Comparison of the effects of two different trigger strategies - dual (hCG + Leuprolide) versus hCG trigger - in antagonist non-donor IVF: a randomized controlled trial.

OBJECTIVE: Conventionally, hCG is used as a 'faux' LH surge to bring final oocyte maturation due to structural similarity with LH. Although GnRH agonists induce a more physiological gonadotropin surge for follicular maturation, they have been associated with luteal phase deficiency. Our aim was to assess whether adding a gonadotropin-releasing hormone agonist (GnRHa) to hCG trigger improves oocyte maturation and the number of high-grade embryos in GnRH antagonist IVF cycles. METHODS: This was a single center, open-labelled, randomized controlled trial including 100 patients between 21-38 years (tubal factor, male factor, unexplained infertility, with normal ovarian reserve) undergoing IVF using the GnRH antagonist protocol. Patients were randomized to receive either the dual trigger (Leuprolide acetate 1mg + rhCG 250µg, n=50) or a single hCG trigger (rhCG 250µg, n=50). Analysis was done by ITT. Independent-t and chi-square tests were used in the comparisons of normally distributed quantitative variables and qualitative variables. RESULTS: With similar baseline characteristics, the number of MII oocytes (7.82 vs. 5.92, p=0.003) and day-3 grade-1 embryos (4.24 vs. 1.8, p<0.001) and consequently, number of embryos cryopreserved (2.68 vs. 0.94, p<0.001) were significantly higher in the dual trigger group. However, the fertilization (91.82% vs. 88.51%, p=0.184) and clinical pregnancy rates between the two groups (21% vs. 19.6%, p=0.770) were comparable. Serum LH levels 12 hours post trigger were high in the dual trigger group (46.23mIU/ml vs. 0.93mIU/ml, p<0.0001). CONCLUSIONS: This study found that the addition of GnRHa to hCG trigger leads to improved embryological outcomes and the possibility of cryopreserving surplus embryos, thereby increasing cumulative live births.

Using GnRH agonists in combination with hCG in antagonist ART cycles: A SCOPING Review of recent evidences.

Assisted Reproductive technology encompasses all techniques involving ovarian stimulation to produce high-quality oocytes and manipulation of both oocytes and sperm in vitro to produce embryos for the purpose of reproduction. The final maturation of oocytes induced by a "trigger" is a crucial step with the potential to affect in vitro fertilization outcomes. Human chorionic gonadotropin has traditionally been used as a substitute for luteinizing hormone to induce final oocyte maturation and meiosis. However, this practice may cause a potentially fatal iatrogenic complication known as ovarian hyperstimulation syndrome, which can cause significant morbidity and, in rare cases, death in otherwise healthy women. Thus, gonadotropin releasing hormone agonists have been promoted as a safer alternative for inducing oocyte maturation, albeit at the expense of luteal phase defect. Since then, various combinations of gonadotropin releasing hormone agonists and human chorionic gonadotropin have been tried. This scoping review evaluates these trigger combinations in various types of responders.

In vitro fertilization as an independent risk factor for perinatal complications: Single-center 10 years cohort study.

OBJECTIVES: Assisted Reproductive Technology (ART) has made great strides in the past forty-years, but no medical treatment comes without side effects. Despite several studies reporting high incidences of perinatal complications, the association is inconclusive. Also, the effect of racially and ethnically distinguished Asian population undergoing ART on perinatal outcomes is not well studied. Therefore, this study attempts to compare various perinatal outcome parameters in ART, and spontaneously conceived singleton pregnancies from a single high-volume tertiary care center. METHODS: This is a retrospective cohort study from a single tertiary infertility center, carried out from January 2011 to September 2020. The study included 1,125 IVF conceived babies (AB group) and 7,193 spontaneous conceived babies (SB group). The groups were compared using the Pearson Chi-square test and adjusted odds ratio, calculated using the multivariate analysis. RESULTS: Most of the perinatal complications, such as preterm birth (PTB), early preterm birth, low birth weight (LBW), extremely low birth weight, small for gestational age, large for gestational age babies, neonatal intensive care unit (NICU) admission, need for surfactant, meconium aspiration syndrome, neonatal seizures, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and patent ductus arteriosus was significantly increased in the AB group when compared to the SB group (p<0.05). In-vitro fertilization (IVF) independently increases the risk of LBW (aOR 2.530; 95% CI 2.194-2.917), PTB (aOR 4.004; 95% CI 3.496-4.587), NICU admission (aOR 2.003; 95% CI 1.610-2.492) and neonatal seizures (aOR 9.805; 95% CI 5.755-16.706).Conclusions: All ART-conceived pregnant patients should receive antenatal counselling regarding perinatal complications and should deliver at a tertiary care center with appropriate NICU support.

Serum progesterone on the day of human chorionic gonadotropin (hCG) trigger as a predictor of in-vitro fertilization (IVF) outcome - a retrospective analysis of seven years.

OBJECTIVE: To investigate the relationship between progesterone (P4) levels on the day of hCG trigger and IVF outcomes. METHODS: This is a retrospective analysis of IVF cycles from January-2013 to December-2019 from a single center. Women (21-39 years) submitted to IVF treatment for various infertility factors were included, while donor oocyte cycles and cancelled cycles were excluded from the study. The primary outcome measure was live birth rate. RESULTS: A total of 2149 cycles were analyzed. Of these, 223 (10.38%) were in the low P4 group (<0.5 ng/ml), 1163 (54.12%) in the normal P4 group (0.5-1.5 ng/ml), and 763 (35.50%) in the high P4 group (>1.5ng/ml). The groups were comparable with respect to age, factor of infertility and baseline AMH. The antagonist protocol was significantly more prescribed to the high P4 group (p<0.001). Live birth rates were 14.4%, 21.6%, and 21% (p<0.001), respectively, in three groups. Univariate analysis found that total cetrotide dose, total number of retrieved and fertilized oocytes, total number of embryos formed, transferred, and vitrified, and P4 on the day of hCG (p<0.001) were statistically significant after adjusting for age and BMI. In multivariate logistic regression after adjusting for age and BMI, only high P4 (aOR:0.60; p<0.001), total cetrotide dose (aOR: 0.82; p<0.001), and total utilizable embryos (aOR:1.11; p=0.029) were statistically significant. CONCLUSIONS: Having an elevated serum progesterone level on the day of hCG trigger was associated with lower pregnancy rates, but this is still not a robust marker to predict live births. More good quality evidence is needed.

Comparing maternal outcomes in spontaneous singleton pregnancies versus in vitro fertilization conception: Single-center 10-year cohort study.

OBJECTIVE: A successful assisted reproductive technique (ART) cycle is not flawless, and several studies have reported high incidences of maternal complications, but the association is inconclusive. In addition, the racial and ethnic effects of the Asian population undergoing ART on maternal outcomes is not well studied. This study attempts to compare various maternal outcome parameters ART and spontaneously conceived singleton pregnancies from a single high volume tertiary care centre. METHODS: A retrospective cohort study from a single tertiary infertility center was conducted from January 2011 to September 2020. The study included 1125 IVF conceived singletons (AP group) and 7193 spontaneous conceived singletons (SP group). The groups were compared using the Pearson Chi-square test and the adjusted odds ratio calculated using multivariate analysis. RESULTS: Maternal outcomes like gestational hypertension, pre-eclampsia, gestational diabetes (GDM), oligohydramnios, chorioamnionitis, operative, and instrumental delivery were significantly different in the two groups (p<0.05). The AP group had a significantly increased risk of GDM (aOR 1.093; 95% CI 1.076-1.110) and pregnancy-induced hypertension (PIH) (aOR 1.577; 95% CI 1.288-1.930) as compared to the SP group. IVF significantly increases the risk of abruption by 2 times (p=0.028), and independently increases the risk of caesarean section by 3.1-fold (p<0.001). But overall the IVF is the protective factor for oligohydramnios (p=0.024). CONCLUSIONS: ART increases the likelihood of pregnancy-related maternal complications, such as PIH, GDM, abruption, chorioamnionitis, and an increased rate of caesarean delivery. Thus, all patients undergoing ART procedures should receive pre-conceptional counselling regarding the associated obstetric risks and consider ART pregnancy as a high-risk pregnancy.

Endometritis - Diagnosis,Treatment and its impact on fertility - A Scoping Review.

Endometritis is defined as an infection or inflammation of the endometrium. Endometritis is of two types: acute and chronic. Acute endometritis is the symptomatic acute inflammation of the endometrium, which upon examination with a microscope shows micro-abscess and neutrophil invasion in the superficial endometrium. One of its most common manifestations is postpartum endometritis. Chronic endometritis is a silent disease usually diagnosed on the workup of secondary amenorrhoea and infertility. An important cause of chronic endometritis is tuberculosis, especially in developing nations. Chronic and acute endometritis have been associated with poor reproductive outcomes. Worse outcomes have been reported for individuals with chronic endometritis. This is a scoping review of endometritis and its impact on fertility.

Autologous platelet-rich plasma optimizes endometrial thickness and pregnancy outcomes in women with refractory thin endometrium of varied aetiology during fresh and frozen-thawed embryo transfer cycles.

OBJECTIVE: To evaluate whether platelet-rich plasma (PRP) optimizes endometrial thickness (EMT) and improves live birth rates (LBR) in women with refractory thin endometrium due to varied aetiology during fresh in vitro fertilization (IVF) and frozen-thawed embryo transfer (FET). METHODS: A prospective interventional study was conducted at the ART Centre of a tertiary care academic hospital. Twenty-two infertile women with refractory thin endometrium (<7mm) despite standard hormone replacement therapy were assessed. Twenty patients underwent 26 PRP cycles from December 2018 - June 2020 during fresh IVF-ET and FET. Primary endpoint was expansion of EMT and secondary outcomes were implantation rate (IR), clinical pregnancy rate (CPR) and LBR in fresh and FET cycles and aetiology wise. RESULTS: Mean EMT increased significantly following PRP administration (p<0.001) with average increase of 1.07mm and 0.83mm after first PRP (p<0.001) during fresh IVF and FET, respectively. CPR, IR and LBR showed no significant difference when compared during fresh vs. FET cycles (p>0.05). PRP led to significant increase in EMT in tuberculosis (TB), diminished ovarian reserve (DOR) and polycystic ovary syndrome (PCOS) (p<0.001). There was no significant difference in CPR, IR and LBR among three aetiological factors (p>0.05). Overall, clinical pregnancy and LBR reached up to 20% and 25%, respectively. No adverse reactions were reported. CONCLUSIONS: PRP enhances EMT significantly during fresh and FET cycles in thin endometrium associated with TB, PCOS and DOR, thus improving the CPR and LBR in these low prognosis patients.

Multivariate analysis of oocyte donor and recipient factors affecting cumulative live birth rate in oocyte donor IVF (OD-IVF) cycles.

OBJECTIVE: To study donor and recipient factors affecting cumulative live birth rate (CLBR) in oocyte donor IVF (OD- IVF) cycles. METHODS: The present retrospective study was conducted at the ART center of a tertiary care referral hospital after ethical approval, and included all OD-IVF cycles done between January 2014 - October 2019. Donor parameters included age, body mass index (BMI), ovarian reserve markers, serum estradiol (E2) on trigger day, and number of total/grade 1 oocytes; recipient parameters included age and BMI. The primary outcome was CLBR resulting from one complete donor-recipient (D-R) cycle through fresh/frozen embryo transfer. Secondary outcomes included number of total and grade 1 oocytes, fertilization rate, cleavage rate and clinical pregnancy rate (CPR). RESULTS: We analyzed 262 D-R cycles for donor characteristics and 260 cycles for CLBR. The mean age of the recipients was 35.20±4.05, and for donors it was 25.29±2.03 years. The CPR and CLBR per started cycle was 60% and 55.7%, respectively. Recipient BMI and grade 1 oocytes were found to be independent predictors of CLBR in multivariate analysis. As the number of grade 1 oocytes increased, the likelihood of live births increased by 10% (95% CI, 1.04 - 1.32, p=0.008). Recipient BMI ≥25kg/m2 reduced the chances of CLBR by 50% (95% CI, 0.27 - 0.81, p=0.007). CONCLUSIONS: Number of grade 1 oocytes and recipient BMI significantly affect CLBR in OD-IVF cycles. Recipients with BMI ≥25kg/m² may be advised to lose weight and improve CLBR likelihood.

Does basal luteinizing hormone help predict the fate of in vitro fertilization?

OBJECTIVE: Evaluate the role of baseline serum luteinizing hormone (LH) in predicting the success of in-vitro fertilization (IVF) in terms of clinical pregnancy and live birth rate. METHODS: Women who underwent IVF and/or intracytoplasmic sperm injection (ICSI), following either the agonist or the antagonist protocol, were retrospectively evaluated over a period of two years at the All India Institute of Medical Sciences, New Delhi. We investigated the correlation of serum LH levels in the follicular phase with pregnancy outcomes. A P-value lower than 0.05 was considered as statistically significant. RESULTS: The individuals (351) were divided into four groups based on LH and FSH baseline values, and the levels were correlated with clinical pregnancy and live births. The highest clinical pregnancy rate (25%) was achieved in women with low LH (< 2IU/l); whereas the miscarriage rate was almost similar in all the groups. The pregnancy rate was the lowest (16%) in women with high LH levels (> 8IU/L). Pregnancy rates were intermediate (20%) if LH was intermediate (2-8IU/L). However, none of the results had statistical significance. CONCLUSIONS: Early follicular serum LH levels before an IVF/ICSI treatment cycle did not have any clear relationship with clinical pregnancy or live birth rates.