Search

To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. Retrospective cohort. Large fertility clinic. A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether cured chronic endometritis (CE) from antibiotic treatment would be associated with a higher risk of spontaneous abortion in the following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.Design: Prospective cohort study.Setting: Tertiary reproductive medicine center.Patient(s): Patients with infertility who underwent a routine hysteroscopy underwent an IVF/ICSI stimulation between January 1, 2019, and December 31, 2020. Women with CE (N = 338) underwent antibiotic therapy, and the assisted reproductive outcomes were then compared with women without CE (N = 7,962).Intervention(s): Chronic endometritis was diagnosed through hysteroscopy and confirmed by histology and immunohistochemistry for CD138.Main Outcome Measure(s): Spontaneous abortion rate after the initial embryo transfer.Result(s): A total of 7,218 patients underwent embryo transfer, with 330 in the cured CE group and 6,888 in the non-CE group. Women with cured CE had a higher rate of spontaneous abortion than did those without CE (11.8% vs. 9.2%; crude odds ratio [OR], 1.32 [0.94, 1.86]), and this difference was statistically significant after adjusting for confounding variables (adjusted OR, 1.49 [1.01, 2.19]). The live birth rate was 43.9% in the cured CE group and 50.5% in the non-CE group (crude OR, 0.77 [0.62, 0.96]; adjusted OR, 0.73 [0.59, 0.92]). The incidence of clinical pregnancy did not differ significantly between the 2 groups (56.1% vs. 60.0%; crude OR, 0.85 [0.68, 1.06]; adjusted OR, 0.83 [0.66, 1.03]). Sensitivity analyses stratified by initial fresh- or frozen-thawed embryo transfer cycles resulted in similar results.Conclusion(s): Chronic endometritis cured with antibiotic therapy was associated with an increased risk of spontaneous abortion among women undergoing IVF/ICSI treatment. The interpretation of the findings is limited by a potential confounding bias. [ABSTRACT FROM AUTHOR]

Growth hormone, letrozole, and clomiphene citrate do not have US Food and Drug Administration approval for their use in in vitro fertilization (IVF) cycles. However, despite this fact, they often are used to augment the IVF cycle in women considered "low responders." Unfortunately, because of the problems inherent to recruiting women who have undergone several unsuccessful IVF treatment cycles, and their inevitable low live birth rate, studies involving adjuvants for women considered low responders to ovarian stimulation often are underpowered. This is compounded further by the difficulty in recruiting vulnerable women to a study with a placebo arm. Consequently, the evidence base for their use as adjuncts to IVF treatment may be limited, and consequently their use may be empirical rather than evidence based. This short narrative review describes the evidence for these "add-ons" for a patient with a low response to ovarian stimulation. It suggests that a woman with a low ovarian response will derive benefit from using growth hormone; with a reduction in the ovarian stimulation required for oocyte retrieval, collection of a greater number of oocytes, and improvement in the clinical pregnancy rate. Although there currently is insufficient evidence to state categorically that it leads to an increased chance of a live birth. In the same situation, clomiphene citrate and letrozole lead to a reduced requirement for gonadotropins before oocyte retrieval, but with no improvement in live birth rate for their use. [ABSTRACT FROM AUTHOR]

Objective: To estimate the probability of clinical or multiple pregnancy during ovulation induction (OI)/ovarian stimulation (OS).Design: Secondary analysis of two multicenter randomized clinical trials (combined).Setting: Multicenter.Patients: A total of 750 women with polycystic ovary syndrome and 900 women with unexplained infertility.Interventions: Ovulation induction/OS with either timed intercourse (polycystic ovary syndrome) or intrauterine insemination.Main Outcome Measures: Clinical and multiple pregnancy rates/cycle, cumulative pregnancy rates. Age, body mass index, parity, diagnosis, medication, markers of ovarian reserve, and ovarian response were considered in multivariable regression models for clinical, multiple, and cumulative pregnancy rates. Receiver operating characteristic curves were created for clinical and multiple pregnancy rates.Results: Younger patient and partner age, treatment type, lower body mass index, and medication dose were all associated with clinical pregnancy. Variables associated with multiple pregnancy included the abovementioned variables (except age), in addition to diagnosis, parity, higher antral follicle count, antimüllerian hormone levels, and ovarian response. Gonadotropin use was associated with multiple pregnancy, with progressively increasing odds ratios (cycles 1-4). Receiver operating characteristic curves indicated the model's predictive power to be fair for clinical pregnancy (areas under the curve [95% confidence interval {CI}]: 0.78 [0.75-0.81] for cycle 1 and 0.70 [0.64-0.75] for cycle 4) and good-to-excellent for multiple pregnancy (areas under the curve [95% CI]: 0.78 [0.72-0.84] for cycle 1 and 0.86 [0.78-0.93] for cycle 4). Partner age, lower medication dose, parity, antimüllerian hormone levels, and diagnosis were associated with cumulative pregnancy rates.Conclusions: Using the majority of the factors known to predict the outcome of OI/OS cycles, we constructed an easy-to-use formula that may predict individualized chances of clinical and multiple pregnancy for commonly used fertility treatments (https://pregnancyprediction.medicine.yale.edu/CalDirect.html).Clinical Trial Registration Numbers: Assessing Multiple Intrauterine Gestations after Ovulation Stimulation NCT01044862; PPCOSII NCT00719186. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether physicians' choice of ovarian stimulation protocol is associated with laboratory outcomes.Design: Retrospective cohort study.Setting: Single academic center.Patient(s): The subjects were 4,458 patients who completed more than one in vitro fertilization ovarian stimulation cycle within 1 year. On second stimulation, 49% repeated the same protocol and 51% underwent a different one.Intervention(s): Estradiol priming antagonist, antagonist +/- oral contraceptive pill priming, long luteal protocol, Lupron (Lupron [AbbVie Inc, North Chicago, IL]) stop protocol, and flare were compared. Logistic or linear regression with cluster robust standard errors to account for covariates and paired data was used.Main Outcome Measure(s): Oocytes collected (OC), fertilization rate, blastocyst progression (BP), usable embryos (UE), and euploid rate (ER).Result(s): First stimulation outcomes were comparable across all protocols for FR, BP, UE, and ER but were different for OC, after adjustment for covariates. For OC, the effect of switching protocols differed according to the type of the second stimulation. There was improvement in OC if the same stimulation was repeated, except for flare. In addition, there were slight, significant improvements in fertilization rate (difference in values or coefficient of 0.02; 95% confidence interval [CI], 0.004, 0.4) and UE (coefficient 1.25; 95% CI, 0.79, 1.72) when the same stimulation was repeated. There were no changes in BP (coefficient 0.03; 95% CI, -0.01, 0.08) or ER (coefficient 0.01; 95% CI, -0.04, 0.06) when protocols were changed. In a low-BP subgroup, greater improvement was seen when the same protocol was repeated (coefficient 0.03; 95% CI 0.01, 0.04).Conclusion(s): There was a slight but significant improvement in laboratory outcomes when the same stimulation protocol was repeated, so careful consideration should be made before switching stimulation protocols for the purpose of improving laboratory outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association, if any, between serum antimüllerian hormone (AMH) levels and probability of clinical pregnancy and spontaneous abortion (SAB) in the infertility setting.Design: Retrospective cohort study.Setting: Academic fertility center.Patient(s): A total of 1,861 gonadotropin stimulation/intrauterine insemination cycles stratified by AMH levels into 3 groups: Low, <25th percentile (<0.7 ng/mL); Middle, ≥25th and <75th percentile (0.7-4.4 ng/mL); and High, ≥75th percentile (≥4.5 ng/mL).Intervention(s): Intrauterine insemination after stimulation with gonadotropins.Main Outcome Measure(s): Cumulative probability of clinical pregnancy over a maximum of 3 and/or 6 cycles and SAB incidence risk rate (IRR). The Kaplan-Meier failure function (log rank test), Cox proportional hazards models, and multilevel mixed-effects Poisson regression models were performed to compare outcomes among the AMH groups.Result(s): Overall, in both unadjusted and adjusted models, the probability of achieving a clinical pregnancy was higher in the Middle and High AMH groups compared with that in the Low AMH group, both over 3 (hazard ratios [95% confidence interval], 1.55 [1.05-2.29] and 1.85 [1.22-2.81], respectively) and 6 (1.71 [1.17-2.48] and 2.12 [1.42-3.16], respectively) cycles. In the unadjusted models, the SAB IRR was higher among the Low AMH group (IRR [95% confidence interval], 2.17 (1.11-4.24]), with the relationship persisting after adjusting for age (1.83 [0.93-3.60]). When the SAB IRR were calculated separately for the subpopulations with and without polycystic ovary syndrome, a similar relationship was noted among the latter in the unadjusted (1.94 [0.97-3.88]) and adjusted (1.74 [0.86-3.49]) analyses.Conclusion(s): In women undergoing gonadotropin stimulation/intrauterine insemination, AMH appears to affect the probability of achieving a clinical pregnancy. A possible negative impact, independent of age, on the risk of SAB was also suggested. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety profile and the number of usable blastocysts on day 5 and on day 6 after treatment with an individualized dosing regimen of a follitropin delta and highly purified human menopausal gonadotropin (HP-hMG) for controlled ovarian stimulation.Design: Multicenter, open label, exploratory study.Setting: Reproductive medicine clinics.Patient(s): A total of 110 patients (aged 18-40 years).Intervention(s): Follitropin delta coadministered with HP-hMG, with follitropin delta dose fixed according to an established algorithm and HP-hMG dose at 75 IU when the follitropin delta starting dosage was <12 μg; 150 IU when follitropin delta dosage was 12 μg and weight <100 kg, and 225 IU when follitropin delta dosage was 12 μg and weight ≥100 kg (dosage adjustments confined to HP-hMG only).Main Outcome Measure(s): Mean number of good-quality blastocysts obtained at day 5 and day 6 as well as the proportion of women with ovarian hyperstimulation syndrome (OHSS).Result(s): A cohort study was compared with the follitropin delta group from the Evidence-based Stimulation Trial with Human Recombinant Follicle-Stimulating Hormone in Europe and Rest of World 1 (ESTHER-1) study. Even when stratified by age, a statistically significantly higher mean in the number of oocytes retrieved and number of good-quality blastocysts was observed in this study compared with the ESTHER-1 trial in which follitropin delta was used alone. The rate of patients triggered with a gonadotropin-releasing hormone agonist was statistically significantly higher in our Menopur and Rekovelle Combined Study (MARCS) cohort (43%) when compared with the rates reported in the follitropin delta cohort in the ESTHER-1 study (2.3%). Incidence of any grade of OHSS was 9.3% in the present study compared to 2.6% in follitropin delta group from ESTHER-1 trial. No cases of moderate or severe OHSS were observed in our study compared with 1.4% in the follitropin delta group of ESTHER-1.Conclusion(s): Optimizing the ovarian response during in vitro fertilization employing a mixed protocol of individualized dosing of follitropin delta and HP-hMG resulted in a statistically significant number of usable blastocysts on days 5 and 6 with an increased risk of mild OHSS, which did not require medical intervention or hospitalization.Clinical Trial Registration Number: NCT03483545. [ABSTRACT FROM AUTHOR]

Objective: To compare clinical and ongoing pregnancy after natural cycle (NC) intrauterine insemination (IUI) versus ovarian stimulation (OS) IUI in ovulatory women undergoing therapeutic donor insemination (TDI).Design: Retrospective cohort.Setting: Single infertility center.Patient(s): A total of 76,643 IUI cycles in patients treated with intrauterine insemination were examined. Women undergoing TDI in the absence of diagnosed female factor infertility were included.Intervention(s): NC TDI or OS TDI with either clomiphene citrate or letrozole.Main Outcome Measure(s): Clinical and ongoing pregnancies were analyzed by generalized estimating equations adjusting for age, body mass index, total motile sperm at time of insemination and cycle number. Ongoing multiple gestations were examined as a secondary outcome.Result(s): Six thousand one hundred ninety-two TDI cycles from 2,343 patients (711 patients without repeated IUI cycles) met inclusion criteria and were available for analysis (3,837 NC and 2,355 OS). There was no difference in mean age between the two groups (NC, 34.2 years vs. OS, 34.3 years). Probability of clinical and ongoing pregnancy was higher in the OS cohort compared with the NC cohort (OS, 22.4% vs. NC, 18.7% and OS, 15.4% vs. NC, 14.9%, respectively). However, OS significantly increased ongoing multiple gestations (OS, 10.8% vs. NC, 2.4%).Conclusion(s): Ovarian stimulation in TDI cycles resulted in a <4% increase in clinical and <1% increase in ongoing pregnancy, and more than fourfold increase in ongoing multiple gestations. Natural cycle IUI should be considered as a first-line treatment for ovulatory women who need donor insemination. [ABSTRACT FROM AUTHOR]

Objective: To study the association of endometrial thickness (EMT) with live birth rates (LBR) in ovarian stimulation with intrauterine insemination (OS-IUI) treatments for unexplained infertility.Design: Prospective cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial.Setting: Multicenter randomized controlled trial.Patients: A total of 868 couples with unexplained infertility (n=2,459 cycles).Interventions: OS-IUI treatment cycles (n = 2,459) as part of the AMIGOS clinical trial.Main Outcome Measures: Live birth rates; unadjusted and adjusted risk ratios (RR) for live birth by EMT category, calculated using generalized estimating equations.Results: The overall mean EMT on day of human chorionic gonadotropin administration in cycles with a live birth was significantly greater than in those without. Compared to the referent EMT group of 9 to 12 mm, the unadjusted RR for live birth for the EMT groups of ≤5 and 6-8 were 0.48 and 0.92, respectively. The test for trend indicated evidence of decreasing LBR with decreasing EMT. After adjustment for ovarian stimulation medication, a linear trend was no longer supported. Stratified analyses revealed no differences in associations by treatment group.Conclusions: In OS-IUI for unexplained infertility, higher LBR are observed with increasing EMT; however, EMT is not significantly associated with LBR when adjusted for OS treatment type. Appreciable LBR are seen at all EMT, even those of ≤5 mm, suggesting that OS-IUI cycles should not be canceled for thin endometrium.Clinical Trial Registration Number: NCT01044862. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk of ectopic pregnancies (EPs) for fresh cycles according to different ovarian stimulation protocols.Design: Registry-based retrospective cohort study.Setting: Not applicable.Patient(s): A total of 68,851 clinical pregnancies after fresh single embryo transfer between 2007 and 2015.Intervention (s): None MAIN OUTCOME MEASURE(S): Ectopic pregnancies. Odds ratios and 95% confidence intervals for EPs were calculated by using generalized estimating equations adjusted for potential maternal and treatment characteristics.Result(s): Among 68,851 clinical pregnancies, 1,049 (1.46%) cases of EP were reported. Compared with natural cycles, all ovarian stimulation protocols were associated with a significantly increased risk of EP. Ovarian stimulation with clomiphene (CC) demonstrated the highest odds ratios for EPs. Significant associations between ovarian stimulation protocols and EP compared with natural cycles were prominent when the number of retrieved oocytes was low (1-3) to moderate (4-7), but there were no significant associations when the number of retrieved oocytes was high (≥8).Conclusion(s): Ovarian stimulation protocols were significantly associated with an increased risk of EP. In particular, ovarian stimulation with CC had the highest risk of EP compared with other stimulation protocols. Further studies are essential to investigate possible confounding factors for different ovarian stimulation protocols, especially CC, and the risk of EP. [ABSTRACT FROM AUTHOR]

Objective: To describe a computer algorithm designed for in vitro fertilization (IVF) management and to assess the algorithm's accuracy in the day-to-day decision making during ovarian stimulation for IVF when compared to evidence-based decisions by the clinical team.Design: Descriptive and comparative study of new technology.Setting: Private fertility practice.Intervention(s): None.Patient(s): Data were derived from monitoring during ovarian stimulation from IVF cycles. The database consisted of 2,603 cycles (1,853 autologous and 750 donor cycles) incorporating 7,376 visits for training. An additional 556 unique cycles were used for challenge and to calculate accuracy. There were 59,706 data points. Input variables included estradiol concentrations in picograms per milliliter; ultrasound measurements of follicle diameters in two dimensions in millimeters; cycle day during stimulation and dose of recombinant follicle-stimulating hormone during ovarian stimulation for IVF.Main Outcome Measure(s): Accuracy of the algorithm to predict four critical clinical decisions during ovarian stimulation for IVF: [1] stop stimulation or continue stimulation. If the decision was to stop, then the next automated decision was to [2] trigger or cancel. If the decision was to return, then the next key decisions were [3] number of days to follow-up and [4] whether any dosage adjustment was needed.Result(s): Algorithm accuracies for these four decisions are as follows: continue or stop treatment: 0.92; trigger and schedule oocyte retrieval or cancel cycle: 0.96; dose of medication adjustment: 0.82; and number of days to follow-up: 0.87. These accuracies are for first iteration of the algorithm.Conclusion(s): We describe a first iteration of a predictive analytic algorithm that is highly accurate and in agreement with evidence-based decisions by expert teams during ovarian stimulation during IVF. These tools offer a potential platform to optimize clinical decision making during IVF. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the purpose of ovarian stimulation (oocyte cryopreservation [OC] versus in vitro fertilization (IVF) is associated with perceived stress before or after ovarian stimulation; and whether perceived stress is associated with ovarian stimulation outcomes.Design: Prospective cohort study.Setting: Academic practice.Patients: Women undergoing their first ovarian stimulation cycle as part of a randomized clinical trial, the Learning from Online Video Education (LOVE) study (NCT02979990).Interventions: Questionnaire before and after ovarian stimulation.Main Outcome Measures(s): Perceived stress scale (PSS) scores before and after stimulation. The number of oocytes collected was a secondary measure.Results: After adjustment for age, income, race, education, financial assistance, and fertility diagnosis, the indication for treatment (IVF vs. OC) was a significant predictor of pretreatment PSS scores. IVF participants had higher pretreatment scores (18.01 ± 6.43) than did OC participants (15.62 ± 5.61). Posttreatment PSS scores did not differ between the two groups. IVF participants experienced a decrease of 0.85 ± 2.34 points in PSS scores after treatment, whereas OC participant scores were stable over time. The trajectory of PSS scores differed between the two groups and neared significance. Financial support was a significant predictor of pretreatment and posttreatment PSS scores for the entire cohort. Neither pretreatment nor posttreatment PSS was predictive of the number oocytes collected.Conclusion: Compared with OC patients, IVF patients have higher stress levels, which decrease after ovarian stimulation. Perceived stress does not affect oocyte yield. [ABSTRACT FROM AUTHOR]

Elucidation of multiple waves of antral ovarian follicular development during the menstrual cycle has challenged traditional concepts of female reproductive physiology and foundations of assisted reproductive therapies. Approximately two-thirds of women develop two follicle waves throughout an interovulatory interval and the remainder exhibit three waves of follicle development. Major and minor waves of follicle development have been observed. Major waves are those in which a dominant follicle develops; dominant follicles either regress or ovulate. In minor waves, physiologic selection of a dominant follicle is not manifest. Knowledge of waves of antral follicular development has led to the global adoption of novel ovarian stimulation strategies in which stimulation can be initiated at various times throughout the cycle. Random-start and luteal-phase ovarian stimulation regimens have had important clinical applications for women requiring urgent oocyte or embryo cryopreservation for fertility preservation prior to chemotherapy. Ovarian stimulation twice in the same cycle, referred to as double stimulation, may be used to optimize clinical outcomes in women with a poor ovarian response to stimulation as well as in those requiring fertility preservation before chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of corifollitropin alfa in improving the success of IVF.Design: Systematic review and meta-analysis.Setting: Not applicable.Patient(s): Infertile women undergoing conventional IVF or intracytoplasmic sperm injection (ICSI).Intervention(s): Randomized controlled trials (RCTs) of infertile women undergoing a single IVF/ICSI cycle with either corifollitropin alfa or a conventional ovarian stimulation protocol based on daily injections. The review protocol was registered in PROSPERO before starting the data extraction (CRD42018088605).Main Outcome Measure(s): Primary outcomes were live birth rate and/or ongoing pregnancy rate. Clinical pregnancy rate, miscarriage rate, multiple pregnancies, number of oocytes and embryos obtained, cancellation rate, and rate of ovarian hyperstimulation syndrome and ectopic pregnancy were considered as secondary outcomes.Result(s): Eight randomized controlled trials were included; 2,345 women were assigned to the intervention group and 1,995 to the control group. The analysis of 4,340 IVF cycles did not reveal any difference in live birth rate and/or ongoing pregnancy rate between groups (risk ratio [RR], 0.92; 95% confidence interval [CI], 0.80-1.05). Similarly, no difference was found in clinical pregnancy rate (RR, 0.96; 95% CI, 0.88-1.05; I2 = 0%), miscarriage rate (RR, 0.94; 95% CI, 0.71-1.25; I2 = 0%), or multiple pregnancy rate (RR, 1.22; 95% CI, 0.99-1.50; I2 = 0%). Also, the rates of cycle cancellation, ovarian hyperstimulation syndrome, and ectopic pregnancy were similar in both groups. Sensitivity and subgroup analyses did not provide statistical changes to pooled results.Conclusion(s): Corifollitropin alfa seems to be an alternative for daily recombinant FSH injections in normal and poor responder patients undergoing ovarian stimulation in IVF/ICSI treatment cycles. [ABSTRACT FROM AUTHOR]

Objective: To assess in vitro fertilization (IVF) and pregnancy outcomes in patients having their first frozen embryo transfer (FET) after a freeze-all cycle versus similar patients having their first fresh embryo transfer (ET).Design: Retrospective cohort study.Setting: None.Patient(s): Registry data on 82,935 patient cycles from the Society for Assisted Reproductive Technology (SART).Intervention(s): All first fresh autologous IVF cycles were analyzed and compared to first FET cycles after a freeze-all first IVF stimulation. The cycles were subdivided into cohorts based upon the number of oocytes retrieved (OR): 1-5 (low), 6-14 (intermediate), and 15+ (high responders). Univariate analyses were performed on cycle characteristics, and multivariable regression analyses were performed on outcome data.Main Outcome Measure(s): Clinical pregnancy rate (CPR) and live-birth rate (LBR).Results: Of the 82,935 cycles analyzed, 69,102 patients had their first fresh transfer, and 13,833 had a first FET. High responders were found to have a higher CPR and LBR in the FET cycles compared with the fresh ET cycles (61.5 vs. 57.4%; 52.0 vs. 48.9%). In intermediate responders, both CPR and LBR were higher after fresh ET compared with FET (49.6% vs. 44.2%; 41.2 vs. 35.3%). Similarly, in low responders, CPR and LBR were higher after fresh compared with FET (33.2% vs. 15.9%; 25.9% vs. 11.5%).Conclusion(s): A freeze-all strategy is beneficial in high responders but not in intermediate or low responders, thus refuting the idea that freeze-all cycles are preferable for all patients. [ABSTRACT FROM AUTHOR]

Objective: To determine whether live birth rates differ by type of endometrial preparation in frozen embryo transfer (FET) cycles.Design: Retrospective cohort study.Setting: Academic fertility center.Patient(s): Reproductive-aged women undergoing autologous vitrified-warmed blastocyst FETs.Intervention(s): Comparison of two methods of endometrial preparation: programmed FET (known as group A: luteal phase GnRH agonist suppression, oral E2, and IM P starting 5 days before ET) versus unstimulated FET (known as group B: hormone and ultrasound monitoring for follicle collapse to time transfer).Main Outcome Measure(s): Live birth rates in group A and group B.Result(s): Group A consisted of 923 cycles, and group B consisted of 105. When stratified by age at transfer, there was no difference in any of the measured outcomes, including live birth rates in adjusted models (adjusted odds ratio 1.0, 95% confidence interval 0.6-1.5), except in patients older than 40 years. These patients in group B had a 100% failure rate (n = 6).Conclusion(s): In most women, unstimulated endometrial preparation with luteal support before FET has similar success compared with exogenous hormone preparation. Women older than 40 years may benefit from programmed FETs owing to the challenges of increased cycle variability expected in that age group. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the freeze-all policy ensures a higher efficacy in terms of cumulative live birth rate (CLBR) in comparison with a conventional fresh/frozen embryo transfer (ET) approach in patients with normal ovarian response.Design: Retrospective, matched, multicenter cohort study.Setting: Private IVF centers.Patient(s): This study analyzed 564 completed IVF cycles in which an average of 12-18 oocytes were retrieved. In 435 cycles the conventional strategy was applied, with initial ET followed by frozen embryo replacements, whereas in 129 cycles the freeze-all policy was performed, with elective cryopreservation and deferred use of all viable embryos.Intervention(s): None.Main Outcome Measure(s): The primary endpoint was CLBR. The secondary endpoint was cumulative clinical pregnancy rate.Result(s): Overall, statistically comparable CLBRs were achieved in the fresh/frozen and freeze-all groups (45.5% vs. 53.5%). Stratification of data for age and number of retrieved oocytes confirmed the absence of differences between the two groups. In a subanalysis in which the day of ET and cryopreservation were taken into account, a similar outcome was achieved in cleavage-stage groups (45.6% vs. 46.4%), whereas when ET was performed at the blastocyst stage the CLBR was significantly higher in the freeze-all group (45.3% vs. 66.7%).Conclusion(s): Our CLBR analysis indicates that clinical performance of the freeze-all policy is equivalent to that of the conventional strategy when ET is carried out at the cleavage stage. However, it seems to be superior if associated with cryopreservation and transfer at the blastocyst stage. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of a poor quality embryo (PQE) during double ET (DET) with a top quality embryo (TQE) on IVF outcome.Design: A review of prospectively collected data.Setting: Tertiary level fertility clinic.Patient(s): All patients undergoing blastocyst transfers as part of fresh IVF (n = 939) and frozen ET (n = 1,009) cycles performed between 2010 and 2016.Intervention(s): Single ET (SET) with TQE (group 1) was set as control and compared with outcomes for SET with PQE (group 2), DET with 2 TQEs (group 3), PQE plus TQE (group 4), and 2 PQE (group 5).Main Outcome Measure(s): Live births and multiple births.Result(s): The live birth rates for group 4 were statistically similar to group 1 during fresh IVF (26.5% vs. 33.7%; odds ratio [OR], 0.95; 95% confidence interval [CI] 0.53-1.7) and frozen ET (24.2% vs. 32.7%; OR, 0.75; 95% CI 0.48-1.2), although there was a trend for lower success. Conversely, multiple births were higher in group 4 for fresh IVF (19% vs. 4.7%; OR, 2.9; 95% CI 1.3-6.6) and frozen ET (10.3% vs. 2.6%; OR, 2.4; 95% CI 1.2-4.9). The live birth rates for group 2 (12.2% for fresh IVF and 14.6% for frozen ET) and group 5 (21.2% for fresh IVF and 14% for frozen ET) were lower and for group 3 were higher (40.8% for fresh IVF and 40.3% for frozen ET) when compared with group 1. Multiple births were significantly higher with DET.Conclusion(s): This study does not support DET with one PQE along with a TQE, when there is only one TQE and one or more PQEs available for fresh IVF or frozen ET. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of assisted reproductive technology (ART) on the offspring of Chinese population.Design: Retrospective, data-linkage cohort.Setting: Not applicable.Patient(s): Live births resulting from ART or natural conception.Intervention(s): None.Main Outcome Measure(s): Birth defects coded according to ICD-10.Result(s): Births after ART were more likely to be female and multiple births, especially after intracytoplasmic sperm injection (ICSI). ART was associated with a significantly increased risk of birth defects, especially, among singleton births, a significantly increased risk in fresh-embryo cycles after in vitro fertilization (IVF) and frozen-embryo cycles after ICSI. Associations between ART and multiple defects, between ART and gastrointestinal malformation, genital organs malformation, and musculoskeletal malformation among singleton births, and between ART and cardiac septa malformation among multiple births were observed.Conclusion(s): This study suggests that ART increases the risk of birth defects. Subgroup analyses indicate higher risk for both fresh and frozen embryos, although nonsignificantly for frozen embryos after IVF and for fresh embryos were presented with low power. Larger sample size research is needed to clarify effects from fresh- or frozen-embryo cycles after IVF and ICSI. [ABSTRACT FROM AUTHOR]

Objective: To identify the impact of embryo transfer time (total seconds from the loading of the transfer catheter to the expulsion of the embryo(s) into the uterine cavity) on clinical pregnancy (CPR), implantation (IR), and live birth (LBR) rates.Design: Retrospective cohort study.Setting: Academic hospital practice.Patient(s): A total of 465 women undergoing 571 frozen-embryo transfers with the use of cryopreserved blastocysts in a single academic institution from 2007 through 2014.Intervention(s): None.Main Outcome Measure(s): CPR, IR, and LBR.Result(s): The cohort was divided into tertiles according to transfer time in seconds (T1: 33-55; T2: 57-81; T3: 82-582) with mean (SD) transfer times of 47.4 (5.7), 67.1 (7.3), and 121.9 (55.1) seconds, respectively. Crude CPRs were 43.9%, 48.7%, and 48.7% among the respective tertiles, crude IRs were 36.9%, 39.9%, and 38.6%, and crude LBRs were 34.8%, 39.6%, and 36.0%. In univariate analysis, inferior cohort score, blood inside catheter, difficult mock transfer, and use of an outer sheath were negatively associated with CPR. No association was seen between physician performing the transfer (including fellows) and CPR. In multivariate regression, longer transfer time was not associated with CPR. With T1 as reference, adjusted odds ratios (95% confidence interval) were 1.28 (0.77-2.11) and 1.52 (0.85-2.71) for transfer time groups T2 and T3, respectively.Conclusion(s): After adjusting for potential confounders, this analysis found that contrary to commonly held belief, longer embryo transfer times do not negatively affect CPR, IR, or LBR. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of frozen embryo transfer on maternal and neonatal complications of singleton and twin pregnancies compared with fresh embryo transfer in women with polycystic ovary syndrome (PCOS).Design: A secondary analysis of a multicenter, randomized, controlled trial comparing live birth after frozen vs. fresh embryo transfer (FreFro-PCOS).Setting: Reproductive medicine centers.Patient(s): A total of 1,508 patients with a diagnosis of PCOS who were undergoing IVF were enrolled.Intervention(s): On day of oocyte retrieval, eligible patients were randomized to the fresh or frozen embryo transfer groups. Up to two embryos were transferred in both groups. All pregnancies were followed up until delivery.Main Outcome Measure(s): Gestational diabetes mellitus, pre-eclampsia, preterm birth, small for gestational age, and large for gestational age.Result(s): The risks of gestational diabetes mellitus, preterm birth, and small for gestational age were comparable between the frozen and fresh embryo transfer groups in both singleton and twin births. However, singleton infants born after frozen embryo transfer were more likely to be large for gestational age (25.2% vs. 17.5%; relative risk 1.44, 95% confidence interval 1.01-2.07, P=.044) than those born after fresh embryo transfer. Twin pregnancy after frozen embryo transfer had a higher risk of pre-eclampsia (12.0% vs. 2.8%; relative risk 4.31, 95% confidence interval 1.27-14.58, P=.009) than those after fresh embryo transfer.Conclusion(s): In women with PCOS, frozen embryo transfer resulted in an increased risk of large for gestational age in singleton pregnancy and a higher risk of pre-eclampsia in twin pregnancy.Clinical Trial Registration Number: NCT01841528. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of assisted hatching (AH) on live-birth rates in a retrospective cohort of patients undergoing first-cycle, autologous frozen embryo transfer (FET).Design: Longitudinal cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System between 2004 and 2013.Setting: Not applicable.Patient(s): Women who underwent first-cycle, autologous FET with (n = 70,738) and without (n = 80,795) AH reported from 2004 to 2013.Intervention(s): None.Main Outcome Measure(s): Live births.Result(s): Propensity matching was used to account for confounding covariates, and a logistic regression model was constructed to identify the predictors of live-birth rates in relationship to AH. In all first-cycle FETs, there was a slight but statistically significant decrease in the live-birth rate with AH compared with no AH (34.2% vs. 35.4%). In older patients and in the years 2012-2013 AH was associated with decreased live births. Live-birth rates and the number of AH cycles performed before FET vary by the geographic location of clinics.Conclusion(s): Assisted hatching slightly decreases the live-birth rate in first-cycle, autologous FET. Its use should be carefully considered, especially in patients 38 years old and older. Prospective, clinical studies are needed to improve our knowledge of the impact of AH. [ABSTRACT FROM AUTHOR]

Objective: To determine whether fresh embryo transfers are at a higher risk of abnormal implantation compared with frozen embryo transfers while accounting for the embryo stage at transfer.Design: Retrospective cohort study.Setting: Not applicable.Patient(s): We used data from the Society for Assisted Reproductive Technologies to identify all fresh and frozen autologous IVF cycles from 2004-2013 resulting in a positive pregnancy test. The cycles were parameterized into a four-level predictor of [1] fresh blastocyst transfer, [2] fresh non-blastocyst transfer, [3] frozen blastocyst transfer, and [4] frozen non-blastocyst transfer.Intervention(s): None.Main Outcome Measure(s): We examined a composite outcome of abnormal implantation, defined as biochemical pregnancy, ectopic/heterotopic pregnancy, and first-trimester pregnancy loss. Regression modeling was performed with repeated measures multivariable logistic regression, adjusted for age, parity, number of embryos transferred, infertility diagnosis, and calendar year of treatment.Result(s): Of 509,938 cycles analyzed, 31.8% resulted in abnormal implantation. Compared with a fresh blastocyst transfer, a fresh non-blastocyst transfer had a 22% increase risk of abnormal implantation, a frozen blastocyst transfer had a 36% increase risk, and a frozen non-blastocyst transfer had a 57% increase risk. When individual outcomes were analyzed, fresh embryo transfers had a lower risk of biochemical pregnancy and pregnancy loss but a higher risk for ectopic/heterotopic pregnancy.Conclusion(s): Fresh blastocyst transfers had the lowest overall risk of abnormal implantation but a higher risk of ectopic/heterotopic pregnancy. Although embryo cryopreservation is indicated in certain treatment cycles, elective embryo cryopreservation may not be the optimal strategy to adopt for all cycles. [ABSTRACT FROM AUTHOR]

Objective: To explore obstetric and perinatal outcomes in singleton pregnancies occurring as a result of fresh and thawed frozen embryo transfer using anonymized Human Fertilisation and Embryology Authority data.Design: Retrospective cohort study.Setting: Not applicable.Patient(s): Singleton births after IVF/intracytoplasmic sperm injection cycles in the United Kingdom (1991-2011).Intervention(s): A total of 112,432 cycles (95,911 fresh and 16,521 frozen) were analyzed using multivariate logistic regression to explore associations between type of embryo transferred (frozen vs. fresh) and obstetric and perinatal outcomes. Relative risks (RRs) and their 99.5% confidence intervals (CIs) were calculated using Stata 14 MP, adjusting for potential confounders.Main Outcome Measure(s): Birth weight.Result(s): The adjusted RR (99.5% CI) of low birth weight [0.73 (0.66-0.80)] and very low birth weight [0.78 (0.63-0.96)] were all lower after frozen embryo transfer; however, RR of having a high birth weight baby was higher [1.64 (1.53-1.76)]. There was no difference in RR of preterm birth [0.96 (0.88-1.03)], very preterm birth [0.86 (0.70-1.05)], and congenital anomalies [0.86 (0.73-1.01)].Conclusion(s): The findings of low birth and very low birth weight after thawed frozen embryo transfer are consistent with the literature and provide reassurance regarding the outcome of pregnancies after frozen embryo transfers. However, they highlight the possibility of high birth weight in these babies. Because these results are based on observational data, further evidence from randomized, controlled trials is needed before elective cryopreservation of all embryos is practiced in preference to the current practice of transfer of fresh embryos. [ABSTRACT FROM AUTHOR]

Objective: To identify blastocyst features independently predictive of successful pregnancy and live births with vitrified-warmed blastocysts.Design: Retrospective study.Setting: Academic hospital.Patient(s): Women undergoing a cycle with transfer of blastocysts vitrified using the Rapid-i closed carrier (n = 358).Intervention(s): None.Main Outcome Measure(s): Clinical pregnancy and live-birth rates analyzed using logistic regression analysis.Result(s): A total of 669 vitrified-warmed blastocysts were assessed. The survival rate was 95%. A mean of 1.7 ± 0.5 embryos were transferred. The clinical pregnancy, live-birth, and implantation rates were 55%, 46%, and 43%, respectively. The odds of clinical pregnancy (odds ratio [OR] 3.08; 95% confidence interval [CI], 1.88-5.12) and live birth (OR 2.93; 95% CI, 1.79-4.85) were three times higher with day-5 blastocysts versus slower-growing day-6 vitrified blastocysts, irrespective of patient age at cryopreservation. Blastocysts from multinucleated embryos were half as likely to result in a live birth (OR 0.46; 95% CI, 0.22-0.91). A four -fold increase in live birth was observed if an expanded blastocyst was available for transfer. The inner cell mass-trophectoderm score correlated to positive outcomes in the univariate analysis. The implantation rate was statistically significantly higher for day-5 versus day-6 vitrified blastocysts (50% vs. 29%, respectively).Conclusion(s): The blastocyst expansion grade after warming was predictive of successful outcomes independent of the inner cell mass or trophectoderm score. Delayed blastulation and multinucleation were independently associated with lower live-birth rates in frozen cycles. Implantation potential of the frozen blastocysts available should be included in the decision-making process regarding embryo number for transfer. [ABSTRACT FROM AUTHOR]

The way we practice assisted reproductive technology has changed over time. In many ways these changes have been positive as technology has improved, in vitro culture has improved, and embryo selection increasingly allows a single embryo transfer with high success rates and ever smaller multiple birth rates. However, our specialty has often been criticized for not being critical with respect to the acceptance of new technology. Although the outcome of interest seems clear (increasing birth of a healthy baby), the approach can be more complicated; and as there is a de-linking of egg retrieval and ET, and as costs and procedures increase, we should be rigorous about our acceptance of change. This is not to stall change but to encourage the same rigor and questioning of accepted dogma expected in other fields of medicine. An approach based on standard clinical study design to allow appropriate comparisons between patients, and to allow the most comprehensive information for patient counseling, is presented. [ABSTRACT FROM AUTHOR]

ET is a critical step in an assisted reproduction cycle. Over the past decade there has been an increasing trend to extending culture from cleavage-stage to blastocyst transfer. There has also been a trend to single ET and reporting the success of an assisted reproductive cycle as a cumulative live-birth rate after using both fresh and frozen embryos. There is low evidence that fresh blastocyst transfer is associated with improved live-birth rates compared with fresh cleavage-stage embryos. However, in the few studies that report cumulative pregnancy rates after fresh and frozen transfers, no significant difference was found. Cleavage-stage transfer is associated with greater numbers of embryos available for freezing, and blastocyst transfer is associated with increased number of cycles with no embryos to transfer. Further well-designed studies are warranted to evaluate the outcomes for blastocyst transfer including cumulative live-birth rate after fresh and frozen transfers, time to live birth, costs of the different transfer strategies, and perinatal mortality and severe perinatal morbidity. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of atosiban, given before transfer of frozen-thawed embryo to women with endometriosis (EMs).Design: A randomized, controlled clinical trial.Setting: University hospital and IVF center.Patient(s): One hundred twenty women with endometriosis undergoing frozen-thawed embryo transfer were randomly allocated into the atosiban treatment and the control groups. Another 120 women with infertility due to tubal factor were enrolled into a tubal factor group, to compare serum oxytocin (OT) and prostaglandin (PG)F2α levels and uterine contractions with the endometriosis group.Intervention(s): In the endometriosis treatment group, a single bolus (6.75 mg, 0.9 mL per vial) of atosiban was administrated before ET.Main Outcome Measure(s): Implantation rate and pregnancy rate.Result(s): Serum OT level (1.89 ± 0.33 vs. 1.66 ± 0.32 ng/L), PGF2α (2.83 ± 0.34 vs. 2.36 ± 0.35 ng/L) level, and uterine contractions (2.5 ± 1.2 vs. 1.8 ± 1.0 waves per minute) in the endometriosis group were all significantly higher than in the tubal factor group. The clinical pregnancy rate per cycle and implantation rate per transfer were 58.3% and 41.0%, respectively, in the atosiban treatment group, significantly higher than in the control group (38.3% and 23.4%, respectively).Conclusion(s): Women with endometriosis showed higher serum OT level, PGF2α level, and uterine contractions. Atosiban treatment before ET in endometriosis is effective in the priming of the uterus, suitable for embryo implantation. This is the first study to evaluate the effect of atosiban treatment in patients with endometriosis.Clinical Trial Registration Number: ChiCTR-IOQ-14005715. [ABSTRACT FROM AUTHOR]

Objective: To estimate birth weight differences between patients randomized to fresh or thawed ET.Design: Post hoc analysis of results from two similar randomized trials.Setting: Private fertility center.Patient(s): One hundred thirty-four first-time IVF patients, ages 18-40 years at oocyte retrieval, who had live birth.Intervention(s): Patients were randomly assigned to have either fresh blastocyst transfer or all bipronuclear oocytes frozen followed by thaw, extended culture, and blastocyst transfer in a subsequent cycle. Preimplantation genetic screening was not allowed.Main Outcome Measure(s): Mean birth weight.Result(s): After allowing for the contributions of multiple significant variables (gestational age at birth, the presence of a vanished twin, number of infants delivered) in multiple linear regression, the adjusted mean birth weight was 166 g (95% confidence interval, 43-290 g) lower after fresh blastocyst transfer when compared with transfer of blastocysts derived from thawed bipronuclear oocytes.Conclusion(s): Birth weights are lower in cycles with fresh blastocyst transfer after controlled ovarian stimulation than in transfers of frozen-thawed embryos in the absence of ovarian stimulation. This finding confirms similar results reported in many retrospective studies.Clinical Trial Registration Numbers: NCT00963625 and NCT00963079. [ABSTRACT FROM AUTHOR]

Objective: To study pregnancy outcomes between South Asian and Caucasian women undergoing frozen blastocyst transfer cycles.Design: Retrospective cohort study.Setting: Not applicable.Patient(s): Caucasian and South Asian patients undergoing frozen blastocyst transfer between January 2011 and December 2014.Intervention(s): Not applicable.Main Outcome Measure(s): Live birth rate.Result(s): A total of 196 Caucasian and 117 South Asian women were included in our study. Indians were on average 2.2 years younger than Caucasian women (34.9 vs. 37.1 years), and were more likely to be nulliparous (59% vs. 43%). All other baseline characteristics were similar. In women undergoing their first frozen ET cycle, implantation rate (49% vs. 47%), clinical pregnancy rate (PR; 54% vs. 49%), and live birth rate (43% vs. 43%) were similar between South Asians and Caucasians, respectively. In patients who underwent a prior fresh blastocyst transfer, the live birth rate was significantly lower in South Asian versus Caucasian women (21% vs. 37%).Conclusion(s): Our data demonstrate that IVF outcomes are better in frozen versus fresh cycles among South Asian women. The IVF clinics may wish to consider these findings when counseling South Asian patients about the timing of ET. [ABSTRACT FROM AUTHOR]

Clinics performing assisted reproductive technology (ART) procedures have collected data via registry and publicly reported pregnancy outcomes for more than 25 years. During this time, the practice of ART has changed considerably with frozen embryo transfer (FET) procedures contributing an increasing proportion of live births. Cycles initiated with the intent of embryo banking for the purpose of fertility preservation have been excluded from these public reports, because pregnancy outcomes are not immediately available. An unintended consequence of the common sense handling of fertility preservation has been that cycles performed with intentional short-term cryopreservation of all embryos for other indications have also been excluded from the report. Over the last few years, cryopreservation with short-term delayed transfer increasingly has been performed for reasons other than fertility preservation. The pregnancy outcomes of these cycles are expected within a reasonable time frame and should be transparently reported. The Society for Assisted Reproductive Technology has collaborated with the Centers for Disease Control and Prevention to “recapture” these cycles for the public reports. This recapture is done by linking the FET cycles to the stimulation cycles from which the embryos were derived and by changing the labels of the outcome success metrics. Stimulations using ART, initiated for the purpose of transferring embryos within 1 year will be included in the report despite any prospective intent to freeze all eggs or embryos. A positive outcome will be reported when a live birth results from the first embryo transfer following stimulation (“primary transfer”). Linkage of ovarian stimulation and egg-retrieval procedures to FET will also allow development of other success metrics to further benefit fertility patients. [ABSTRACT FROM AUTHOR]

Cryopreservation of human embryos is now a routine procedure in assisted reproductive technologies laboratories. There is no consensus on the superiority of any protocol, and substantial differences exist among centers in day of embryo cryopreservation, freezing method, selection criteria for which embryos to freeze, method of embryo thawing, and endometrial preparation for transfer of frozen-thawed embryos. In the past decade, the number of frozen-thawed embryo transfer cycles per started in vitro fertilization (IVF) cycle increased steadily, and at the same time the percentage of frozen-thawed embryo transfers that resulted in live births increased. Currently, cryopreservation of human embryos is more important than ever for the cumulative pregnancy rate after IVF. Interestingly, success rates after frozen-thawed embryo transfer are now nearing the success rates of fresh embryo transfer. This supports the hypothesis of so called freeze-all strategies in IVF, in which all embryos are frozen and no fresh transfer is conducted, to optimize success rates. High-quality randomized controlled trials should be pursued to find out which cryopreservation protocol is best and whether the time has come to completely abandon fresh transfers. [ABSTRACT FROM AUTHOR]

Epidemiologic studies have shown an increased rate of adverse perinatal outcomes, including small for gestational age (SGA) births, in fresh in vitro fertilization (IVF) cycles compared with frozen embryo transfer cycles. This increase is not seen in the donor oocyte population, suggesting that it is the peri-implantation environment created after superovulation that is responsible for these changes. During a fresh IVF cycle, multiple corpora lutea secrete high levels of hormones and other factors that can affect the endometrium and the implanting embryo. In this review, we discuss both animal and human data demonstrating that superovulation has significant effects on the endometrium and embryo. Additionally, potential mechanisms for the adverse effects of gonadotropin stimulation on implantation and placental development are proposed. We think that these data, along with the growing body of epidemiologic evidence, support the proposal that frozen embryo transfer should be considered preferentially, particularly in high responders, as a means to potentially decrease at least some of the adverse perinatal outcomes associated with IVF. [ABSTRACT FROM AUTHOR]

Recent dramatic increases in success rates with frozen–thawed embryo transfer (FET) are encouraging, as are numerous findings of several reduced risks with FET when compared with fresh transfer. These reduced risks include low birth weight and prematurity, among others. However, FET is also associated with increased risks of macrosomia and large for gestational age. There have been reports of greater implantation and pregnancy rates with FET than with fresh autologous embryo transfer, suggesting superior endometrial receptivity in the absence of ovarian stimulation. As cryo-technology evolves, there is potential for further increase in FET success rates, but for now it may be best to follow an individualized approach, balancing fresh transfer and embryo cohort cryopreservation options while considering patient characteristics, cycle parameters, and clinic success rates. [ABSTRACT FROM AUTHOR]

Objective: To assess the incidence of P elevation (PE) in natural cycles and evaluate its effect on frozen–thawed embryo transfer cycles performed in natural cycles (FET-NC). Study Design: Retrospective analysis. Setting: A tertiary assisted reproductive unit. Patient(s): Subfertile woman who did not conceive in their stimulated IVF cycle and underwent the first FET-NC cycle. Intervention(s): Achieved serum samples were assayed for P concentrations from the day of LH surge up to 3 days before the surge. The cutoff level of PE was defined as 5 nmol/L. Main Outcome Measure(s): Clinical and ongoing pregnancy rates. Result(s): The incidence of PE in natural cycles was 173 of 610 (28.4%). There were no significant differences in both clinical and ongoing pregnancy rates (39.0% vs. 37.3% and 32.5% vs. 31.7%) between those with vs. without PE on the day of LH surge. If PE lasted for 2 days or more, there was a significant reduction in the clinical pregnancy rate (39.4% vs. 20.7%). Using multivariate logistic regression, women's age, PE for 2 days or more, and the number of top-quality embryos were the significant factors for clinical pregnancy rates in FET-NC. Conclusion(s): The incidence of PE in FET-NC was similar to that in stimulated cycles. Progesterone elevation for 2 days or more before the LH surge impaired the clinical pregnancy rate of FET-NC, whereas PE on the day of LH surge only did not have such an adverse effect. [ABSTRACT FROM AUTHOR]

Objective: To analyze the incidence of ectopic pregnancies (EPs) in fresh and frozen/thawed cycles. Design: A retrospective cohort study on the incidence of EPs in all fresh IVF cycles from January 2002 until December 2012. This was compared with the incidence of tubal pregnancies in patients undergoing transfer of frozen/thawed embryos during the same time period. Setting: The IVF program at Fertility Center, AZ Jan Palfijn, Gent, Belgium. Patient(s): A total of 11,831 patients undergoing IVF (i.e., the entire population of the IVF Center) were retrospectively analyzed. Intervention(s): The IVF cycles, fresh IVF-ET, frozen/thawed ET. Laparoscopy for treatment of EP. Main Outcome Measure(s): Primary end point: incidence of EPs in both groups. Secondary end points: clinical pregnancy rate (PR), rate of EPs per clinical pregnancy. Result(s): In the fresh IVF cycle group, 10,046 patients underwent oocyte retrieval; 9,174 of them had an ET; 2,243 of these patients had a clinical pregnancy. Of these, 43 (0.47%) appeared to have an ectopic localization of their pregnancy. In the group of the patients undergoing frozen/thawed ET (1,785 patients) there were 467 pregnancies and 6 ectopic implants (0.34%). The incidence of the EPs per established clinical pregnancy was 1.92% for the fresh vs. 1.28% for the frozen/thawed cycles. Conclusion(s): No significant difference could be demonstrated on the incidence of EP in fresh IVF cycles vs. frozen/thawed cycles in a large cohort of patients. [ABSTRACT FROM AUTHOR]

Objective: To discern the potential effect of ovarian stimulation on implantation potential by comparing ongoing pregnancy rates from matched blastocysts in fresh and frozen-thawed single-embryo-transfer cycles. Design: Matched cohort study. Setting: Private fertility center. Patient(s): Ninety-three matched pairs of single-blastocyst transfer. Intervention(s): Fresh and frozen-thawed embryo transfers were matched on embryo parameters and patient age. Main Outcome Measure(s): Ongoing pregnancy at 10 weeks'' gestation. Result(s): The fresh and frozen-thawed groups did not differ significantly in blastocyst diameter, inner cell mass size, trophectoderm cell count, patient age, use of genetic screening, or presence of supernumerary embryos. The ongoing pregnancy rate was significantly greater in the frozen-thawed group than in the fresh group for transfers of day 6 blastocysts (54.3% vs. 17.1%, respectively), but not for day 5 blastocysts (60.9% vs. 56.5%, respectively). This resulted in the overall ongoing pregnancy rate to be significantly greater in the frozen-thawed group than in the fresh group (55.9% vs. 26.9%, respectively). Conclusion(s): Autologous day 6 blastocysts transferred in frozen-thawed cycles have significantly greater chance of viable implantation than morphologically equivalent embryos transferred in fresh cycles. This advantage appears to result from impaired implantation of day 6 blastocysts in fresh transfers after ovarian stimulation, suggesting that embryo-endometrium asynchrony is a major cause of impaired endometrial receptivity after ovarian stimulation. [Copyright &y& Elsevier]

Objective: To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. Design: Systematic review and meta-analysis. Setting: Centers for reproductive care. Patient(s): Infertility patient(s). Intervention(s): An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. Main Outcome Measure(s): The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. Result(s): We included three trials accounting for 633 cycles in women aged 27–33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. Conclusion(s): Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles. [ABSTRACT FROM AUTHOR]

Objective: To compare the reproductive outcome of three protocols for frozen ET treatment. Design: Retrospective follow-up study. Setting: Two public clinics and one private clinic. Patient(s): Four thousand four hundred seventy frozen ET cycles between 2006 and 2010. Intervention(s): Thawing of embryos and ET. Main Outcome Measure(s): Pregnancy test rate, clinical pregnancy rate, and pregnancy loss rate. Result(s): The natural cycle followed by P (NC + P) was used in 26% of cycles, the natural cycle with hCG (NC + hCG) in 10%, and the substituted cycle with estrogen and P (E + P) in 64% of cycles. The rate of transfers after thawing was similar in all groups (87.2%, 73.9%, and 87.2%, respectively). There was a significantly higher positive pregnancy test rate in the E + P (34.3%) and NC + hCG (35.5%) cycles as compared with the NC + P cycles (26.7%). However, the clinical pregnancy rate was similar in all groups (27.7%, 29.1%, and 24.3%, respectively). Moreover, no differences were seen between groups regarding the live-birth rate (20.1%, 23.5%, and 20.7%, respectively). A logistic regression analysis showed that the type of protocol was the only predictor of pregnancy loss, while age, irregular cycles, endometrial thickness, number, and quality of embryos transferred did not correlate to pregnancy loss. Conclusion(s): A higher positive pregnancy test rate was obtained in E + P frozen ET cycles in comparison with other protocols; however, due to an increased preclinical and clinical pregnancy loss, comparable clinical pregnancy, and delivery rates are reported for the three protocols. [ABSTRACT FROM AUTHOR]

Objective: To review a center''s experience with cryopreserved embryos generated from donor eggs and to analyze their long-term disposition. Design: Retrospective analysis of donor egg cycles with cryopreserved embryos. Setting: University-based IVF program. Patient(s): Eight hundred twenty-nine women undergoing ooctyte donation. Intervention(s): N/A. Main Outcome Measure(s): Factors affecting the decision regarding disposition of donor frozen embryo transfer (dFET) and the association between fresh and dFET cycles. Result(s): From January 2000 to December 2004, donor egg recipients underwent 829 fresh embryo transfer cycles that resulted in a 54% live birth rate. Of the 444 recipients who delivered, 177 (40%) also cryopreserved embryos at transfer; however, only 37 (21%) returned for a dFET by August 2009 and only 18 women had children from fresh and frozen transfers. In contrast, 128 of the 385 recipients who failed the fresh transfer (33%) cryopreserved embryos and 111 (87%) returned for a dFET. Of these, 44 had children from the dFET. Frozen cycle success rates between these recipient groups did not depend on fresh cycle outcome or prior parity. Conclusion(s): Donor oocyte recipients often initiate treatment with a desire to cryopreserve embryos for future use and family expansion. However, our data demonstrates that most recipients with a child from the fresh transfer do not return to use their cryopreserved embryos. Although fresh transfer success correlated with embryo disposition, it did not correlate with the outcome of thawed embryo transfer. [Copyright &y& Elsevier]