scholarly journals Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen

2021 ◽  
Vol 43 (10) ◽  
pp. 749-758
Author(s):  
Amanda Souza Setti ◽  
Daniela Paes de Almeida Ferreira Braga ◽  
Assumpto Iaconelli ◽  
Edson Borges
Keyword(s):  
Luteinizing Hormone ◽  
Ovarian Stimulation ◽  
Implantation Rate ◽  
Miscarriage Rate ◽  
Retrospective Case ◽  
High Quality ◽  
Oocyte Yield ◽  
Icsi Cycle ◽  
Icsi Outcomes ◽  
Estradiol Levels

Abstract Objective To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. Methods For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. Results Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. Conclusion Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

P–594 Ovarian stimulation with luteinizing hormone supplementation: the impact of timing on ovarian response and ICSI outcomes

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Iaconell ◽  
A Setti ◽  
D Braga ◽  
E Borge
Keyword(s):  
Luteinizing Hormone ◽  
Sample Size ◽  
Ovarian Stimulation ◽  
Gnrh Antagonist ◽  
Implantation Rate ◽  
Ovarian Response ◽  
Follicular Phase ◽  
Blastocyst Development ◽  
Normal Response ◽  
Icsi Outcomes

Abstract Study question Is there an impact of recombinant luteinizing-hormone (rLH) administration timing during controlled ovarian stimulation (COS) on ovarian response and intracytoplasmic sperm injection (ICSI) cycles outcomes? Summary answer rLH supplementation in patients with poor ovarian response (POR) improves laboratorial and clinical outcomes when started in the mid-follicular phase, in GnRH antagonist ICSI cycles. What is known already Meta-analyses demonstrated that the use of rLH combined with rFSH for COS may lead to more ongoing pregnancies than rFSH alone. However, there is limited evidence that the timing of rLH addition to rFSH may impact the ovarian response or the outcomes of ICSI, based on a limited casuistic, which demonstrated improved ovarian response, embryo quality and pregnancy rate with LH supplementation from GnRH antagonist administration day, in estimated POR patients. The objective of the present study was to further investigate this hypothesis in a larger population, and in subpopulations of patients stratified by age and response to COS. Study design, size, duration This historical cohort study included data obtained via chart review of 1278 ICSI cycles performed in 1278 patients between 2015 and 2018, in a private university-affiliated in vitro fertilization center. Post hoc power analysis was calculated, given α of 5%, sample size of 1278, and effect size for implantation rate. The achieved power was superior to 99%. Participants/materials, setting, methods Two groups were formed according to timing of LH administration: Group LH-start (n = 323), in which LH was started on day–1; and Group LH-mid (n = 955), in which LH was started with GnRH antagonist. Then, data were stratified according to female age (&lt;35 years-old, n = 283, and ≥35 years-old, n = 995) and response to COS (poor response (POR): ≤4 retrieved oocytes, n = 423, and normal response: &gt;5 retrieved oocytes, n = 855). Ovarian response and ICSI outcomes were compared among the groups. Main results and the role of chance In POR patients, significantly higher fertilization rate (68.3% ± 2.5 vs. 78.6% ± 3.7, p = 0.023), blastocyst development rate (22.5% ± 7.2 vs. 44.7% ± 6.2, p = 0.022) and implantation rate (17.6% ± 59.1 vs. 20.2% ± 43.2, p &lt; 0.001) were observed in Group LH-mid, even though the amount of LH used in these patients was not significant different from that used in Group LH-mid from patients with normal response to COS (1062.35 IU ± 54.33 vs. 925.81 IU ± 414.41, p: 0.431, respectively). For the general group and in patients aged ≥ 35 years, higher blastocyst development rates were observed in Group LH-mid compared to Group LH-start (33.0% ± 31.9 vs. 40.8% ± 32.6, p = 0.012, and 28.8% ± 30.4 vs 38.5% ± 32.3, p = 0.006, respectively). In patients aged &lt; 35 years and in those with normal response to COS, similar outcomes were obtained irrespective of timing of LH administration. Limitations, reasons for caution The limitations included the retrospective design and limited sample size in subpopulations. In addition, the reduced clinical outcomes related to POR patients may hamper the true estimation of the differences between the stimulation groups in terms of pregnancy and miscarriage rates. Wider implications of the findings: In POR patients, mid-follicular phase LH supplementation starting with 150 IU daily doses, may rescue the ongoing cycle by compensating an initial slow response, and balancing the deprivation of endogenous LH in GnRH antagonist cycles, with no need of expending more gonadotropin compared to patients with normal response to COS. Trial registration number Not applicable

scholarly journals Does daily co administration of gonadotropins and letrozole during the ovarian stimulation improve IVF outcome for poor and sub optimal responders?

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Moran Shapira ◽  
Raoul Orvieto ◽  
Oshrit Lebovitz ◽  
Ravit Nahum ◽  
Adva Aizer ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Multiple Dose ◽  
Paired Comparison ◽  
Ovarian Response ◽  
Clinical Pregnancy ◽  
Poor Responders ◽  
Ivf Outcomes ◽  
Oocyte Yield ◽  
Subsequent Cycle ◽  
Estradiol Levels

Abstract Background Co-administration of letrozole during the first 5 days of ovarian stimulation was suggested to improve IVF outcomes in poor responders. We aimed to determine whether poor/sub-optimal responders might benefit from Letrozole co-treatment throughout the entire stimulation course. Methods We retrospectively reviewed the medical files of women who demonstrated poor (oocyte yield ≤3) and sub-optimal (4 ≤ oocyte yield ≤9) ovarian response during conventional multiple-dose antagonist stimulation protocols and were co-treated in a subsequent cycle with 5 mg Letrozole from the first day of stimulation until trigger day. A self-paired comparison between gonadotropins-only and gonadotropins-letrozole cycles was performed. Results Twenty-four patients were included. Mean patients’ age was 39.83 ± 4.60 and mean day-3-FSH was 12.77 ± 4.49 IU/m. Duration of stimulation and total gonadotropins dose were comparable between the two cycle groups. Peak estradiol levels were significantly lower in gonadotropins-letrozole cycles (2786.74 ± 2118.53 vs 1200.13 ± 535.98, p < 0.05). Number of retrieved oocytes (3.29 ± 2.15 vs 6.46 ± 3.20, p < 0.05), MII-oocytes (2.47 ± 1.65 vs 5.59 ± 3.20, p < 0.05), 2PN-embryos (1.78 ± 1.50, 4.04 ± 2.74, p < 0.05) and top-quality embryos (0.91 ± 0.97 vs. 2.35 ± 1.66, p < 0.05) were significantly higher in the gonadotropins-letrozole cycles. Clinical pregnancy rate in gonadotropins-letrozole cycles was 31.5%. Conclusion Letrozole co-treatment during the entire stimulation course improves ovarian response and IVF outcomes in poor/sub-optimal responders.

P–678 Increased luteinizing hormone in ovarian dysfunction attenuates follicle development and oocyte quality in human

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Tanaka ◽  
K Kawamura
Keyword(s):  
Luteinizing Hormone ◽  
Ovarian Stimulation ◽  
Follicular Development ◽  
Oocyte Quality ◽  
Follicle Development ◽  
Follicle Growth ◽  
Ovarian Dysfunction ◽  
High Quality ◽  
Group A ◽  
Group B

Abstract Study question Can increased luteinizing hormone impair follicular development and oocyte quality in patients with ovarian dysfunction? Summary answer Increased luteinizing hormone attenuates follicular development and oocyte quality, resulting in arrest of follicle growth and empty follicles and low-quality embryos. What is known already Patients with ovarian dysfunction exhibit elevated gonadotropins and low estrogen levels reflecting their low ovarian reserve. For ovarian stimulation in these patients, natural or mild stimulation protocols are likely used, but we often experienced the arrest of follicle growth and empty follicles at oocyte retrieval. Animal studies demonstrated that chronic high LH exposure impaired the growth of antral follicles by suppressing the expression of FSHR in granulosa cells via a modulation of intraovarian regulators, including the LH-induced thecal factors. Study design, size, duration: Retrospective analysis was conducted in 72 patients with ovarian dysfunction who received ovarian stimulations followed by IVF-ET from April 2018 to March 2020 after obtaining written informed consents under an approval from the ethical committee of our hospital. Participants/materials, setting, methods The data of hormonal levels, transvaginal ultrasound during ovarian stimulation and clinical outcome of IVF were extracted from electric chart. For evaluation of embryo, high quality embryos referred to embryos having Veeck classification &gt;grade 3 and &gt;4 blastomeres. Statistical significance was determined using Dunnett or chi-square tests, with P &lt; 0.05 being statistically significant. Main results and the role of chance The median age of participants was 42 years of age (range 26–49) with low serum AMH levels (median 0.9 ng/ml, range 0–1.83). We analyzed 361 cycles of ovarian stimulation in total (median 4 cycles/patient, range 1–21). These stimulation cycles were classified into 3 groups; group A (n = 230): normal LH level, group B (n = 93): elevated LH level (&gt; 10 mIU/ml) after ovarian stimulation and group C (n = 33): elevated LH level from the initiation of ovarian stimulation. Among 361 cycles, the arrest of follicle growth was detected in 5 cycles (group A: 0%, group B: 60%, group C: 40%). The proportions of empty follicle in group A, B and C were 17.3±2.0%, 20.9±3.3%and 38.6±7.2%, respectively. The rate of empty follicle was significantly high in group C. Although there was no significant difference in the rates of oocyte degeneration and fertilization, the rate of high-quality embryos in group C was 0.8-fold lower than that of group A. Limitations, reasons for caution Due to limitation of participants, we could not determine the appropriate LH level for ovarian stimulation in patients with ovarian dysfunction based on receiver operatorating characteristic curve. Wider implications of the findings: Normalization of LH levels for ovarian simulation in patients with ovarian dysfunction could improve follicle development and oocyte quality. Trial registration number Not applicable

scholarly journals Dual trigger improves response to ovarian stimulation and ICSI outcomes in patients with a previous r-hCG triggered ICSI cycle

2021 ◽  
Author(s):  
Amanda Souza Setti ◽  
Luis Guilherme Louzada Maldonado ◽  
Daniela Paes de Almeida Ferreira Braga ◽  
Assumpto Iaconelli Júnior ◽  
Edson Borges Júnior
Keyword(s):  
Ovarian Stimulation ◽  
Icsi Cycle ◽  
Icsi Outcomes

P–757 The risk of aspirin and prednisone using in women with antithyroid antibodies undergoing assisted reproductive technology

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Xie ◽  
P Zhou ◽  
Y Yu ◽  
J Chen ◽  
L Zhou ◽  
...  
Keyword(s):  
Assisted Reproductive Technology ◽  
Implantation Rate ◽  
Fertilization Rate ◽  
Reproductive Technology ◽  
Clinical Pregnancy ◽  
Miscarriage Rate ◽  
Cleavage Rate ◽  
High Quality ◽  
Antithyroid Antibodies ◽  
Blastulation Rate

Abstract Study question Is it safe using aspirin (A) and prednisone (P) before pregnancy among women with antithyroid antibodies (ATAbs) undergoing assisted reproductive technology? Summary answer Combination therapy of aspirin and prednisone didn’t improve likelihood of clinical pregnancy, but increased miscarriage rate. What is known already Compared with women with negative-ATAb, women with positive-ATAb had a lower live birth rate and a higher miscarriage rate. Insufficient evidence existed to determine whether aspirin and prednisone therapy improved the success of pregnancy following assisted reproductive technology (ART) in ATAb-positive euthyroid women. Aspirin and prednisone were used frequently in clinical practice, but the use of these medicines before pregnancy during ART process is still controversial, and the risks of these medicines were not well understood. Study design, size, duration A prospective study involving 268 women with unexplained reason for infertility who tested positive for antithyroperoxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb) were being treated for infertility at the Second Affiliated Hospital of Zhejiang University School of Medicine, Ningbo Women and Children’s Hospital and People’s Hospital of Jinhua from October 2017 to July 2020. Their TSH level ranged from 0.35–4.0mIU/ml and they all underwent fresh embryo transfer. Participants/materials, setting, methods Overall, a total of 268 ATAb-positive women were divided 2 groups: group A: no treatment; B: A+P. Both medicines were used in the lowest effective dose. Between the two groups, we measured oocytes retrieved, fertilization rate, high-quality embryo rate, blastulation rate, cleavage rate,implantation rate, likelihood of clinical pregnancy and miscarriage rate. Kruskal-Wallis test was used in nonnormally distributed variables, and the χ2 test or Fisher exact test was used to compare categorical variables. Main results and the role of chance A total of 268 infertile women with unexplained reason who tested positive for TPOAb and/or TgAb were recruited in our study. According to assignment, they were divided into two groups. All women in different groups had the similar age, BMI, number of miscarriage and duration of infertility. Levels of FSH, AMH, TSH, FT4, FT3, fibrinogen and d-dimer were similar in all groups. The use of A+P reduced cleavage rate (F = 23.982, P &lt; 0.001) and implantation rate (F = 4.388, P = 0.036). The fertilization rate (P = 0.407), high-quality embryo rate (P = 0.208) and blastulation rate (P = 0.157) were not influenced by the use of medication. In this study, likelihood of clinical pregnancy (P = 0.066) did not change significantly after therapy, and miscarriage rate (P = 0.042) increased after medical treatment. Limitations, reasons for caution Firstly, Aspirin is just one representation of anticoagulation therapy, so additional consideration of low molecular heparin should also be considered. Secondly, further randomized controlled trials of aspirin and prednisone alone are needed. Wider implications of the findings: In this study, use of A+P showed no positive effect, and reduced cleavage rate and implantation rate, while increased miscarriage rate. So, the use of medication for interfile women should be cautious. Trial registration number n/a

scholarly journals Using Letrozole Cotreatment With Progestin-Primed Ovarian Stimulation In Women With Polycystic Ovary Syndrome Treated For IVF

2021 ◽  
Author(s):  
Yali Liu ◽  
Jiaying Lin ◽  
Li Chen ◽  
Xiaoyan Mao ◽  
Li Wang ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Ovarian Stimulation ◽  
Polycystic Ovary ◽  
Implantation Rate ◽  
Clinical Pregnancy ◽  
Control Group ◽  
Miscarriage Rate ◽  
Ovary Syndrome ◽  
Premature Lh Surge ◽  
Pituitary Suppression

Abstract Background: Women with polycystic ovary syndrome (PCOS) often experience poor oocyte quality and a high risk of ovarian hyperstimulation syndrome (OHSS) when treated with controlled ovarian stimulation (COS) in vitro fertilization (IVF). Progestin-primed ovarian stimulation (PPOS) shows good potential to compete with conventional protocols in women with PCOS. However, it always accompanied by increased pituitary suppression and gonadotropin consumption. Letrozole (LE) has the ability to increase luteinizing hormone (LH) levels and appears to have the potential to alleviate pituitary inhibition during COS in women with PCOS. A retrospective cohort trial was performed to evaluate the efficacy of PPOS with or without letrozole in infertile women with PCOS.Methods: This retrospective cohort study included 448 women with PCOS who underwent COS with human menopausal gonadotropin (hMG) and medroxyprogesterone acetate (MPA) (n=224) or hMG and MPA cotreatment with LE (n=224) from January 2018 to March 2021. Baseline characteristics of the two groups were balanced with propensity score matching using the nearest neighbour random matching algorithm at a ratio of 1:1. The primary outcome measure was the implantation rate. The secondary outcomes were the endocrinological profiles, gonadotropin dose and duration, number of oocytes retrieved and viable embryos, clinical pregnancy rate, miscarriage rate and ectopic pregnancy rates.Result(s): The implantation rate was significantly higher in the study group than that in the control group (42.22% vs. 34.69%, P < 0.05). Compared with the control group，the study group had a higher LH concentration on the trigger day (3.85±3.6 mIU/ml vs. 2.44±1.71 mIU/ml, P < 0.01), but there was no case of premature LH surge or OHSS in both groups. The consumption of gonadotropin, the number of oocytes retrieved and viable embryos were similar between the two groups. Additionally, no difference was found in the clinical pregnancy rate, miscarriage rate or ectopic pregnancy rate.Conclusion(s): This study shows that LE administration in the PPOS protocol was feasible to improve the implantation rate and alleviate profound pituitary suppression from progestin administration without interfering with its premature LH surge blockade effect but with a non-significant reduction in gonadotropin consumption in women with PCOS undergoing IVF treatment.

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