Hyaluronic acid-enriched transfer medium for frozen embryo transfer: a randomized, double-blind, controlled trial.

OBJECTIVE: To compare the effects of hyaluronic acid (HA)-enriched transfer medium versus standard medium on live birth rate after frozen embryo transfer (FET). DESIGN: Randomized, double-blind, controlled trial. SETTING: Two tertiary fertility centers. PATIENT(S): Infertile women aged <43 years at the time of in vitro fertilization undergoing FET. INTERVENTION(S): The women were randomly assigned to 2 groups in a 1:1 ratio. The HA group used EmbryoGlue (Vitrolife, Gothenburg, Sweden) with an HA concentration of 0.5 mg/mL, while the control group used supplemented G-2 (Vitrolife) medium with an HA concentration of 0.125 mg/mL. MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): Five hundred fifty women were recruited from April 2016 to April 2018 and included in the intention-to-treat analysis. Eight women in the HA group and 5 women in the control group did not undergo FET because the embryos did not survive on thawing. One woman in the HA group cancelled FET because of fever. One woman in the HA group withdrew and received conventional medium. The 2 groups were similar in demographic characteristics. The live birth rates in the HA group and the control group were comparable (25.5% vs. 25.8%; relative risk 0.99; 95% confidence interval 0.74-1.31). The other clinical outcomes were also similar between the 2 groups. Logistic regression showed that the type of transfer medium was not associated with live birth. CONCLUSION(S): The use of HA-enriched transfer medium does not improve the live birth rate of FET compared with standard medium. TRIAL REGISTRATION NUMBER: NCT02725827 (ClinicalTrials.gov).

Performance of ovarian response prediction index (ORPI) in predicting ovarian response and livebirth in the in-vitro fertilisation cycle using a standard stimulation with corifollitropin alpha in a GnRH antagonist protocol.

The objective of this study was to evaluate the performance of ovarian response prediction index (ORPI) in predicting ovarian response and livebirth of women undergoing their first in-vitro fertilisation (IVF) cycle. This is a retrospective analysis of 285 women from 2013 to 2016. The outcome measures were area (AUC) under the receiver-operator characteristic (ROC) curves for prediction of excessive and poor response, livebirth in the fresh cycle and cumulative livebirth. The ORPI was significantly correlated with the oocyte number. For prediction of excessive response, AUC for ORPI was comparable to AMH and significantly higher than AFC and female age. At a cut-off of 0.42, ORPI has a sensitivity and specificity of 84% and 77% respectively for prediction of excessive response. For prediction of poor response, AUC for ORPI was significantly higher than AFC, AMH and female age. At a cut-off of 0.12, ORPI has a sensitivity of 69% and specificity of 89% respectively for prediction of poor response. For prediction of livebirth, AUCs of ORPI were not significantly different from AFC and female age. Therefore, ORPI is not a good predictor of livebirth. Its prediction of excessive and poor ovarian response is comparable to that of serum AMH.

Ovarian response and cumulative live birth rate of women undergoing in-vitro fertilisation who had discordant anti-Mullerian hormone and antral follicle count measurements: a retrospective study.

OBJECTIVE: To evaluate ovarian response and cumulative live birth rate of women undergoing in-vitro fertilization (IVF) treatment who had discordant baseline serum anti-Mullerian hormone (AMH) level and antral follicle count (AFC). METHODS: This is a retrospective cohort study on 1,046 women undergoing the first IVF cycle in Queen Mary Hospital, Hong Kong. Subjects receiving standard IVF treatment with the GnRH agonist long protocol were classified according to their quartiles of baseline AMH and AFC measurements after GnRH agonist down-regulation and before commencing ovarian stimulation. The number of retrieved oocytes, ovarian sensitivity index (OSI) and cumulative live-birth rate for each classification category were compared. RESULTS: Among our studied subjects, 32.2% were discordant in their AMH and AFC quartiles. Among them, those having higher AMH within the same AFC quartile had higher number of retrieved oocytes and cumulative live-birth rate. Subjects discordant in AMH and AFC had intermediate OSI which differed significantly compared to those concordant in AMH and AFC on either end. OSI of those discordant in AMH and AFC did not differ significantly whether either AMH or AFC quartile was higher than the other. CONCLUSIONS: When AMH and AFC are discordant, the ovarian responsiveness is intermediate between that when both are concordant on either end. Women having higher AMH within the same AFC quartile had higher number of retrieved oocytes and cumulative live-birth rate.

Cumulative live-birth rate in women with polycystic ovary syndrome or isolated polycystic ovaries undergoing in-vitro fertilisation treatment.

PURPOSE: This retrospective cohort study evaluated the cumulative live birth rate in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovaries (PCO) undergoing in-vitro fertilisation (IVF) treatment. METHODS: We studied 104 women with PCOS, 184 with PCO and 576 age-matched controls undergoing the first IVF treatment cycle between 2002 and 2009. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers combined after the same stimulation cycle. RESULTS: Women in both the PCOS (n = 104) and isolated PCO groups (n = 184) had higher ovarian response parameters compared to age-matched controls (n = 576), and higher rates of withholding fresh embryo transfer for risk of ovarian hyperstimulation syndrome (OHSS). The actual incidence of moderate to severe OHSS was significantly higher in the PCOS (11.5 %) but not the isolated PCO group (8.2%) compared to controls (4.9%). The live birth rates in the fresh cycle were comparable among the 3 groups, but the PCOS group had a significantly higher miscarriage rate compared to the other 2 groups. Cumulative live birth rate was significantly higher in the isolated PCO group (60.3%), but not the PCOS group (50.0%), compared to controls (47.5%). CONCLUSIONS: Women in the isolated PCO group, but not the PCOS group, had a significantly higher cumulative live birth rate compared to controls. This could be explained by the quantitative effect of the higher number of transferable embryos obtained per stimulation cycle, which is uncompromised by the unfavourable embryo competence otherwise observed in PCOS.

Role of baseline antral follicle count and anti-Mullerian hormone in prediction of cumulative live birth in the first in vitro fertilisation cycle: a retrospective cohort analysis.

OBJECTIVE: This retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle. METHODS: We studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle. RESULTS: Serum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH (0.646, 95% CI 0.616-0.675) and age (0.648, 95% CI 0.618-0.677) were slightly higher than that for AFC (0.617, 95% CI 0.587-0.647) in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone. CONCLUSION: Baseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the women's age.

Evaluating the performance of serum antimullerian hormone concentration in predicting the live birth rate of controlled ovarian stimulation and intrauterine insemination.

OBJECTIVE: To evaluate the role of serum antimullerian hormone (AMH) concentration in predicting live birth outcome in controlled ovarian stimulation and intrauterine insemination (IUI). DESIGN: Retrospective analysis. SETTING: Tertiary assisted reproduction unit. PATIENTS: 243 patients undergoing IUI treatment. INTERVENTION(S): Archived early follicular phase serum samples taken at the start of the first treatment cycle before ovarian stimulation were retrieved from patients undergoing IUI treatment. MAIN OUTCOME MEASURE(S): First-cycle and cumulative live birth rates. RESULT(S): Patients attaining a successful live birth, either in the first cycle or cumulatively after three cycles, had significantly higher serum AMH concentrations than those failing treatment. Serum AMH concentration correlated positively with antral follicle count (AFC) and duration of stimulation and inversely with maternal age, serum FSH concentration, and total dose of gonadotropin used. After controlling for age, body mass index, AFC, and FSH, AMH remained the only significant predictor of cumulative live birth. The area under the receiver operating characteristic curve was 0.668 in predicting cumulative live birth. Serum AMH concentration was significantly higher in overresponders. CONCLUSION(S): Serum AMH concentration was significantly higher in subjects with a live birth from the first cycle or after three cycles of stimulated IUI treatment compared with those failing treatment. Serum AMH concentration has a modest predictive value on ovarian overresponse.

A randomized double blind comparison of real and placebo acupuncture in IVF treatment.

BACKGROUND: Acupuncture has been used during IVF treatment as it may improve outcome, however, there are concerns about the true efficacy of this approach. This randomized double blind study aimed to compare real acupuncture with placebo acupuncture in patients undergoing IVF treatment. METHODS: On the day of embryo transfer (ET), 370 patients were randomly allocated to either real or placebo acupuncture according to a computer-generated randomization list in sealed opaque envelopes. They received 25 min of real or placebo acupuncture before and after ET. The endometrial and subendometrial vascularity, serum cortisol concentration and the anxiety level were evaluated before and after real and placebo acupuncture. RESULTS: The overall pregnancy rate was significantly higher in the placebo acupuncture group than that in the real acupuncture group (55.1 versus 43.8%, respectively, P = 0.038; Common odds ratio 1.578 95% confidence interval 1.047-2.378). No significant differences were found in rates of ongoing pregnancy and live birth between the two groups. Reduction of endometrial and subendometrial vascularity, serum cortisol concentration and the anxiety level were observed following both real and placebo acupuncture, although there were no significant differences in the changes in all these indices between the two groups. CONCLUSIONS: Placebo acupuncture was associated with a significantly higher overall pregnancy rate when compared with real acupuncture. Placebo acupuncture may not be inert. Trial registered with HKClinicalTrials.com: number HKCTR-236.

Randomized double-blind comparison of laser zona pellucida thinning and breaching in frozen-thawed embryo transfer at the cleavage stage.

OBJECTIVE: To compare the implantation and ongoing pregnancy rates of frozen-thawed embryo transfer (FET) using laser thinning with those of laser breaching of the zona pellucida (ZP). DESIGN: Double-blind randomized study. SETTING: A tertiary assisted reproduction unit. PATIENT(S): Infertile patients undergoing FET cycles. INTERVENTION(S): In the thinning group, more than a quarter of the ZP's outer half-diameter was removed by using a 1,480-nm noncontact laser, whereas a hole about 30 microm in size was created in the ZP in the breaching group. MAIN OUTCOME MEASURE(S): Implantation and ongoing pregnancy rates. RESULT(S): On the day of the FET, 180 patients were randomly divided into the thinning and breaching groups according to a computer-generated randomization list that was placed in sealed envelopes. The two groups were comparable in terms of demographic characteristics, ovarian response of the stimulated cycle, and quality of fresh and frozen-thawed embryos. The implantation and ongoing pregnancy rates of the thinning group were significantly higher than the corresponding rates of the breaching group but were similar to those of patients without ZP thinning or breaching. CONCLUSION(S): Laser ZP thinning is associated with significantly higher implantation and ongoing pregnancy rates in FET cycles compared with the case of laser ZP breaching.

A randomized double-blind controlled study of the efficacy of laser-assisted hatching on implantation and pregnancy rates of frozen-thawed embryo transfer at the cleavage stage.

BACKGROUND: Assisted hatching (AH) in fresh embryo transfer (ET) cycles increases the implantation and pregnancy rates, especially in women with a poor prognosis, repeated implantation failures and in older women. Little information exists in the literature regarding the role of AH in frozen-thawed embryo transfer (FET) cycles. METHODS: Embryos were cryopreserved at the cleavage stage. On the day of FET, 160 patients were randomized according to a computer-generated randomization list in sealed envelopes into the AH group and the control group. The patients and the clinicians were blinded to the group assigned. In the AH group, the outer half of the zona pellucida over a quarter of the diameter of zona was removed using a 1480 nm non-contact laser. RESULTS: The two groups were comparable in terms of demographic characteristics, ovarian response of the stimulated cycle and quality of fresh and frozen-thawed embryos. No differences in implantation, pregnancy and multiple pregnancy rates were found between the two groups. There was a non-significant trend of a higher implantation rate in the AH group when the zona thickness was > or = 16 mm. CONCLUSION: Laser AH did not improve the implantation rate of FET cycles and should not be performed routinely in all frozen-thawed embryos at the cleavage stage.

Is there any difference in pregnancy and implantation rates when nurses perform embryo transfer in an IVF-ET program?

A retrospective analysis of fresh in vitro fertilization treatment cycles and frozen embryo transfer (FET) cycles from mid-1995 to December 31, 1998, was undertaken. Nurses performed embryo transfer (ET) for government-funded cycles, whereas doctors performed ET for self-funded cycles. During the study period, fresh ET was performed in 1,165 treatment cycles. There were no significant differences in demographic data, ovarian responses and the number of embryos replaced between ET cycles performed by nurses and doctors. Pregnancy rates for ETs performed by nurses and doctors were 16.7 and 15.8% per transfer, respectively, whereas the corresponding implantation rates were 8.3 and 6.9%, respectively. Similar pregnancy and implantation rates were encountered in FET cycles whether ET was performed by nurses or doctors.

Oocyte and embryo quality in patients with excessive ovarian response during in vitro fertilization treatment.

PURPOSE: This study examined oocyte and embryo quality in patients having excessive ovarian responses during assisted reproduction treatment. METHODS: Two hundred and seventy-eight women of age <40 years using a long protocol of pituitary downregulation in their first intracytoplasmic sperm injection cycle indicated for severe male factors were retrospectively evaluated. Those with serum estradiol concentration on the day of HCG <10,000, 10,000-20,000, and >20,000 pmol/L were classified into Group A, Group B, and Group C, respectively. RESULTS: The percentage of metaphase II oocytes (85%), fertilization rate (60-66%), and distribution of blastomere number per embryo were similar among the three groups. The proportion of transferable embryos was not reduced in Group C when compared to those of Groups A and B. CONCLUSION: Excessive ovarian response does not compromise oocyte and embryo quality in humans. Freezing of all embryos is recommended in these patients in view of associated impaired endometrial receptivity.