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.

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.

Improving IUI success by performing modified slow-release insemination and a patient-centred approach in an insemination programme with partner semen: a prospective cohort study

Background: Pregnancy rates after in vitro fertilisation (IVF) treatment continue to improve, while intrauterine insemination (IUI) programmes show no such trend. There is a need to improve success rates with IUI to retain it as a viable option for couples who prefer avoiding IVF as a first line treatment. Objective: To investigate if a modified slow-release insemination (SRI) increases the clinical pregnancy rate (CPR) after intrauterine insemination (IUI) with partner semen. Materials and Methods: This was a prospective cohort study in a Belgian tertiary fertility centre. Between July 2011 and December 2018, we studied data from an ongoing prospective cohort study including 989 women undergoing 2565 IUI procedures for unexplained or mild/moderate male infertility. These data were analysed in order to study the importance of different covariates influencing IUI success. Generalised estimating equations (GEEs) were used for statistical analysis. Results of two periods (2011-2015, period 1 and 2016-2018, period 2) were examined and compared. From January 2016 (period 2) onwards, a standardised SRI procedure instead of bolus injection of sperm was applied. The primary outcome parameter was the difference in clinical pregnancy rate (CPR) per cycle between period 1 (bolus IUI) and period 2 (modified SRI). Secondary outcome results included all other parameters significantly influencing CPR after IUI. Results: Following the application of modified SRI the CPR increased significantly, from 9.03% (period 1) to 13.52% (period 2) (p = 0.0016). Other covariates significantly influencing CPR were partner’s age, smoking/non-smoking partner, BMI patient, ovarian stimulation protocol and Inseminating Motile Count (after semen processing). Conclusions: The intentional application of modified slow-release of processed semen appears to significantly increase CPRs after IUI with homologous semen. Future studies should investigate whether SRI, patient-centred measures, or a combination of both, are responsible for this improvement.

Effect of traditional Chinese medicine formula Guilu Xian on in vitro fertilization and embryo transfer outcome in older women with low prognosis: study protocol for a prospective, multicenter, randomized double-blind study

Introduction In recent years, the prevalence of infertility has significantly increased and has become a global reproductive health problem. The female ovarian reserves have been shown to decrease progressively with an increase in age. Besides, the rate of embryo implantation and clinical pregnancy also decreases. Traditional Chinese medicine has been widely applied in assisted reproductive technology. It is reported to have a significant influence on improving the quality of oocytes, improving endometrial receptivity, increasing clinical pregnancy rate, reducing pregnancy-related complications, etc. Therefore, this study will investigate the effect of Guilu Xian, a traditional Chinese medicine formula on IVF-ET outcome in older women with low prognosis. Methods and analysis This trial is a prospective, multicenter, randomized double-blind clinical trial. A total of 120 infertile patients with low prognosis and receiving IVF or ICSI in 3 public hospitals in China will be randomly divided into two parallel groups: Guilu Xian group (n = 60) and placebo group (n = 60). Patients in both groups will be treated with antagonist regimens to promote ovulation, and all the patients will be required to take the medication from the 2nd to 4th day of the menstrual cycle to the day of egg retrieval. A comparison of the total number of oocytes obtained, the fertilization rate, clinical pregnancy rate, embryo quality, embryo implantation rate, and early spontaneous abortion rate between the experimental group and the placebo group will be performed. Trial registration Chinese Clinical Trials Registry ChiCTR1900028255. Registered on 16 December 2019.

Exploration of the value of progesterone and progesterone/estradiol ratio on the hCG trigger day in predicting pregnancy outcomes of PCOS patients undergoing IVF/ICSI: a retrospective cohort study

Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder with the disorders of estrogen(E2) and progesterone(P) secretion. The purpose of this study was to evaluate the association between the progesterone level or progesterone/estradiol(P/E2) ratio on human chorionic gonadotropin (hCG) trigger day and the outcome of in vitro fertilization in PCOS patients and explore the value of progesterone and P/E2 ratio for predicting the clinical pregnancy. Methods The clinical data of 1254 PCOS patients who satisfied the inclusion criteria were retrospectively analyzed, including baseline characteristics such as age, body mass index, basal sex hormone levels, et al., as well as ovarian stimulation data and clinic outcome. Results The number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001) was greater in the high progesterone group (progesterone ≥ 0.92 ng/mL). In the high P/E2 group(P/E2 ratio ≥ 0.3), the number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001), as well as the rate of high-quality embryos (P = 0.040) were significantly decreased. In ultralong GnRH agonist protocol, the implantation rate(P < 0.001), hCG positive rate (P < 0.001), clinical pregnancy rate (P < 0.001) and live birth rate (P < 0.001) were all significantly higher than long GnRH agonist protocol and GnRH antagonist protocol. The clinical pregnancy rate of high progesterone group was significantly lower than that of low progesterone group in ultralong GnRH agonist (P = 0.008). The progesterone level could be used as an indicator to predict the positive clinical pregnancy (long GnRH agonist: P = 0.001; ultralong GnRH agonist: P < 0.001) except in cycles using GnRH antagonist (P = 0.169). In the ultralong GnRH agonist, the value of progesterone level in the prediction of clinical pregnancy was significantly higher than that of the P/E2 ratio (P = 0.021). Conclusions In PCOS patients, the progesterone level is associated with clinical pregnancy rate while P/E2 ratio is not. In subgroup analysis using three different COS protocols, a significant association between progesterone level and clinical pregnancy rate can be observed in the long GnRH agonist protocol and ultralong GnRH agonist protocol. The progesterone level is significantly better than the P/E2 ratio in predicting the pregnancy outcome of PCOS patients, especially in ultralong GnRH agonist cycles.

The effect of air bubble position on ART outcome in frozen-thawed blastocyst transfer

Background So far, only few literatures have studied the relationship between blastocyst transfer position and ART outcomes, and the conclusions are still controversial. Our study is to evaluate the effect of air bubble position on ART outcome and to find the optimal embryo transfer position in frozen-thawed blastocyst transfer. Methods This study included a retrospective cohort analysis of 399 frozen-thawed single blastocyst transfers ultrasound-guided performed between June 1, 2017 and November 30, 2020. All of the women scheduled for frozen-thawed single blastocyst transfers ultrasound-guided. The primary outcome is clinical pregnancy rate and the secondary outcome is live birth rate. Statistical analyses were conducted using One-way Anova, Kruscal Whallis H test, chi-square test and Smooth curve fitting. Results When BFD was less than 19 mm, there was no significant change in clinical pregnancy rate as BFD increased (OR = 0.95, 95% CI: 0.89 to 1.02, P = 0.1373); when BFD was more than 19 mm, the clinical pregnancy rate decreased by 16% for every 1 mm increase in BFD (OR = 0.84, 95% CI: 0.72 to 0.98, P = 0.0363). The effect of BFD on live birth rate were similar to that on clinical pregnancy rate, the inflection point was 19mm, when BFD was more than 19 mm, the live birth rate decreases by 58% for every 1 mm increase in BFD (OR = 0.42, 95% CI: 0.21 to 0.86, P = 0.0174) Conclusions The ideal pregnancy outcome can be achieved within 19mm from uterus fundus after single blastocyst transfer, The clinical pregnancy and live birth at a distance of more 19mm from the uterus fundus have a cliff-like downward trend.

Twice vitrification-warming procedures has no effect on frozen-thawed embryo transfer outcomes

Background To evaluate the frozen-thawed embryo transfer (FET) outcomes of repeated cryopreservation by vitrification of blastocysts derived from vitrified-warmed day3 embryos in patients who experienced implantation failure previously. Methods We retrospect the files of patients who underwent single frozen-thawed blastocyst transfer cycles in our reproductive medical center from January 2013 to December 2019. 127 patients transfer of vitrified-warmed blastocysts derived from vitrified-warmed day3 embryos were defined as twice-cryopreserved group. 1567 patients who transfer blastocysts that had experienced once vitrified-warmed were used as once-cryopreserved group. None of them was pregnant at the previous FET. The outcomes were compared between two groups after a 1:1 propensity score matching (PSM). Results The clinical pregnancy rate was 52.76%, live birth rate was 43.31% in twice-cryopreserved group. After PSM,108 pairs of patients were generated for comparison. The clinical pregnancy rate, live birth rate or miscarriage rate was not significantly different between two groups. Logistic regression analysis indicated that double vitrification-warming procedures did not affect FET outcomes in terms of clinical pregnancy rate (OR 0.83, 95%CI 0.47-1.42), live birth rate (OR 0.93, 95%CI 0.54-1.59), miscarriage rate (OR 0.72 95%CI 0.28-1.85). Furthermore, the pregnancy complications rate, gestational age or neonatal abnormalities rate between two groups was also comparable, while twice vitrification-warming procedures might increase the macrosomia rate (19.6% vs. 6.3%, P = 0.05). Conclusion Transfer of double vitrified-warmed embryo at cleavage stage and subsequent blastocyst stage did not affect live birth rate and neonatal abnormalities rate, but there was a tendency to increase macrosomia rate, which needs further investigation.

The Impact of the Time Interval Between Cycles on Pregnancy Outcome of Ovulation Induction Cycle Intrauterine Artificial Insemination

ObjectiveThe objective of this study was to estimate whether the time interval between two intrauterine inseminations (IUI) treatments needs to be extended by one menstrual cycle or more in patients undergoing successive cycles of ovulation stimulation, and whether this will have an impact on the clinical pregnancy rate (CPR).Study DesignRetrospective cohort study.Study siteThe study site was the reproductive medicine center of a teaching hospital.Patient(s)The subjects were women and their husbands who received two or more intrauterine insemination in our reproductive medicine center due to mild infertility in the period from January 2017 to December 2019. Patients were divided into 2 groups according to the number of days between the last menstrual day(LMD)and the previous IUI operation day(POD), continuous group (the time from the LMD to POD ≤ 34 days) and delayed group (the time from the LMD to POD ≥ 35 days). We excluded cycles with intervals of more than 180 days.In order to avoid the inclusion of multiple repeat cycles for the same couple, only the first two cycles of IUI treatment in the same couple were allowed to be included in this study. That is, when they failed the first IUI cycle, they were given a second IUI treatment.Intervention(s)No intervention.Main Outcome Measure(s)A total of 550 cycles met the inclusion criteria, and 374 (68.0%) cycles met the inclusion criteria for the continuous group,the remaining 176 (32.0%) cycles with at least one or more menstruations between two IUI cycles were included in the delayed group.The primary outcome measure was clinical pregnancy rate (CPR), with secondary outcomes including abortion rate. Differences in clinical pregnancy rate (CPR)、abortion rate were compared between the two groups.ResultThere was no significant difference between the continuous group and the delayed group in female age, male age, infertility duration, infertility type, female BMI, endometrial classification, endometrial thickness, semen volume before treatment, sperm density before treatment, percentage of forward motile sperm before treatment, sperm density after treatment, and percentage of forward motile sperm after treatment. There were no statistical differences between the delayed group vs continuous group regarding the clinical pregnancy rate (20.5 % vs 21.9 %) and abortion rate (27.8% vs 22.0%)（P>0.05）. The above factors were included for binary logistic regression analysis. It was found that the increase of endometrial thickness promoted the clinical pregnancy rate, which was statistically significant (OR=1.205, 95% CI 1.05-1.384,P=0.008). Compared with primary infertility, secondary infertility can promote the improvement of clinical pregnancy rate, which is statistically significant (OR=2.637,95%CI 1.313-5.298,P=0.006). The effect of time interval between IUI on clinical pregnancy was not statistically significant (OR=1.007,95% CI 0.513-1.974,P=0.985).ConclusionsOverall, prolonging the interval between two IUI did not significantly improve pregnancy outcomes. Unless there are clear clinical indications, it is not necessary to deliberately prolong the interval between two treatments.

Stress, anxiety, and depression in infertile couples are not associated with a first IVF or ICSI treatment outcome

Background Psychological distress may exert a negative influence on reproductive function of couples at reproductive age. Couples seeking assisted reproductive technology (ART) treatment may have a higher prevalence of psychological distress than fertile couples. However, whether psychological distress is associated with the outcome of ART treatment remains unknown. We aimed to investigate the association of pre-treatment psychological distress and clinical pregnancy rate among infertility couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Methods This nested case-control study was conducted based on women who underwent their first fresh IVF or ICSI cycle in the Jiangsu Birth Cohort Study (JBC) between November 2015 and January 2019. A total of 150 women who did not obtain clinical pregnancy after first IVF or ICSI fresh embryo transfer were identified as cases, and a total of 300 age matched women who obtained clinical pregnancy were identified as controls. Conditional logistic regression analyses were used to investigate the association between psychological distress and the outcome of first IVF or ICSI treatment, adjusting for multiple potential confounders. Results No statistically significant association was observed between score of maternal symptoms of psychological distress and clinical pregnancy. Adjusted ORs of logistic regression were 1.00 (95% CI 0.97-1.03) for anxiety, 0.98 (95% CI 0.95-1.02) for depression, and 0.98 (95% CI 0.95-1.01) for perceived stress, respectively. When treat depression and anxiety as categorical variables, 62 (13.8%) were classified as clinical depression, 11 (2.4%) were classified as clinical anxiety, among 450 women in the present study. Psychological distress symptoms were also not associated with clinical pregnancy rate. Adjusted ORs of logistic regression were 0.27 (95% CI 0.03-2.33) for anxiety, 0.88 (95% CI 0.46-1.68) for depression, respectively. Conclusions Our findings firstly indicated that psychological distress experienced prior to IVF/ICSI treatment was not associated with clinical pregnancy.

Impact of Luteinized Unruptured Follicles on Clinical Outcomes of Natural Cycles for Frozen/Thawed Blastocyst Transfer

ObjectiveTo investigate the impact of luteinized unruptured follicles (LUF) on clinical outcomes of frozen/thawed embryo transfer (FET) of blastocysts.MethodsIn this retrospective cohort study, 2,192 patients who had undergone blastocyst FET treatment with natural cycles from October 2014 to September 2017 were included. Using propensity score matching, 177 patients diagnosed with LUF (LUF group) were matched with 354 ovulating patients (ovulation group). The LUF group was further stratified by the average LH peak level of 30 IU/L. Clinical pregnancy rate and live birth rate were retrospectively analyzed between the LUF and ovulation groups, as well as between LUF subgroups.ResultsAfter propensity score matching, general characteristics were similar in the LUF and ovulation groups. Clinical pregnancy rate in the LUF group was significantly lower than that in the ovulation group (47.46 vs. 58.76%, respectively, adjusted P = 0.01, OR 0.60, 95% CI 0.42–0.87). However, no significant difference was detected in live birth rate, although it was lower in the LUF group (43.50 vs. 50.00%, adjusted P = 0.19, OR 0.76, 95% CI 0.51–1.14). In the LUF subgroup analysis, both clinical pregnancy rate (43.02 vs. 62.30%, adjusted P = 0.02, OR 0.45, 95% CI 0.23–0.87) and live birth rate (37.21 vs. 59.02%, adjusted P = 0.01, OR 0.40, 95% CI 0.20–0.78) in the LH &lt;30 IU/L subgroup were significantly lower than those in the LH ≥30 IU/L subgroup.ConclusionLUF negatively affected clinical outcomes of frozen/thawed embryo transfer of blastocysts, particularly when the LH surge was inadequate.