Ovulation Induction Protocols Research Articles

The progesterone prime protocol: an affordable option for ICSI in Egypt

BackgroundThe two main input indicators needed to assess the success of assisted reproductive technology (ART) strategies are cost-effectiveness and clinical outcome. Therefore, we focused in our study on the direct cost associated with the Progesterone Prime Ovulation Induction Protocol (P-P-OP protocol) compared to other protocols, and the clinical outcomes of this strategy were measured in their effect on implantation and pregnancy rates.MethodsA pilot single-armed study was conducted on 47 infertile women coming for an ICSI cycle. Progesterone priming was started with 10 mg dydrogesterone along with HMG 150–300 IU from the second day of the menstrual cycle and was maintained until the day of ovulation trigger. The primary outcome was the cost per cycle, while the secondary outcome was the clinical pregnancy rate. The cost per cycle, including the cryopreservation cost, was calculated for economic evaluation.ResultsPer each cycle, the number of retrieved oocytes was 14.87 ± 8.09, the number of mature oocytes was 9.81 ± 4.67, the number of total embryos was 8.74 ± 4.28 (grade A = 67.40%, grade B = 11.92%, grade C = 20.68%), and the number of transferred embryos was 2.43 ± 0.68. The clinical pregnancy rate in our study was 42.5%. Economically, the cost of the P-P-OP protocol for each patient was only 56 USD.ConclusionThe P-P-OP protocol is a simplified approach suitable for freeze-only strategies, offering the benefits of positive results, fewer injections, lower costs, and increased patient convenience.

Reproductive outcomes of prepubertal Bos indicus beef heifers raised in a pasture-based feeding system submitted to ovulation induction strategies prior to a timed-artificial insemination protocol

Reproductive outcomes were evaluated in Nelore (Bos indicus) heifers submitted to one, two or no ovulation induction protocols based on progesterone (P4) and estradiol (E2) prior to a timed-artificial insemination (TAI) protocol. A total of 1,437 heifers (13.0 ± 0.8 mo old; 3.1 ± 0.1 of body condition score [BCS] and 279.9 ± 25.8 kg of body weight [BW]) were randomly assigned to 1 of 3 treatments: 0IND (n = 486): no ovulation induction protocol; 1IND (n = 481): one ovulation induction protocol; or 2IND (n = 470): two ovulation induction protocols. On Day −47, heifers from 2IND received a disinfected intravaginal P4 device (2 g, previously used for 21 d), kept until Day −40, when 0.5 mg of E2 cypionate (EC) was given. On Day −19, heifers from 2IND and 1IND underwent the same protocol. On Day 0, all heifers were submitted to the same TAI protocol, starting with a P4 device (0.5 g), 0.5 mg of cloprostenol sodium (PGF), and 1.5 mg of E2 benzoate. On Day 7, P4 device was removed, 0.5 mg of PGF, 0.5 mg of EC, and 200 IU of equine chorionic gonadotropin (eCG) were administered. The TAI was performed 2 d later (Day 9). Blood samples were collected on Days −47 and 0, to determine the presence of CL (circulating P4 concentrations ≥ 1.0 ng/mL). Ultrasound was performed on Days 40, 75 and between Day 150 and parturition to assess pregnancy per AI (P/AI) and pregnancy loss (PL). Statistical analyses were performed using SAS 9.4 (a-cP ≤ 0.05; A,B0.05 < P ≤ 0.10). The proportion of heifers with CL on Day −47 was similar among groups (3.4%). A greater proportion of heifers from 1IND had CL on Day 0, followed by 2IND, then 0IND (87.9a; 80.4b; 28.8c%). There was an effect of treatment on expression of estrus (2IND: 66.6a; 1IND: 67.2a; 0IND: 57.4b%), P/AI on Day 40 (2IND: 53.4a; 1IND: 43.9b; 0IND: 46.5b%), P/AI on Day 75 (2IND: 49.8a; 1IND: 40.5b; 0IND: 44.4ab%) and final P/AI (2IND: 45.5a; 1IND: 35.8b; 0IND: 40.5ab%). No differences were observed in PL (40–75 = 6.3%; 75-final = 9.6%; Total = 15.3%). Particularly within lighter heifers, there was an effect of treatment on P/AI on Day 40 (0IND: 39.2b; 1IND: 43.3ab; 2IND: 53.9a%) and on Day 75 (0IND: 36.6B; 1IND: 39.0AB; 2IND: 48.5A%). At the first pregnancy diagnosis, more nonpregnant heifers from 2IND had CL on Day 40 than 0IND, but 1IND did not differ from the other groups (85.4a; 74.8b; 80.8ab%). In conclusion, ovulation induction protocols performed prior to the TAI protocol increased the proportion of heifers with CL on Day 0. The use of two induction protocols resulted in greater fertility, particularly in lighter heifers, and increased cyclicity among nonpregnant heifers. These results indicate that this strategy may be an optimized method for inducing cyclicity and enhancing fertility of prepubertal Nelore heifers raised in pasture-based feeding systems.

O-213 Analysis of risk factors for monozygotic twins following in vitro fertilization-embryo transfer

Abstract Study question To investigate the risk factors associated with the incidence of monozygotic twinning（MZT）following in vitro fertilization and embryo transfer (IVF-ET). Summary answer MZT following IVF-ET may be associated with a reduced endometrial thickness on the day of embryo transfer and a decrease in estradiol levels post-transfer. What is known already MZT pregnancy arises from the division of a single fertilized ovum, resulting in offspring with identical genetic material. These twins exhibit markedly higher rates of complications compared to dizygotic counterparts, including increased incidences of miscarriage, congenital anomalies, intrauterine fetal demise, growth restriction, and preterm delivery. The underlying biological processes leading to MZT remain elusive. Presently, scholarly discourse centers around two predominant models and one hypothesis: the zygote division model, the embryonic membrane fusion model, and the over-mature gametes hypothesis, respectively. IVF-ET has been implicated in the heightened occurrence of MZT, suggesting a potential iatrogenic element to this phenomenon. Study design, size, duration A retrospective cohort study has been conducted. We analyzed 582 IVF-ET cycles at a large teaching hospital from January 2007 to December 2022, including 291 clinically confirmed MZTs, and 291 matched non-MZTs. Participants/materials, setting, methods A total of 582 participants, 291 in both MZT group and non-MZT group. There were 146 fresh embryo transfer cycles and 145 frozen-thawed cycles in the MZT group. Each cycle type was matched on a 1:1 basis by age and embryo transfer date with a control group that did not result in MZT following IVF-ET. We examined the disparities between the MZT group and the non-MZT group, and performed the Logistics regression analysis. Main results and the role of chance Significant differences were observed in the MZT group compared to the non-MZT group in the fresh embryo transfer cycle, particularly regarding estradiol (E2) and progesterone (P) levels on day 7 post-transfer, E2/P ratios on day 14 post-transfer, and endometrial thickness on the day of transfer (p&amp;lt;0.05). Logistic regression analysis indicated a correlation between reduced endometrial thickness on the transfer day and the occurrence of MZT. During the frozen-thawed cycle, significant differences were noted in E2/P ratios, E2 levels on day 7 post-transfer, and endometrial thickness on embryo transfer day (p&amp;lt;0.05). Logistic regression analysis suggested that lower E2 levels on day 7 post-transfer and reduced endometrial thickness on embryo transfer day were predictive of MZT. Additional potential influencing factors included the duration of the participants’ menstrual cycle, the protocol of ovulation induction, and the duration of embryo culture in vitro. Limitations, reasons for caution Primarily, the retrospective design may introduce bias, notably due to the potential absence of comprehensive data. Secondly, the study is constrained by the sample size, with 146 fresh cycles and 145 frozen cycles, which may not provide a fully representative statistical power. Wider implications of the findings The incidence of MZT may implicate signaling pathways at the maternal-fetal interface, with early embryonic split potentially serving as a compensatory mechanism in response to suboptimal estrogen levels or diminished endometrial thickness, thus enhancing embryonic viability. Trial registration number not applicable

Follicle-Stimulating Hormone Receptor (FSHR) Ser680Asn Genotype Does Not Affect the Follicular Fluid Hormonal Profile in Stimulated Cycles Using Different Gonadotropin Preparations for Ovulation Induction: A Pilot Study.

The existing literature lacks consensus on the effectiveness of utilizing polymorphisms to enhance outcomes in in vitro fertilization (IVF), particularly regarding ovulation induction protocols, oocyte and embryo quality, and pregnancy rates. Therefore, the present pilot study aims to assess whether the composition of different gonadotropin preparations affects the ovarian stimulation protocol concerning follicle-stimulating hormone receptor (FSHR)Ser680Asn genotypes (Ser/Ser, Ser/Asn, and Asn/Asn), in terms of ovulation induction parameters, including oocyte maturation rate, embryo quality, and pregnancy rate. A total of 94 IVF patients underwent treatment using a GnRH antagonist protocol with four distinct gonadotropin preparations: HMG, HMG/hCG, rFSH, and rFSH/hCG. Follicular fluid (FF) samples were pooled for each patient for analysis. No statistical differences in the FFhormonal profile (progesterone, testosterone, androstenedione, estradiol, FSH, hCG) among the FSHR genotypes were reported either separately for each protocol or in combination for the four different preparations of gonadotropins. The maturation rate of MII oocytes and embryo quality did not differ among women carrying either Ser/Ser, Ser/Asn, or Asn/Asn genotype (p-value=0.475, and p-value=1.000, respectively). Moreover, no statistically significant correlation was revealed among Ser/Ser, Ser/Asn, and Asn/Asn carriers and pregnancy rate (p = 0.588). FF hormonal analysis of women undergoing IVF using different ovulation induction protocols and carrying either Ser/Ser, Ser/Asn, or Asn/Asn genotype revealed no significant correlations, in terms of maturation rate of MII oocytes, embryo quality, and pregnancy rate, indicating that the FSHR Ser680Asn genotype does not constitute a biomarker for a positive pregnancy outcome. Therefore, the existence of a different mechanism for the expression of FSHRSer680Asn genotypes in the FF hormonal profile related to stimulated cycles is implied.

Impact of repeated ovarian hyperstimulation on the reproductive function

One of six couples (17.5 % of the adult population) worldwide is affected by infertility during their lifetime. This number represents a substantial increase in the prevalence of this gynecological condition over the last decade. Ovulatory dysfunction and anovulation are the main causes of female infertility. Timed intercourse, intrauterine insemination, and assisted reproductive technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the most common interventions for infertile couples. Ovulation induction protocols for IVF/ICSI routinely use supraphysiological doses of gonadotropins to stimulate many preovulatory follicles. Animal and human studies suggested that ovarian hyperstimulation, alone or repeatedly, for ART cycles can induce changes in the immune response and increase the oxidative stress (OS) in the ovarian microenvironment. The consequences of repeated ovarian hyperstimulation on the human ovary remain poorly understood, particularly in relation to the effects of ovarian stimulation on the immune system and the potential for ovarian stimulation to cause OS. Animal studies have observed that repeated cycles of ovarian hyperstimulation can accelerate ovarian aging. Changes in ovarian hormone levels, accelerated loss of ovarian reserve, disorders in ovarian ultrastructure, ovarian senescence, and decreased reproductive performance represent possible long-term effects of repeated ovarian hyperstimulation. The short and long-term impact of the combination of antioxidant agents in ovarian hyperstimulation protocols in women undergoing ART must urgently be better understood. The recent increase in the number of ART and fertility preservation cycles may accelerate ovarian aging in these women, promoting consequences beyond the reproductive function and including health deterioration.

Induction of puberty vs. induction of ovulation using steroid hormones in beef heifers: a comprehensive review.

This review elucidates the physiological and endocrinological processes intrinsic to puberty and ovulation induction protocols in Bos indicus and Bos taurus beef heifers. Puberty is a complex physiological event involving gonadotropic and metabolic changes that lead to sexual maturity, first ovulation, and regular reproductive cycles, enabling females to reproduce. Exposure to progesterone-based hormonal protocols, with or without additional hormones, can reduce the age at first ovulation and improve sexual maturity through stimuli in the hypothalamus-pituitary-gonadal (HPG) axis and uterine development. However, inducing puberty differs from inducing ovulation, as it does not ensure the heifer will continue cycling or be ready to establish and maintain pregnancy after hormonal exposure. Regardless of the pharmacological basis, studies consistently report that beef heifers that had a corpus luteum (CL) prior to the timed-artificial insemination (TAI) protocol, have greater expression of estrus in response to synchronization and greater pregnancy per AI compared to heifers without a CL. The combination of P4 and E2 significantly impacts uterine development, increasing reproductive efficiency. Exposure to P4 causes a positive effect on inducing ovulation. However, studies indicate that the addition of E2 esters at the time of P4 device removal increases the ovulation rate. In general, the studies showed that fertility varied according to the type of the ovulation induction protocol used, but with inconsistent results. Although ovulation induction protocols are strategic tools to accelerate sexual maturity, a holistic view of the entire system is extremely important, combining integration with genetics and nutrition to enhance the reproductive outcomes of beef heifers. Future research is needed to understand and refine these protocols, driving the efficiency of beef cattle production systems.

Intrauterine insemination: prognostic factors.

To evaluate the impact of possible maternal and paternal prognostic factors and ovarian stimulation protocols on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles. Retrospective observational study of 341 IUI cycles performed from January 2016 to November 2020 at the Assisted Reproduction Service of the Clinics Hospital of the Ribeirão Preto Medical School, University of São Paulo. Clinical pregnancy and live birth rates and their potential prognostic factors were evaluated. Wilcoxon's non-parametric test was used to compare quantitative variables, and the chi-square test to compare qualitative variables, adopting a significance level of p<0.05. A logistic regression model was performed to verify which exploratory variables are predictive factors for pregnancy outcome. The ovulation induction protocol using gonadotropins plus letrozole (p=0.0097; OR 4.3286, CI 1.3040 - 14.3684) and post-capacitation progressive sperm ≥ 5million/mL (p=0.0253) showed a statistically significant correlation with the live birth rate. Female and male age, etiology of infertility, obesity, multifollicular growth, endometrial thickness ≥ 7 mm, and time between human chorionic gonadotropin administration and IUI performance were not associated with the primary outcomes. In the group of patients with ideal characteristics (women aged< 40 years, BMI < 30 kg/m2, antral follicle count ≥ 5, partner aged< 45 years, and post-capacitation semen with progressive spermatozoa ≥ 5 million/mL), the rate of clinical pregnancy was 14.8%, while that of live birth, 9.9%. In this study, the ovulation induction protocol with gonadotropins plus letrozole and post-capacitation progressive sperm ≥ 5 million/mL were the only variables that significantly correlated with intrauterine insemination success.

Baseline Scoring System: A Novel Way to Design Safe Ovulation Induction Protocols

Baseline Scoring System: A Novel Way to Design Safe Ovulation Induction Protocols

Optimising Ovulation Induction in PCOS

Biochemical, Metabolic and Endocrine changes in PCOS result in reproductive impairment in women with PCOS. Controlled ovarian stimulation (COS) may be associated with • Unpredictable response • Response may be slow • Hyper-response - OHSS • Risk of Cyst Formation • Poor oocyte quality • Miscarriage • Cycle cancellation So, the ovulation induction protocol should be efficacious and safe resulting in a singleton live birth, minimising complications, and risks like ovarian hyperstimulation syndrome (OHSS), multiple pregnancies and cancellation of cycles. For this special consideration should be given to prediction of response, pre-treatment, choosing the right ovulation induction (OI) protocol with right dose and analogue, using GnRH agonist trigger instead of hCG, preventing late follicular phase rise in progesterone, or following the segmentation protocol. We can maximize the success rates by stimulation individualization based on age, AMH, AFC and amended further for BMI. AMH is considered as more sensitive marker to define follicle excess than AFC as it appraises more follicle classes - preantral and early antral. One should probably use mild stimulation protocols where gonadotropins are given in combination with oral ovulogens or the low dose step up protocol. It is essential that we use GnRH antagonist protocol and administer GnRH agonist if there is risk of OHSS. If segmentation protocol is used one could also use the progesterone primed ovarian stimulation instead of GnRG antagonist. One could reduce the incidence of OHSS by laparoscopic ovarian drilling and use of Metformin and aspirin before assisted reproduction. If the patient is at risk of developing OHSS during stimulation then one could administer cabergoline, intravenous infusion of calcium gluconate or albumin and methylprednisolone. But freezing all embryos and transferring them in a subsequent cycle increase the efficacy and reduce complications of ART in PCOS women. Elective single embryo transfer(eSET) should be the norm to reduce the multiple pregnancy rate. Conclusion Thus, in all ART cycles individualised COS with freeze all and eSET could help in increasing the success of ART and reducing stress and anxiety and complications in these women.

Live birth rate following endometrial preparation with daily versus depot GnRH agonist

Background Gonadotrophin-releasing hormone agonist (GnRHa) downregulates gonadotropin secretion in the pituitary gland. It is used both in ovulation induction protocols and in artificial endometrium preparation. Frozen—thawed embryo transfer to artificially prepared endometrium (FET-APE) is a frequent procedure in vitro fertilization (IVF) which requires GnRHa. It can be used either as a daily low-dose injection or as a single depot injection. It is unclear which of these two regimens is superior for artificial endometrium preparation. Methods We evaluated the data of 72 patients who had undergone frozen embryo transfer following the 5th day Preimplantation Genetic Test-aneuploidy (PGT-A) between 2018–2021. All embryos were genetically screened, and euploid single embryos were transferred. Group 1 (n: 36) used depot GnRHa, and Group 2 (n: 36) used single daily injections for artificial endometrial preparation. The outcomes for Beta Human Chorionic Gonadotrophin (BHCG) positivity and live birth rates (LBR) was compared. Results The BHCG positivity for Group 1 and Group 2 was 75% and 80.6%, respectively. The LBR for Group 1 and Group 2 were found to be 58.3% and 63.9%, respectively. There was no statistically significant differences between the two groups. Conclusions In artificial endometrium preparation, depot GnRHa offers cheaper and more convenient alternative to single daily dose injections, particularly in busy clinical settings.

Successful delivery after in vitro fertilization-embryo transfer in a woman with metachronous primary cancer of ovary and endometrium: a case report

BackgroundThe appearance of malignancies at various times in the same individual, excluding metastases of the initial primary cancer, is termed multiple primary cancers. Double primary gynecological cancers cause inevitable damage to female reproductive function, and the preservation of fertility in such patients remains a challenging issue as relatively few cases have been reported. This case report provides management options for dual primary ovarian and endometrial cancers, including the choice of ovulation induction protocols, considerations during pregnancy and parturition, with the aim of providing assistance to clinicians.Case presentationWe report a case of a 39-year-old woman with primary infertility and a medical history of right-sided ovarian mucinous borderline tumor with intraepithelial carcinoma, left-sided ovarian mucinous cystadenoma and endometrial cancer, who successfully conceived with in vitro fertilization-embryo transfer (IVF-ET) after three different ovulation induction protocols. During her pregnancy, she was complicated by central placenta praevia with placental implantation and eventually delivered a healthy female infant by caesarean section at 33 gestational weeks.ConclusionsFor patients with double primary gynecological cancers who have an intense desire for fertility, the most appropriate oncological treatment should be applied according to the patient’s individual situation, and fertility preservation should be performed promptly. Ovulation induction protocol should be individualized and deliberate, with the aim of ensuring that the patient’s hormone levels do not precipitate a recurrence of the primary disease during induction of ovulation and maximizing fertility outcomes. In addition, the risk of postpartum hemorrhage due to placental factors cannot be neglected in such patients.

Analysis of cumulative live birth rate outcomes of three ovarian stimulation protocols in patients after laparoscopic cystectomy of ovarial endometrioma: a retrospective cohort study

BackgroundPrevious studies have reported that after laparoscopic cystectomy of ovarial endometrioma, the ovarian response to gonadotropin (Gn) significantly decreased. However, for patients with diminished ovarian reserve (DOR) after ovarian surgery, how to choose the most appropriate controlled ovarian hyperstimulation protocol has not been concluded. Compared with the traditional agonist regimen, the gonadotropin (Gn)-releasing hormone (GnRH) antagonist, microstimulation, and progestin-primed ovarian stimulation (PPOS) protocols are simple to operate and have a shorter cycle, which are often used in patients with DOR. So the purpose of our study is to compare the assisted reproductive outcomes of these three controlled ovarian hyperstimulation protocols in patients with DOR following laparoscopic cystectomy of ovarial endometrioma.MethodsIn this retrospective cohort study, 89 patients with DOR who had undergone in vitro fertilisation/intracytoplasmic sperm injection at the Department of Reproductive Medicine at the Third Affiliated Hospital of Zhengzhou University from 1 to 2018 to 31 December 2020 were included. According to the controlled ovarian hyperstimulation protocols employed, the patients were divided into GnRH antagonist (38 patients), PPOS (27 patients), and microstimulation (24 patients) groups. The basic data and clinical outcomes of the three groups were compared. The main outcome measure was the cumulative live birth rate.ResultsNo significant differences in the age of the female patients and their spouses and female patients’ body mass index and basal endocrine levels (follicle-stimulating hormone and oestradiol) were noted among the three groups (P > 0.05). The GnRH antagonist group had higher antral follicle counts, greater endometrial thickness on the human chorionic Gn injection day, greater number of oocytes retrieved, and higher two pronuclear embryo counts than did the other two groups. However, the starting dosage of Gn was lower in the GnRH antagonist group than in the other two groups. The microstimulation group had a significantly higher oocyte output rate and high-quality embryo rate than did the other two groups (P < 0.05). No significant differences in the total dosage of Gn, cumulative pregnancy rate, cumulative live birth rate, viable embryo rate, and blastocyst formation rate were observed among the three groups (P > 0.05).ConclusionIn conclusion, for patients aged under 40 years who experienced DOR after laparoscopic cystectomy of ovarial endometrioma, GnRH antagonist protocol and PPOS protocol can obtain better ovulation induction outcomes and cumulative live birth rate than microstimulation protocol, and are more suitable ovulation induction protocols.

Ultrastructure of coarse granules in the perivitelline space and association with ovulation induction protocols.

To evaluate the origin and ultrastructure of the coarse granules in the perivitelline space (PVS) of oocytes of a group of couples attending assisted reproduction treatment. The ultrastructure of five oocytes with coarse granulues in the PVS obtained from three patients were evaluated by transmission electron microscopy (TEM). The influence of the ovulation induction regimen on the formation of granules in the PVS of the oocytes of 214 couples and the developmental capacity of these oocytes presenting granules in the PVS was analyzed retrospectively. In TEM analysis, the microvilli structure was irregular, short, and loosely scattered through the oolemma in the oocytes presenting coarse granules in the PVS. Furthermore, dense lipid droplets were identified within the PVS and the surrounding cumulus cells. In retrospective analysis, the number of oocytes with coarse granules in the PVS was positively correlated with the duration of antagonist administration (r=0.23, p=0.013). Regardless of the type of granule, the presence of coarse or moderately coarse granules in the PVS was positively correlated with low-quality embryos on D3 (r=0.29, p=0.005) and the total number of arrested embryos up to D3 (r=0.33, p<0.001). Furthermore, the presence of coarse granules in the PVS severely exacerbated miscarriage rates. Our findings suggest that the presence of especially coarse granules in the PVS is correlated with the reduction of further embryonic developmental capacity in post-implantation stages of embryonic development, indicating a negative impact from aggressive ovulation induction protocols on developing oocytes.

Evaluation of factors predicting pregnancy by comparing successful IVF cycles with previous failed ones of the same patients in the same year

Aim: In this study, we aimed to examine the factors predicting pregnancy by comparing successful in vitro fertilization/ intracytoplasmic sperm injection (IVF)/(ICSI) fresh cycles with previous failed ones of the same patients in the same year. Materials and Methods: The study consisted of two groups, failed (n:283) and successful IVF fresh cycles (n:283) that applied one after another within the same year, thusly each woman acted under her own control. IVF treatment indications, antral follicle count, ovulation induction protocol type, initial and total gonadotropin dose, progesterone, and estradiol (E2) levels on the trigger day, the number of oocytes retrieved and mature oocytes, number of Grade 1, Grade 2, Grade 3 embryo, day of embryo transfer (ET), endometrial thickness on trigger and oocyte pick-up (OPU) day, embryo-fundus distance and beta-human chorionic gonadotropin (B-hCG) levels on the 10th day after the ET were measured. The same luteal phase support was administered in both groups. Results: Totally 566 cycles and 283 women were included in the study. There was a significant difference in luteinizing hormone (LH) levels on OPU day and number of grade 1 ET between the two groups, LH levels on OPU day and number of grade 1 ET were higher in successful IVF fresh cycles group (p&lt;0.05). Conclusion: Low serum LH levels on OPU day was associated with decreased pregnancy results. Increased IVF success was observed in grade 1 ET cycles.

Ovarian Response and Fertility after Short-Term Progestagen/eCG Treatments Are Compromised in Nulliparous Sheep during Non-Breeding Season.

The objective of this investigation was to determine the ovarian response, fertility, and prolificacy of nulliparous sheep when compared to multiparous sheep after a short-term (7 days) CIDR/eCG treatment which was administered during the non-breeding season. All the multiparous sheep, whereas only 54% of the nulliparous ewes, showed signs of estrus. However, 81.8% of the multiparous sheep and 100% of the nulliparous ewes ovulated. Fertility was also low after short-term progesterone treatments during the anestrous season in maiden sheep (30.8 vs. 72.7% in multiparous ewes). Such results indicate significant differences in the response to CIDR/eCG protocols for induction and synchronization of estrus and ovulation between nulliparous and multiparous sheep during the non-breeding season.

Association of anti-mullerian hormone and free androgen index level on response to clomiphene citrate in PCOS infertile women

BackgroundPolycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Clomiphene citrate, insulin-sensitizing drugs, aromatase inhibitors, gonadotropins, or laparoscopic ovarian drilling are various methods used for ovulation induction in women with PCOS. PCOS women with high levels of anti-mullerian hormone (AMH) and free androgen index (FAI) do not respond well to ovulation induction. This prospective observational study explores the relationship between FAI and AMH levels on ovarian response to clomiphene citrate in infertile women with PCOS. MethodsThis prospective observational study included 40 infertile with PCOS who underwent ovulation induction with clomiphene citrate with dose ranging from 50 to 150 ​mg. Participants were classified into four phenotypes by NIH(National Institute of Health) consensus panel criteria. The clinical and endocrine parameters of participants who were sensitive to clomiphene were compared to those who were resistant. ResultsThe most common phenotype was A, with all three features of PCOS: hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. There was no significant difference in clinical and endocrine parameters among the different phenotypes of PCOS except AMH and FAI values. The mean FAI was 9.39 ​± ​1.11 and AMH 7.26 ​± ​0.48 (ng/ml) in clomiphene resistant and 5.31 ​± ​1.93 and 3.69 ​± ​1.84 (ng/ml) respectively in clomiphene-sensitive women. Women with FAI > 7.5 and AMH >7 ​ng/ml might be resistant to clomiphene. ConclusionFAI and AMH values were significantly higher in women resistant to clomiphene induction. AMH and FAI may help women with PCOS to tailor their ovulation induction protocol.

AN OBSERVATIONAL ANALYSIS OF CLINICAL PROFILE ASSOCIATED WITH OVULATION INDUCTION USING LETROZOLE AMONG INFERTILE WOMEN WITH POLYCYSTIC OVARIAN SYNDROME

Background- Polycystic ovary syndrome (PCOS) is major endocrine and metabolic disease in reproductive women. As per latest procedures, letrozole should be taken as the rst-line pharmacological treatment for infertile women with PCOS. This study was planned to study the role of clinical prole in ovulation induction after letrozole therapy among infertile women with poly- cystic ovarian syndrome. This was a prospective analytical observational study carried out at the IVF centre, SMS Medical College,Methods- Jaipur. The present study enrolled 100 patients attending the IVF centre for fertility treatment who were diagnosed with PCOS as per Rotterdam criteria. Anthropometric measurements like Body mass index (BMI calculated as weight in kilograms divided by square of height in meters) and waist circumference (the smallest circumference at the level of umbilicus) was taken. A comprehensive physical examination of all patients was done to note signs of clinical hyperandrogenism like acne, alopecia, and hirsutism. Treatment response was dened as ovulation in response to letrozole in doses from 2.5 mg to 7.5 mg. In this study, women from 20 to 25 years of age with shorter duration of infertility, lower BMI,Results- lower waist circumference, absence of hirsutism, or mild hirsutism on clinical examination showed better response to Letrozole. Conclusion- Letrozole can be considered a suitable ovulation induction agent in infertile PCOS patients with lower BMI, lower waist circumference, and absence of hirsutism. A predictive ovulation score can be developed from basic clinical parameters. Identication of various factors affecting response to letrozole may help the clinician to individualize ovulation induction protocols in PCOS women.

P-677 Increasing the efficacy of FSH with a potentiating monoclonal antibody

Abstract Study question Can we potentiate FSH activity with antibodies to improve ovarian stimulation? Summary answer IGYXOS developed a potentiating monoclonal antibody that improves FSH potency and efficacy in vitro and in vivo as demonstrated in different animal models. What is known already FSH plays a key role in reproduction. For a controlled ovarian stimulation in IVF cycles, FSH-containing preparations are injected to patients in order to obtain mature and fertilizable oocytes. However, the efficacy of these treatments is frequently limited and sometimes several attempts are needed before reaching a pregnancy and a live birth. It was previously demonstrated that breeding animals treated with gonadotropins could develop anti-gonadotropin antibodies that enhance their bioactivity instead of inhibiting it. These females had a high kidding rate and sometimes were hyperprolific. Study design, size, duration IGYXOS developed a monoclonal antibody (mAb) directed against human FSH. The mAb CF12 was selected based on its ability to increase FSH activity in vitro and in vivo in female rat. Its potentiating activity was tested on different human FSH preparations. The potentiating effect of CF12 was further investigated in ewe treated with mAb alone or FSH alone. Participants/materials, setting, methods CF12 was tested in vitro on HEK 293 cells expressing the human FSH receptor and a cell reporter system for cAMP. In vivo, the mAb was tested according to the Steelman and Pohley protocol on different human FSH preparations. Its potentiating effect was also investigated in an ovulation induction protocol on mature ewes. Main results and the role of chance In HEK 293 cells expressing the human FSH receptor, CF12 combined to FSH improved both the potency (EC50) and the efficacy (Emax) of FSH by increasing the cyclic AMP production at all tested FSH concentrations. The potentiating activity was confirmed in immature female rats treated with hCG+FSH alone or combined to mAb, twice a day, during 3 days. The animals were sacrificed the fourth day of treatment and the weight of the ovaries was compared. Ovaries weight was significantly increased in the group treated with hCG/FSH+CF12 compared to hCG/FSH only. To further analyze the effect of CF12 on ovulation induction, it was investigated in ewe as a breeding animal model. Animals were first synchronized with a progestagen and then treated either with FSH alone or with CF12 alone. The number of ovulations was investigated by endoscopy by counting corpora lutea and the progesterone secretion was measured over the luteal cycle. All females treated with CF12 ovulated (100%) by contrast 40% ovulated with FSH treatment. The ovulation rate was 1.8 fold higher in group treated with CF12 compared to FSH group. Moreover, progesterone secretion during luteal phase was increased in animals treated with CF12 suggesting a better quality of corpora lutea. Limitations, reasons for caution After several proofs of concept obtained in different animal models, the compound is currently in the humanization phase before starting the CMC process and then preclinical studies. Wider implications of the findings The potentiating antibody CF12 is a new concept. It represents an interesting strategy in reproductive health, particularly to improve the IVF outcome. CF12 is currently developed for human application by our company and could be a game changer in the field of ovarian stimulation by enhancing the efficacy of FSH. Trial registration number not applicable

P-106 Total motile sperm count and oral ovulation induction protocols are not predictors of success in donor insemination cycles: Results from a large retrospective cohort study

Abstract Study question to investigate the effect of total motile sperm (TMS) count, and ovulation induction on clinical pregnancy rate in artificial insemination with donor (AID) cycles. Summary answer TMS count is not a predictor of sucess, and natural cycles are as effective as oral ovulation induction in donor inseminations What is known already There are inconsistent results regarding the effect of sperm parameters on success rates of artificial insemination with donor (AID). Besides, the use of gonadotropin stimulation for ovulation induction in this category of patients is questionable, and its effectiveness over natural cycles is not yet confirmed in the literature. Study design, size, duration Patients who underwent AID cycles at the university-affiliated fertility center-OVO clinic in Montreal, Canada between 2011 and 2015 were retrospectively selected. A total of 4333 AID cycles were performed on 1179 patients, resulting in 744 pregnancies. Participants/materials, setting, methods Cycles were divided into 8 groups based on TMS count: &amp;lt;0.5, [0.5-1[, [1-5[, [5-10[, [10-20[, [20-40[, [40-80[, and ≥80. A TMS of 10 to 20 million was selected as a reference level. Ovulation induction was divided into oral stimulation, combined oral and gonadotropin stimulation and gonadotropin-only stimulation, and compared to natural cycles. Regression analysis and a predictive model of clinical pregnancy in AID cycles were generated from patient demographic and cycle characteristics. Main results and the role of chance There was no significant difference in positive β-hCG result, clinical pregnancy, multiple pregnancy and miscarriage rates when comparing all ranges of TMS count to a reference of 10 to 20 million. When dividing patients based on the protocol for ovulation induction, clinical pregnancy rate was significantly higher in the gonadotropin-only stimulation group (OR 4.116,[1.379,12.287]) but not in other types of stimulation, as compared to natural cycles. hCG triggering resulted in a similar clinical pregnancy and miscarriage rates, but a higher multiple pregnancy rate when compared to urinary LH testing (7.7% versus 1.3%, p = 0.045). A multivariate logistic regression analysis for predictors of clinical pregnancy accounting for relevant demographic and cycle characteristics was conducted. No significant difference was noted in different ranges of TMS and the groups of ovulation induction. In this model, age was found to be a significant predictor. In particular, with every one-year increase in age, the odds of clinical pregnancy decreases by 6.4% (Adjusted OR 0.936; 95%CI [0.914, 0.958]). Limitations, reasons for caution In our study, cycles with TMS count below 1 million are limited. Thus, results should be viewed with caution in this group, without cycle cancellation, since clinical pregnancy can be achieved. Moreover, our results cannot be generalized on infertile couples given the characteristics of our population of interest. Wider implications of the findings Minimal or maximal cut-off values for TMS in AID cycles should not be used as indicators for cycle cancellation. Natural cycles are as successful as oral ovulation induction. hCG trigger, unless indicated, should not be used as it is associated with higher risk of multiple pregnancy without increasing clinical pregnancy. Trial registration number not applicable

Immunoregulatory Therapy Improves Reproductive Outcomes in Elevated Th1/Th2 Women with Embryo Transfer Failure.

Objective Immunological disturbance is one of the crucial factors of implantation failure. Limited data exists evaluating immunoregulatory therapy in patients with implantation failures. Methods This is a retrospective cohort study on patients who had failed embryo transfer cycle and had elevated Th1/Th2 cytokine ratios between 1/2019 and 3/2020. Patients were assigned into two groups based on whether they received immunoregulatory treatment during a frozen transfer cycle. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy, implantation rate, and neonatal outcomes. Results Of 71 patients enrolled, 41 patients received immunoregulatory therapy and 30 patients did not. Compared to untreated patients, rate of live birth was significantly elevated in the treated group (41.5% vs. 16.7%, P = 0.026). Rate of biochemical pregnancy, implantation, clinical pregnancy, and ongoing pregnancy between two groups were 56.1% vs. 40% (P = 0.18), 36.5% vs. 23.9% (P = 0.15), 51.2% vs. 30% (P = 0.074), and 41.5% vs. 16.7% (P = 0.03), respectively. Although there was no statistical significance, women receiving treatment also had a tendency of lower frequency of pregnancy loss (19.0% vs. 44.4%, P = 0.20). No adverse events were found between newborns of the two groups. Immunoregulatory therapy, age, infertility type, ovulation induction protocol, number of oocytes retrieved, artificial cycle embryo transfer, and cleavage transfer were associated with live birth in univariate analysis (all P < 0.05). Only immunoregulatory therapy was associated with live birth after adjustment of confounders (OR = 5.02, 95% CI: 1.02-24.8, P = 0.048). Conclusions Immunoregulatory therapy improves reproductive outcomes in elevated Th1/Th2 cytokine ratio women with embryo transfer failure.