of embryos.

The Effect of Dual Trigger of Oocyte Maturation with Gonadotropin-Releasing Hormone Agonist and Low-Dose Human Chorionic Gonadotropin on Pregnancy Rate in Women at Risk of Ovarian Hyperstimulation Syndrome

The Effect of Dual Trigger of Oocyte Maturation with Gonadotropin-Releasing Hormone Agonist and Low-Dose Human Chorionic Gonadotropin on Pregnancy Rate in Women at Risk of Ovarian Hyperstimulation Syndrome