Two prostanglandins (luprostiol, LUP, and dinoprost, DIN) and two ovulation-inducing agents (human Chorionic Gonadotropin, hCG, and deslorelin, DES) were evaluated for luteolysis and estrus induction, and for ovulation induction, respectively, in embryo donor jennies. Twenty-six fertile Andalusian jennies were used. In Experiment 1, jennies (n = 112 cycles) were randomly treated with either LUP or DIN after embryo flushing. In Experiment 2, donors (n = 84 cycles) were randomly treated with either hCG or DES to induce ovulation. No differences were found between prostaglandins for all variables studied (prostaglandin–ovulation interval (POI), interovulatory interval (IOI), embryo recovery rate (ERR), positive flushing rate (PFR) and embryo grade (EG)). The ovulation rate was similar for hCG and DES (60.9% vs. 78.7%). However, the interval to ovulation (ITO) was affected (62.61 ± 7.20 vs. 48.79 ± 2.69 h). None of the other variables studied (ERR, PFR and EG) were affected (p > 0.05), except for embryo quality (p = 0.009). In short, both prostaglandins evaluated are adequate to induce luteolysis and estrus. Both ovulation-inducing agents hastened ovulation, but DES seems to be more effective than hCG. Follicular diameter affected the interval from treatment to ovulation, and high uterine edema was related to low embryo quality.
What frozen-thawed embryo transfer (FET) protocol is associated with the highest live birth rate (LBR)? Summary answer: Natural cycle FET (NC-FET), with or without hCG triggering are associated with higher LBR and clinical pregnancy rate (CPR) compared to artificial HRT-FET cycles.
What is known already
FET cycles (as opposed to fresh ET) are now the most frequently performed treatment in ART. There are many reasons for this including better laboratory cryopreservation techniques, increased single ET cycles, freeze-all cycles to reduce OHSS, as well as PGT-A and personalized ET. Nevertheless, there is no clear consensus on the most effective protocol.
Study design, size, duration
Retrospective cohort study with FET of cleavage (n = 220) and blastocyst (n = 3258) embryos thawed 2013–2018 in a single academic center. FET protocols were NC-FET (n = 182), artificial HRT-FET (n = 3159) and modified NC (mNC) with hCG triggering (n = 137). Other cycles (gonadotrophin or GnRH agonist) and women with uterine anomalies were excluded. Primary outcome was LBR. Secondary outcomes were CPR, visits per cycle and endometrial thickness. Adjustment was made for potential known confounders.
Participants/materials, setting, methods
In NC-FET, no medication was given and ET timing was by serum LH surge. In mNC-FET, hCG was given when the lead follicle reached 18mm rather than awaiting the LH surge. In artificial HRT-FET, estradiol valerate was given and once endometrial thickness reached 8mm, progesterone was added and ET was planned. Adjustment for female age at oocyte retrieval, embryo stage, embryo grade, year of freezing, year of thawing, infertility cause and endometrial thickness was performed.
Main results and the role of chance
There were no significant differences between the groups with regard to female age at oocyte retrieval, embryo stage, embryo grade, embryo number, cycle number and endometrial thickness. As expected, more women with irregular cycles were included in the artificial HRT-FET compared to NC-FET (16.1% vs. 8.2%, p = 0.003) and mNC-FET (16.1% vs. 4.1%, p < 0.0001). There were more visits per cycle in NC-FET and mNC-FET compared to artificial HRT_FET (p < 0.0001). LBR was higher in the mNC-FET (38.0%) and NC-FET (31.9%) compared to artificial HRT_FET (20.2%) (p = 0.0001 and p = 0.0003 respectively). CPR was higher in mNC-FET compared to artificial HRT-FET (45.3% vs. 32.3%, p = 0.0002), and in NC-FET compared to artificial HRT-FET (44.5% vs. 32.3%, p = 0.0009). There was no significant difference in LBR or CPR between NC-FET and mNC-FET. Sub-analysis of the first FET showed similar results. Biochemical pregnancy loss and miscarriage rates were similar in all groups. The higher LBR with NC-FET and mNC-FET remained significant even after adjusting for potential confounders, (aOR 2.42, 95%CI: 1.53–3.66, p < 0.0001).
Limitations, reasons for caution
The interpretation of the findings of this study is limited by the retrospective nature of the analysis and the potential for unmeasured confounding variables.
Wider implications of the findings: Although artificial HRT FET cycles are more common, convenient and practical for clinicians, with less visits per cycle, its use must be cautiously reconsidered in light of the potential negative effect on LBR when compared with natural cycle FET.
Trial registration number
Melatonin has been documented to alleviate compromised pregnancies and enhance livestock performance traits. The objective of this study was to determine the effect of melatonin supplementation on milking traits in beef cattle dams and subsequent influence on calf performance. Cows (n = 60) were blocked based on embryo transfer donor and sire, potential calf breed and embryo grade. At d190, 220 and 250 of gestation, dams were administered either 2 subdermal ear melatonin implants (preMEL) or no implants (preCON). After parturition, birth weights were recorded and calves randomly received either melatonin implants (posMEL) or none (posCON) on approximately d 0, 30, and 60. At approximately d 60 of lactation, a subset of dams (n = 32) were selected based on age, weight and calf sex for milk collection and analysis. At weaning, calf weight and morphometric data were collected and adjusted according to weaning age. Prenatal melatonin administration did not change calf birth weight (P = 0.956). Milk yield tended to decrease in the preMEL group (P = 0.054) at 2.368 kg ± 0.11 compared to preCON at 2.054 kg ± 0.11. Milk fat percent tended to decrease (P = 0.07) in preMEL at 3.25 ± 0.19 versus preCON at 3.92 ± 0.19. There were no differences in prenatal treatment in respect to milk protein, lactose, solid non-fats, somatic cell count, and urea nitrogen (P > 0.16). At weaning, calf head circumference decreased (P < 0.031) in the preMEL group at 77.92cm ± 0.42 versus preCON at 79.31cm ± 0.45. Otherwise, there were no prenatal or postnatal treatment differences in respect to weaning weight, crown-rump length, hip height and head length (P > 0.12). Previous studies show crown-to-rump length and ponderal index differences. Our lack of differences might be attributed to geographical locations that impact day length or endogenous melatonin status.
The main purpose of this study was to investigate the effect of mean blastomere diameter (MBD) on pregnancy rates in in vitro fertilization (IVF) cases undergoing the long agonist cycle protocol. A total of 84 cases were evaluated within the scope of this observational prospective study. All cases were normoresponders, under 35 years old, with the long agonist protocol applied and single embryo (grade I or II) transfer performed. On the third day after ICSI, each embryo selected for transfer was subjected to measurement of the mean blastomere diameter (MBD) at ×25 magnification.
The mean female age was 30.14 ± 3.32 years, and the total clinical pregnancy rate was 33.3%. In the group that got pregnant, MBD was found to be statistically significantly higher than in the nonpregnant group. In terms of predicting clinical pregnancy, when the MBD value of 49.73 μm was accepted as the best cutoff value, the sensitivity was calculated as 75% and specificity as 53.6%. Clinical pregnancy rate was 18.9% in cases below this value, whereas clinical pregnancy rate was 44.7% in cases with this value and above. In other words, when the MBD value rose above 49.73 μm from a value below 49.73 μm, the clinical pregnancy rate increased by an average of 2.3 times.
With MBD measurement, it is possible to select the embryo with the best implantation capability in microinjection cycles with the long luteal agonist protocol.
Aim and objectives: The primary aim was to measure the sperm DNA damage and to study the magnitude of sperm DNA damage. Secondary objective was to study the effect of sperm DNA fragmentation on Day 5 Blastocyst expansion (graded 1-5). Results: There is an increase in sperm DNA fragmentation with an increase in age. Increased sperm DNA fragmentation is also associated with abnormal motility and morphology in semen samples. However, there is no reduction in expansion or grade of blastocyst. Conclusion: Sperm DNA fragmentation testing is a useful investigation in unexplained infertility. However, Sperm DNA fragmentation has no significant association with Day 5 embryo grade in ICSI cycles. Thesis work of Fellowship in Reproductive Medicine student: Dr. Ramya Harish