Objective:To determine if the novel cost-conscious and simplified Cardinal protocol could achieve noninferior clinical outcomes in planned oocyte cryopreservation (OC) cycles, compared with routine protocols. Design:Prospective noninferiority cohort study, nonrandomized. Subjects:Patients undergoing planned OC were prospectively recruited at a single academic institution between July 2023 and August 2024. Exposure:Participants self-selected between the routine protocols vs. the Cardinal protocol. All participants paid for their cycles out-of-pocket or using insurance. The Cardinal protocol is limited to 2 ultrasounds (baseline and stimulation day [SD] 9, no bloodwork, standardized follicle-stimulating hormone (FSH) dosing (antimüllerian hormone ≤ 4: 300 IU, antimüllerian hormone > 4: 225 IU), scheduled progestin start on SD6 in place of an antagonist, and autotrigger when ≥3 follicles are projected to be ≥18 mm. Routine protocols (antagonist, microdose flare) include up to maximum-dose gonadotropins, 5-6 ultrasounds, and 3-5 blood draws. Main Outcome Measures:The primary outcome was the number of mature metaphase II oocytes (MIIs) retrieved. Secondary outcomes included the total number of oocytes retrieved and cryopreserved, premature ovulation, ovarian hyperstimulation syndrome (OHSS), cycle cancellation, and postretrieval surgical complications. Total charges including the cost of medications were noted. A postcycle survey compared satisfaction and sociodemographic factors influencing patient choice between the Cardinal vs. routine protocols. Results:Of 118 total participants, 60 enrolled in Cardinal and 58 opted for routine. No significant differences (i.e., in age, body mass index, race/ethnicity) existed between groups. A total of 137 cycles (70 Cardinal and 67 routine) were compared. The mean difference in MIIs between groups was +1.08 (95% CI -1.1 to 3.27), demonstrating noninferiority of the Cardinal protocol. Premature ovulation did not occur in either group. The OHSS rates were lower in Cardinal (2.9% vs. 23%); no other significant differences in adverse events were noted. The median charge for a Cardinal cycle was $5,004 lower than that of routine protocols. Postcycle surveys (73% response rate) demonstrated higher satisfaction with Cardinal at 85% vs. 65%, driven by cost and convenience. Conclusions:The Cardinal protocol appears to be a noninferior option to routine protocols. It considerably reduced charges by $5,000 without a decrease in MIIs retrieved, making it a cost-conscious protocol that should be seriously considered for OC cycles. The Cardinal protocol was overall satisfactory for patients who selected this over the routine protocols, notably across diverse sociodemographic groups. Trial registration:NCT05842070; https://clinicaltrials.gov/study/NCT05842070.

Lay summary:In this study, we wanted to explore if adding gonadotropin agonist (GnRHa) to the standard use of human chorionic gonadotropin (hCG) for triggering egg maturation in in vitro fertilization (IVF) could be a more cost-effective option. What that means: Using hCG alone: Traditionally, hCG is the most common hormone used to trigger eggs to mature fully so that they can be collected for fertilization. Adding GnRHa: GnRHa is another medication that mimics a natural hormone produced by the brain. Adding this as a co-trigger may do better than just using hCG alone, by leading to more mature eggs and increasing live birth rates (LBRs). However, concerns about added costs and inconvenience remain. To address this, we created a cost model comparing LBRs and costs between the two strategies. Our analysis found that using this dual trigger increased LBRs by 13%, with a small cost increase of $175. For each 1% higher LBR, the added cost of using GnRHa + hCG was $13. Considering this minimal increase in cost relative to the overall high cost of IVF, using the dual trigger appears to be a cost-effective strategy to improve success rates for patients.

Purpose To evaluate the relative live birth rate and net cost difference between mosaic embryo transfer and an additional cycle of IVF with PGT-A for patients whose only remaining embryos are non-euploid.Methods A decision analytic model was designed with model parameters varying based on discrete age cutoffs (<35, 35-37, 38-39, 40-42, 43-44, >44). Model inputs included probabilities of successful IVF, clinical pregnancy, and live birth as well as costs of IVF with PGT-A, embryo transfer, live birth, amniocentesis, and dilation and curettage. All costs were modeled from the healthcare system perspective and adjusted for inflation to 2023 $USD. Model outcomes were sub-stratified by degree and type of mosaicism.Results For patients younger than 43, an additional cycle of IVF with PGT-A resulted in a higher relative live birth rate (<35, +20%; 35-37, +15%; 38-39, +17%; 40-42, +6%; average, +14.5%) compared to mosaic embryo transfer with an average additional cost of $16,633. For patients older than 42, mosaic embryo transfer resulted in a higher live birth rate (43-44, +5%; >44, +3%; average, +4%) while on average costing $9572 less than an additional cycle of IVF with PGT-A.Conclusion Mosaic embryo transfers are a superior alternative to an additional cycle of IVF with PGT-A for patients older than 42 whose only remaining embryos are non-euploid. Mosaic embryo transfers also should be considered for patients younger than 42 who are unable to pursue additional autologous IVF cycles. Counseling and care should be personalized to individual patients and embryos.

To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos. This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m2) category: normal weight (18.5–24.9), overweight (25–29.9) or obese (≥ 30). Underweight BMI (< 18.5) was excluded from the analysis. The primary outcome was live birth rate (LBR) and secondary outcome was clinical pregnancy rate (CPR), defined as presence of fetal cardiac activity on ultrasound. Absolute standardized differences (ASD) were calculated to compare descriptive variables and p-values and multivariable logistic regressions with generalized estimating equations (GEE) were used to compare pregnancy outcomes. 562 mNC-FET cycles were completed in 425 patients over the study period. Overall, there were 316 transfers performed in normal weight patients, 165 in overweight patients, and 81 in obese weight patients. There was no statistically significant difference in LBR across all BMI categories (55.4

PurposeTo investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET).MethodsOur retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5 mg of daily letrozole for 5 days starting on cycle day 2 or 3. Outcomes were compared using absolute standardized differences (ASD), in which a larger ASD signifies a larger difference. Multivariable regression models adjusted for confounders: maternal age, BMI, nulliparity, embryo grade, race, infertility diagnosis, and endometrial thickness.ResultsThe demographic and clinical characteristics were overall similar. A greater proportion of the letrozole cohort was multiparous, transferred high-graded embryos, and had ovulatory dysfunction. The cohorts had similar pregnancy rates (67.1% LTZ vs 62.1% NC; aOR 1.31, P = 0.21) and live birth rates (60.9% LTZ vs 58.6% NC; aOR 1.17, P = 0.46). LTZ-FET neonates on average were born 5.7 days earlier (P < 0.001) and had higher prevalence of prematurity (18.6% vs. 8.0%NC, ASD = 0.32) and low birth weight (10.4% vs. 5.0%, ASD = 0.20). Both cohorts' median gestational ages (38 weeks and 1 day for LTZ; 39 weeks and 0 day for NC) were full term.ConclusionThere were similar rates of pregnancy and live birth between LTZ-FET and NC-FET cycles. However, there was a higher prevalence of prematurity and low birth weight among LTZ-FET neonates. Reassuringly, the median gestational age in both cohorts was full term, and while the difference in gestational length of almost 6 days does not appear to be clinically significant, this warrants larger studies.

PURPOSE:To evaluate the cost-effectiveness of in-vitro fertilization with preimplantation genetic testing for aneuploidy and monogenic disorders (IVF with PGT-M/A) to prevent transmission of spinal muscular atrophy to offspring of carrier couples.METHODS:A decision-analytic model was created to compare the cost-effectiveness of IVF with PGT-M/A to unassisted conception with prenatal diagnostic testing and termination (if applicable). IVF with PGT-M/A costs were determined using a separate Markov state-transition model. IVF outcomes data was derived from 76 carriers of monogenic disorders who underwent IVF with PGT-M/A at a single academic REI center. Other probabilities, costs, and utilities were derived from the literature. Costs were modeled from healthcare perspective. Utilities were modeled from the parental perspective as quality-adjusted life-years (QALYs).RESULTS:The incremental cost-effectiveness ratio for IVF with PGT-M/A compared to unassisted conception is $22,050 per quality-adjusted life-year. The average cost of IVF with PGT-M/A is $41,002 (SD: $8,355). At willingness-to-pay thresholds of $50,000 and $100,000, IVF with PGT-M/A is cost-effective 93.3% and 99.5% of the time, respectively.CONCLUSIONS:Compared to unassisted conception, IVF with PGT-M/A is cost-effective for preventing the transmission of spinal muscular atrophy to the offspring of carrier couples. These findings support insurance coverage of IVF with PGT-M/A for carriers of spinal muscular atrophy.

We conducted a cost analysis of clomiphene citrate (CC) versus letrozole (LTZ) versus gonadotropin (GN) with intrauterine insemination (IUI) for couples with unexplained infertility. Using pregnancy outcomes data from the AMIGOS trial, cost data from publicly available sources, and taking into account associated maternal and neonatal care and complications associated with singleton, twin (TIUP), and higher order multiple (HOM) gestations, the study assessed the relative costs of each strategy.

The ideal placement of the embryo within the uterine cavity remains unclear according to the 2017 ASRM practice guideline for performing embryo transfers1,2. As summarized in this systematic review, prior data have shown mixed results ranging from no impact of location to higher success with catheter tip placement in the upper or middle portion of the uterus. Additionally, few studies looked at live birth rate as the primary outcome of interest and many studies involved untested embryos, mixed fresh/primarily medicated frozen cycles.

This study aims to compare endometrial growth before and after the addition of human growth hormone (hGH) in controlled ovarian hyperstimulation (COH) cycles. A 5-year retrospective cohort study of patients treated with hGH to improve oocyte development during COH cycles was conducted. Each patient’s cycle without hGH immediately preceding cycle(s) with hGH was used for patients to serve as their own controls. Primary outcome was absolute growth in endometrial thickness from pre-stimulation start to day of hCG trigger. Mixed-model regression analysis controlled for patient correlation over repeat cycles and potential confounders. 80 patients were included. Mean age was 39.7 years; mean BMI was 23.8 kg/m2. Majority of patients were nulliparous, non-smoking, and White or Asian. Most common diagnosis was diminished ovarian reserve. Endometrial growth was compared between 159 COH cycles with hGH and 80 COH control cycles; mean increase was 4.5 mm and 3.9 mm, respectively-an unadjusted difference of 0.6 mm (95% CI: 0.2–1.1, p = 0.01). After adjusting for demographic/clinical factors, hGH was associated with 0.9 mm greater endometrial growth (0.4–1.4, p < 0.01). Absolute increase in endometrial thickness was higher in COH cycles that included hGH. Further prospective studies in embryo transfer cycles are needed.

To evaluate whether morphology impacts the pregnancy and neonatal outcomes of euploid blastocysts, and whether maternal age still affects outcomes when top-graded, euploid blastocysts are used. This retrospective cohort study included all natural-cycle frozen embryo transfers (NC-FET) using an autologous, euploid blastocyst from June 2016 to June 2020 (n = 610). There were five groups based on embryo grade: AA, AB, BA, BB, and “any C”. For analysis of only AA-graded embryos, there were three maternal age groups: < 35, 35–39, and 40 + years. The main outcomes measured were clinical pregnancy and live birth rates, while the secondary outcomes included neonatal outcomes such as gestational age at delivery and birthweight. Multivariable logistic regression models were performed to adjust for confounders. Euploid blastocysts with poorer morphology had lower odds of pregnancy and live birth; specifically, embryos with inner cell mass (ICM) graded as “C” had statistically significant decreased odds of pregnancy (aOR 0.33, p = 0.04) and live birth (aOR 0.32, p = 0.03) compared with ICM grade “A”. The differences in pregnancy rate between trophectoderm grades were not statistically significant. Even in cycles that transferred a top-graded (AA) euploid embryo, maternal age at transfer was independently associated with outcomes. Embryo grade and maternal age, however, did not significantly impact neonatal outcomes such as prematurity and birthweight. The morphology of euploid blastocysts and maternal age at NC-FET both independently impact pregnancy outcomes. Neonatal outcomes were similar across embryo morphology and maternal age groups, suggesting that lower morphology euploid embryos not be discounted as viable options for transfer.

Objective: To assess the impact of withholding doxycycline on the success rate of natural cycle frozen embryo transfers (NC-FET). Design: Retrospective cohort study. Setting: Single academic institution. Patient(s): Women undergoing 250 NC-FET with euploid blastocysts performed by a single provider. Intervention(s): One hundred and twenty-five NC-FET cycles performed after January 2019 without antibiotic administration compared with 125 NC-FET cycles before January 2019 with doxycycline administration. Main Outcome Measure(s): Primary outcome: live birth (LB) or ongoing pregnancy rate (OPR, defined as pregnancies R13 weeks); secondary outcomes included positive b-human chorionic gonadotropin (b-hCG) level and clinical pregnancy rate (CPR, defined as the presence of fetal cardiac activity on ultrasound). Result(s): Each group of women comprised 125 NC-FET during the study period of March 2017 to March 2020. The women?s mean age was 36.3 years and mean body mass index was 24 kg/m2. Between the two groups, the baseline characteristics were similar, including age, body mass index, race, smoking status, parity, endometrial thickness, Society of Assisted Reproductive Technology diagnosis, and number of prior failed transfers. Comparing NC-FET with doxycycline administration versus without, we found no statistically significant difference in LB-OPR (64% vs. 62.6%), positive b-hCG (72.8% vs. 74.0%), or CPR (68% vs. 65.9%). After controlling for all variables in a logistic regression, doxycycline still had no effect on LB-OPR. Conclusion(s): In this analysis of similar patients undergoing NC-FET by a single provider, withholding doxycycline does not reduce success rates. Given the risks of antibiotics, our findings support withholding their use in NC-FET. (Fertil Sterile 2021;115:1225?31. ?2020 by American Society for Reproductive Medicine.) El resumen est? disponible en Espa?ol al final del art?culo.

To compare the predicted success and cost of achieving a live birth with IVF using donor oocytes from frozen egg banks versus fresh controlled ovarian hyperstimulation (COH) cycles. We constructed a decision analytic model to compare the predicted outcomes and costs of IVF using donor oocytes from frozen egg banks (up to two batches) versus one fresh COH cycle. It was assumed that one batch from a frozen egg bank contains 6-8 donor oocytes, and IVF results in at least 2 blastocysts; one fresh donor COH/IVF cycle results in at least 3 blastocysts; no preimplantation genetic testing is performed; successive single frozen-thawed embryo transfers occur until live birth is achieved or no blastocysts remain. Table 1 lists the key model inputs with their sources. We entered a theoretical cohort of 1,000 patients into the model to assess the average chance and cost of achieving a live birth with each treatment arm. Deterministic model calculations predicted the average chance of live birth after donor oocyte IVF is 68.2% when using up to two batches from a frozen egg bank ($53,902 average cost) versus 81.9% when using one fresh COH cycle ($62,481 average cost). REI providers face uncertainty when counseling patients to proceed with donor oocytes from egg banks versus fresh COH cycles. In our decision model, donor oocyte IVF using up to two batches from a frozen egg bank was successful and $8,579 less expensive than one fresh COH cycle, but also was predicted to have a relatively lower chance of live birth/surplus embryos. Willingness to pay for higher success and the desire for genetic siblings will likely influence choice of technique.