Impact of Living in Different Altitudes on Intracytoplasmic Sperm Injection (ICSI) Outcomes for Infertile Couples in Southwestern Region of Saudi Arabia, a Retrospective Study

Objective: The aim of this study was to determine the effect of different altitudes in the Southwestern region of Saudi Arabia on ICSI outcomes, fertilization rate, embryo quality, pregnancy rate, and miscarriage rates for infertile couples. Materials and Methods: This is a retrospective study on 551 infertile couples carried out in the Assisted Reproductive Technology unit at the Maternity and Childern Hospital in Abha, Saudi Arabia between 2018 and 2019 to compare ICSI outcomes in different altitudes. Low altitude (205 patients), mild altitude (86 patients) and high altitude (260 patients). Main result measurements: fertilization rates, embryo quality, clinical pregnancy and miscarriage rates at different altitudes. Results: The data showed that there were no significant differences (P>0.67) in fertilization rates and the number of good-quality embryos between different altitudes. Importantly, clinical pregnancy rates were similar between groups and there was no significant difference in the miscarriage rates between high, mild and low altitudes. Conclusions: This study demonstrates that there is now increased risk of miscarriage or low pregnancy rates with different altitudes in Southwestern region of Saudi Arabia. This suggests that altitude changes has no obvious risk on pregnancy rate and pregnancy outcome.

Can Time-Lapse Incubation and Monitoring Be Beneficial to Assisted Reproduction Technology Outcomes? A Randomized Controlled Trial Using Day 3 Double Embryo Transfer

Objective: To determine if the application of time-lapse incubation and monitoring can be beneficial to clinical outcomes in assisted reproductive technology.Methods: A total of 600 patients were equally randomized to three groups, namely, conventional embryo culture and standard morphological selection (CM group), time-lapse culture and standard morphological selection (TLM group), and time-lapse culture and morphokinetic selection (TLA group). Notably, 424 undergoing fresh autologous in vitro fertilization cycles were analyzed, 132 patients in the CM group, 158 in the TLM group, and 134 in the TLA group. Main outcomes included clinical outcomes, embryo development rates, and perinatal outcomes.Results: Clinical pregnancy rates in the time-lapse groups were significantly higher than in the CM group (CM 65.2% vs. TLM 77.2% vs. TLA 81.3%). Implantation rates and live birth rates were significantly higher for the TLA group (59.7 and 70.9%) compared with the CM group (47.7 and 56.1%) but not compared with the TLM group (55.4 and 67.1%). There was no statistical difference in miscarriage and ectopic pregnancy rates among the three groups. Overall, birth weight was significantly higher in the time-lapse groups (CM 2,731.7 ± 644.8 g vs. TLM 3,066.5 ± 595.4 g vs. TLA 2,967.4 ± 590.0 g). The birth height of newborns in the TLM group was significantly longer than that of the CM group and TLA group (CM 48.3± 4.4 cm vs. TLM 49.8± 2.3 cm vs. TLA 48.5± 2.7 cm).Conclusion: Time-lapse incubation and monitoring have a significant benefit on clinical pregnancy rates and on overall birth weights while morphokinetic analysis is not necessary.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02974517].

Effects of Vitrified Cryopreservation Duration on the IVF and Neonatal Outcomes

Objective: To evaluate the impact of cryopreservation storage duration on embryo viability, implantation competence, pregnancy outcome and neonatal outcomes.Design: Retrospective study.Setting: Center for Reproductive Medicine，The Third Affiliated Hospital of Guangzhou Medical University.Patient(s): In vitro fertilization patients who had vitrified cryopreserved embryos and following the first frozen embryo transfer cycles from January 2004 to August 2019. A total of 31143 patients met the inclusion criteria and were grouped according to the storage time (20926 patients in Group 1 with storage time <3 months, 6472 patients in Group 2 with storage time between 3 and 6 months, 2237 patients in Group 3 with storage time between 6 and 12 months and 746 in Group 4 with storage time between 12 and 24 months, 762 patients in Group 5 with storage time >24 months).Intervention(s): None.Main Outcome Measure(s): In the total FET cycles, the embryo survival rate was decreased significantly with the increase of cryopreservation time, and the highest rate was 98. 63 % in the 1-3 months group, and the lowest was 71.13% in the >=731 days group (P <0. 01). The HCG positive rate (57.85%) and clinical pregnancy rate (55. 26%) in the 1-3 months group were the highest (P<0. 01). The >=731 group had the lowest sex ratio of 0.96. There were no significant differences in neonatal birth weight, neonatal height and congenital anomalies among the groups (P>0. 05).Result(s): Length of storage time had a significant effect on post-thaw survival and outcomes for IVF cycles. Conclusion(s): With the prolongation of cryopreservation time, the embryonic survival rate and pregnancy rate were decreased significantly. Short-term cryopreservation (<=3 months) can obtain higher clinical pregnancy rate. Therefore, although long-term hryopreservation of the embryo has no effect on the health of the new baby, but hryopreserved embryos should be recovery as soon as possible if condition allows.

Does serum progesterone level impact the ongoing pregnancy rate in frozen embryo transfer under artificial preparation with vaginal progesterone? Study protocol for a randomized controlled trial

Background In previous retrospective studies, low serum progesterone level on the embryo transfer day is associated with lower clinical pregnancy and ongoing pregnancy rates. Whether adding progesterone in low serum progesterone patients can rescue the outcome, there is no sufficient evidence from randomized controlled studies. Methods This trial is a clinical randomized controlled study (high serum progesterone vs low serum progesterone 1:1, 1:1 randomization ratio of intervention vs the control group with low serum progesterone). The eligible hormone replacement therapy—frozen embryo transfer (HRT-FET) cycles, will be recruited and randomly assigned to two parallel groups when serum progesterone is < 7.24μg/l on the day of embryo transfer for D3. The intervention group will be extrally given intramuscular progesterone 40 mg per day from D3 to 8 weeks of gestation if clinical pregnancy. The primary outcome is the ongoing pregnancy (beyond 12 weeks of gestation) rate. Discussion The findings of this study will provide strong evidence for whether the progesterone addition from the D3 in low serum progesterone patients can improve the outcome in the HRT-FET cycle. Trial registration ClinicalTrials.govNCT04248309. Registered on January 28, 2020

Effect of Intrauterine Administration of Seminal Plasma for Patients with Recurrent Implantation Failure Before FET: Study Protocol for a Prospective Randomised Controlled Trial

Background: To assess the effect of intrauterine administration of seminal plasma for patients with recurrent implantation failure before frozen-thawed embryo transfer. Methods: Trial design: This is a parallel group, randomized (1:1 allocation ratio) controlled trial.Participants: All patients will be recruited from Chengdu Women’s and Children’s Central Hospital. Inclusion criteria: 1. Women after IVF/ICSI treatment in Chengdu Women’s and Children’s Central Hospital. 2.Infertile women with a history of recurrent implantation failure. 3.Infertile couples (both male and female) aged between 20 and 39 years;4. Couples who have at least 1 good quality embryos for transfer. 5. Males had negative in infectious disease test. 6. The males have semen. 7. Women who intend to undergo FET after IVF or ICSI or pre-implantation genetic testing for aneuploidy (PGT-A). 8. Competent and able to give informed consent. Intervention and comparator: Treatment group receiving intrauterine administration of seminal plasma before frozen-thawed embryo transfer. Main outcomes: Clinical pregnancy after frozen-thawed embryo transfer. Randomisation: Patients will be randomly allocated to either treatment or control group at 1:1 ratio. Random numbers will be generated by using software SPSS 25.0 performed by an independent statistician from Chengdu Women’s and Children’s Central Hospital. Blinding (masking): Only the data analyst will be blinded to group assignment. Numbers to be randomised (sample size): To account for a 10% dropout rate, we will recruit 174 patients (87 in each group). Trial status: The date of approval is 31rd May 2021, version 2.0. Recruitment started on 1rd June and is expected to end in July 2022. Discussion: Intrauterine administration of seminal plasma before frozen-thawed embryo transfer of patients with recurrent implantation failure may improve clinical pregnancy rate, it has great Page 2 of 14 significance for assisted reproduction. Trial registration: The study protocol has been approved by the ethics committees at Chengdu Women’s and Children’s Central Hospital. The trial was registered at the Chinese Clinical Trial Registry ChiCTR2100046803. Registered on 28 May 2021.

Analysis of Biochemical and Clinical Pregnancy Loss Between Frozen-Thawed Embryo Transfer of Blastocysts and Day 3 Cleavage Embryos in Young Women: A Comprehensive Comparison

BackgroundTo determine whether the embryo developmental stage affects biochemical or clinical pregnancy loss in young women undergoing frozen-thawed embryo transfer (FET) and to investigate the underlying mechanism.MethodsThis was a retrospective study including a total of 18,34 β-HCG (human chorionic gonadotropin)-positive FET cycles. According to the morphological appearance (MA) of transferred blastocysts, FET cycles with blastocysts were divided into two groups: Group A: morphologically good (MG) blastocysts only, and Group B: at least one morphologically non-good (MNG) blastocyst. FET cycles with day 3 cleavage embryos were assigned as Group C. Biochemical and clinical pregnancy loss were the main outcome measures.Result(s)We predicted 78% in vivo-formed MG and 53.9% in vivo-formed day 5 blastocysts in Group C. (a) Including cases in Group A and Group B for binary logistic regression, we showed that Group B and day 6 blastocysts had significantly higher rates of BPL and CPL than Group A and day 5 blastocysts, respectively. (b) Including cases in Group A, Group B, and Group C for binary logistic regression, we showed that Group C had a significantly higher rate of BPL than Group A and day 5 blastocysts and a similar rate of BPL as Group B and day 6 blastocysts. Group C had a higher rate of CPL than Group A (p=0.071) and day 5 blastocysts (p=0.039), and a lower rate of CPL than Group B (p=0.199) and day 6 blastocysts (p=0.234).Conclusion(s)(1) MA and days of usable blastocysts could serve as independent factors affecting the occurrence of BPL and CPL. (2) Transfer of day 3 cleavage embryos may produce “unusable blastocysts” in vivo, which significantly increased the rate of BPL. (3) The rate of CPL resulting from the transfer of day 3 embryos may depend on the rate of in vivo-formed MG or day 5 blastocysts. Our study indicated that the difference in the BPL or CPL between transfer of blastocysts and day 3 cleavage embryos may largely depend on the quality of embryos transferred.

EMBRYO GLUE AND CLINICAL PREGNANCY RATES IN ICSI EMBRYO TRANSFER CYCLES: A PROSPECTIVE STUDY

Purpose: One of the reasons for failed implantation after transferring good quality embryos in an intracytoplasmic sperm injection cycle is the failure of creation a viscid layer between the embryo and the endometrium. Many modifications have been made in embryo transfer medium to improve implantation and increase pregnancy rates such as adding albumin as a source of energy and adding hyaluronic acid in high concentrations such as in Embryo Glue medium: a human embryo transfer medium. To investigate whether the use of Embryo Glue had any effect on clinical pregnancy rates in intracytoplasmic sperm injection-fresh embryo transfer cycles. Methods: A prospective study included one hundred and twenty-eight infertile Iraqi women who were selected and subjected to a stimulation protocol in an intracytoplasmic sperm injection-fresh embryo transfer cycle. All patients were considered to be eligible for embryo transfer (no visible causes could prevent implantation) and only good quality embryos were transferred to them. Those women were divided randomly into two groups according to type of embryo transfer medium: group A: Embryo Glue medium. group B: Conventional medium. Then group A was subdivided according to age into: AI (34 women with age < 35 years and represented 50.7%) AII (33 women with age ≥ 35 years and represented 49.3%) While group B was subdivided into: BI (41women with age < 35 years and represented 67.3%) BII (20 women with age ≥ 35 years and represented 32.7%). Results: Although there was no significant difference between all groups in causes of infertility, the pregnancy rate was significantly higher in subgroup AII (18 pregnant from 33 women) while only 5 patients became pregnant from 20 patients in subgroup BII. In all women no more than four good quality embryos were transferred, and when total number of transferred embryos was significantly more in group B than group A (P=0.013), the significant increase in pregnancy rates was only observed in subgroup AII (P=0.048). Even though a highly significant difference in number of repeated implantation failure was in group A than group B (P=0.027), the pregnancy rates were significantly higher in group A (P=0.038). Conclusion: This study concluded that using Embryo Glue has a beneficial effect on old women and increase pregnancy rates, also it has a positive effect on pregnancy rates in repeated implantation failure and increases pregnancy rates even if the women is old.

Combined treatment of prednisone and hydroxychloroquine may improve outcomes of frozen embryo transfer in antinuclear antibody-positive patients undergoing IVF/ICSI treatment

Background The influence of anti-nuclear antibody (ANA) on induced ovulation was controversial, and the effect of prednisone plus hydroxychloroquine (HCQ) treatment on frozen embryo transfer outcomes of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for ANA-positive women was unclear. Methods Fifty ANA-positive women and one-hundred ANA-negative women matched for age and anti-Mullerian hormone (AMH) were included from a Reproductive Medical Central of a University Hospital. Sixty-one oocytes pick-up (OPU) cycles in ANA+ group and one-hundred OPU cycles in ANA− group were compared; 30 frozen embryo transfer cycles without treatment and 66 with prednisone plus HCQ treatment among ANA-positive women were compared. Results There was no statistical difference in number of retrieved oocytes (13.66 ± 7.71 vs 13.72 ± 7.23, p = .445), available embryos (5.23 ± 3.37 vs 5.47 ± 3.26, p = .347), high-quality embryos (3.64 ± 3.25 vs 3.70 ± 3.52, p = .832), and proportion of high-quality embryos (26.5% vs. 26.7%, p = .940). Biochemical pregnancy rate (33.3% vs. 68.2%, p < .05), clinical pregnancy rate (20.0% vs. 50.1%, p < .05), and implantation rate (5.6% vs. 31.8%, p < .05) were lower, and pregnancy loss rate (83.3% vs. 23.1%, p < .05) was higher in patients with treatment than no treatment. Conclusion The influence of ANA on number of retrieved oocytes, available embryos, high-quality embryos, and proration of high-quality embryos was not found. The treatment of prednisone plus HCQ may improve implantation rate, biochemical pregnancy rate, and clinical pregnancy rate, and reduce pregnancy loss rate in frozen embryo transfer outcomes for ANA-positive women.

Uterine Factors Modify the Association Between Embryo Transfer Depth and Clinical Pregnancy: A Retrospective Study in 7849 Fresh Transfer In Vitro Fertilization Cycles

The embryo position is supposed to affect implantation following embryo transfer. However, embryo dislodging caused by uterine contraction may occurred after transfer. The retrospective study was to investigated whether the factors associated with uterine contractility, such as endometrial thickness and progesterone elevation, affect the association between embryo position and implantation. A total of 7849 fresh transfer cycles on conventional stimulation in a single IVF centre during the period 2013–2015 was reviewed. Patients were categorized according to quartiles of embryo-fundus distance (≤9, 9.1-11, 11.1-14, ≥1.4 mm, respectively). Adjusted for confounding factors, the odds ratio (OR) (95%CI) for clinical pregnancy was 0.90 (0.79-1.02), 0.86 (0.74-0.99) and 0.70 (0.60-0.82) respectively in quartiles 2 through 4, comparing with quartile 1. However, ORs were significantly increased when endometrial thickness was < 8 mm. The ORs comparing quartiles 2 through 4 with quartile 1 increased 1.96 (95%: 1.33-2.90), 1.20 (95%: 0.78-1.87) and 1.98 (95%: 1.20-3.26) fold respectively in cycles with an endometrial thickness < 8 mm than in cycles with a normal endometrial thickness (8-11 mm). Elevated progesterone on the day of hCG and blastocyst stage transfer reduced the ORs. Our data suggested an interaction between patient characteristics and embryo transfer techniques.