Mare and stallion effects on blastocyst production in a commercial equine ovum pick-up-intracytoplasmic sperm injection program.

This study retrospectively examined the degree to which success within a commercial ovum pick-up (OPU)-intracytoplasmic sperm injection (ICSI) program varied between individual mares and stallions. Over 2 years, 552 OPU sessions were performed on 323 privately owned warmblood mares. For mares that yielded at least one blastocyst during the first OPU-ICSI cycle, there was a 77% likelihood of success during subsequent attempts; conversely, when the first cycle yielded no blastocyst, the likelihood of failure (no embryo) in subsequent cycles was 62%. In mares subjected to four or more OPU sessions, the mean percentage of blastocysts per injected oocyte was 20.5% (range 1.4-46.7%), whereas the mean number of blastocysts per OPU-ICSI session was 1.67 (0.2-4.2). Age did not differ significantly between mares that yielded good or poor results. The number of recovered oocytes per OPU was positively associated with the likelihood of success (P<0.001). Although there were considerable between-stallion differences, most stallions (14/16) clustered between 15.6% and 26.8% blastocysts per injected oocyte, and the number of blastocysts per OPU (mean 1.4; range 0.2-2.2) was less variable than among mares. In conclusion, although both mare and stallion affect the success of OPU-ICSI, mare identity and the number of oocytes recovered appear to be the most reliable predictors of success.

Comparative evaluation of the cost and efficiency of four types of sexing methods for the production of dairy female calves.

This study was conducted to evaluate and compare the economic benefits of different embryo sexing methods, based on the cost per female dairy calf produced. Female calves were produced from four kinds of female embryos: (1) those collected from superstimulated donors at 7-8 days after artificial insemination (AI) with X-sorted semen; (2) those sex-determined by loop-mediated isothermal amplification assay of a biopsy sample of embryos collected from superstimulated donors after AI with conventional unsorted semen; (3) those obtained by invitro embryo production (IVEP), using X-sorted semen and in vitro-matured oocytes collected from donors by ovum pick-up (OPU); and (4) those obtained by IVEP, using X-sorted semen and oocytes collected by OPU after dominant follicle ablation and follicle growth stimulation of the donors. The respective productivities of female calves per technical service and the total production cost per female calf of each sexing method were compared. The production cost per female calf (66,537 JPY), as calculated from the number of female calves per service (1.30), pregnancy rate of transfer (42.9%), rate of female calves obtained (92.9%), and total cost of the method (56,643 JPY plus embryo transfer fee), was less for IVEP with X-sorted semen and follicular growth-stimulated (FGS) oocytes than for the other groups (P < 0.05). The results demonstrate that embryo production with X-sorted semen and FGS oocytes provides a more efficient method for producing female calves than the other embryo sexing methods.

[In vitro fertilization versus conversion to intrauterine insemination in patients with poor response to controlled ovarian hyperstimulation]. / Réponse insuffisante à la stimulation en vue de FIV : maintenir la ponction ou choisir l' insémination ?

In women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF), a poor ovarian response, defined as three of fewer mature follicles, can lead to cancellation of the cycle. However, in women with at least one patent tube and normal semen parameters, conversion to intrauterine insemination (IUI) is considered an option, offering reasonable pregnancy rates at a lower cost and without the complications associated with oocyte retrieval. Studies have shown that in cycles with only one mature follicle, IVF should be canceled. However, in cycles with 2 or 3 mature follicles, patients have the choice between IVF and conversion to IUI. Some studies have shown that IVF is superior to IUI in such cases, whereas other reports failed to find any difference. Most of these studies are retrospective and limited by the presence of several biases and low numbers of cycles, and to this date, there is no consensus on the best approach. We have thus designed a multicenter, randomized non-inferiority study, comparing live birth rates following conversion to IUI or IVF in patients with 2 or 3 mature follicles in COH cycles. Nine hundred and forty patients will be randomized on trigger day to either IVF or conversion to IUI. Our study will also include a medico-economic analysis.

Fertility Preservation in Breast Cancer.

As more young women survive breast cancer, fertility preservation (FP) is an important component of care. This review highlights the importance of early pretreatment referral, reviews the risks of infertility associated with breast cancer treatment, and defines existing and emerging techniques for FP. The techniques reviewed include ovarian suppression, embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation and transplantation. The barriers women face, such as not being appropriately referred and the costs of treatment, also are addressed. Multidisciplinary, patient-centered care is essential to discussing FP with patients with breast cancer and ensuring appropriate care that includes quality of life in survivorship.

Comparison of costs associated with substituting culture medium with saline solution for follicular flushing during oocyte retrieval.

OBJECTIVES: To compare culture medium and saline solution for follicular flushing during oocyte retrieval with assisted reproductive technologies. METHODS: The present retrospective study analyzed data collected at Galway Fertility Clinic, Galway, Ireland, between January 1, 2015 and August 31, 2016; all patients attending the clinic for in vitro fertilization/intracytoplasmic sperm injection during this period were included. Data were stratified by whether follicular flushing was performed with culture medium or saline, and the oocyte yield rate, fertilization rate, embryo utilization rate, and biochemical and clinical pregnancy rates were compared between the groups. RESULTS: In total, 422 oocyte retrieval procedures with culture medium and 277 with normal saline were analyzed. The fertilization (P=0.676) and clinical pregnancy rates (P=0.593) did not differ between the groups. Using normal saline resulted in an approximately 41-fold per-patient cost saving compared with culture medium. CONCLUSION: Switching from culture medium to normal saline for follicular flushing significantly reduced oocyte-retrieval costs without adversely affecting reproductive outcomes.

Assessing reproductive choices of women and the likelihood of oocyte cryopreservation in the era of elective oocyte freezing.

OBJECTIVE: To assess reproductive choices of reproductive-age women in the United States and factors that influence consideration of elective egg freezing (EF). DESIGN: Cross-sectional internet-based survey. SETTING: Not applicable. PATIENTS: One thousand women aged 21-45 years. INTERVENTION(S): An anonymous 63-item self-administered questionnaire was distributed to a representative cross-section of women aged 21-45 years, stratified by age <35 years. One-half of the sample had at least one child, and the other one-half did not. All of the participants were interested in having children. MAIN OUTCOME MEASURE(S): Ordinal logistic regression was performed to characterize the association of population characteristics and reproductive knowledge with likelihood to consider EF. Willingness to pay was assessed with the use of a linear prediction model that calculated dollar amounts at varying success rates. RESULT(S): Overall, 87.2% of the sample reported awareness of EF for fertility preservation and 25% would consider this option, yet only 29.8% knew what the EF process entails. Once informed of the process, 30% of women changed their level of consideration. In a multivariable model, Asian race, single status, and infertility increased the likelihood of considering EF. Women likely to consider egg freezing would be willing to pay $3,811.55 (95% confidence interval $2,862.66-$4,760.44). If the total cost were $10,000, 91% of the cohort would accept at minimum a 50% chance of successful delivery. CONCLUSION(S): This study is one of the largest cohorts of reproductive-age women in the United States addressing reproductive choices and factors associated with the importance of having a biologically related child and the likelihood of considering EF to preserve fertility. This study provides important insight into the willingness to pay for this elective endeavor.

Financial compensation of oocyte donors: an Ethics Committee opinion.

Financial compensation of women donating oocytes for infertility therapy or for research is justified on ethical grounds and should acknowledge the time, inconvenience, and discomfort associated with screening, ovarian stimulation, and oocyte retrieval, and not vary according to the planned use of the oocytes, the number or quality of oocytes retrieved, the number or outcome of prior donation cycles, or the donor's ethnic or other personal characteristics. This document replaces the document of the same name, last published in 2007 (Fertil Steril 2007;88:305-9).

Optimal timing for elective egg freezing.

OBJECTIVE: To estimate the optimal age to pursue elective oocyte cryopreservation. DESIGN: A decision-tree model was constructed to determine the success and cost-effectiveness of oocyte preservation versus no action when considered at ages 25-40 years, assuming an attempt at procreation 3, 5, or 7 years after initial decision. SETTING: Not applicable. PATIENT(S): Hypothetical patients 25-40 years old presenting to discuss elective oocyte cryopreservation. INTERVENTION(S): Decision to cryopreserve oocytes from age 25 years to age 40 years versus taking no action. MAIN OUTCOME AND MEASURE(S): Probability of live birth after initial decision whether or not to cryopreserve oocytes. RESULT(S): Oocyte cryopreservation provided the greatest improvement in probability of live birth compared with no action (51.6% vs. 21.9%) when performed at age 37 years. The highest probability of live birth was seen when oocyte cryopreservation was performed at ages <34 years (>74%), although little benefit over no action was seen at ages 25-30 years (2.6%-7.1% increase). Oocyte cryopreservation was most cost-effective at age 37 years, at $28,759 per each additional live birth in the oocyte cryopreservation group. When the probability of marriage was included, oocyte cryopreservation resulted in little improvement in live birth rates. CONCLUSION(S): Oocyte cryopreservation can be of great benefit to specific women and has the highest chance of success when performed at an earlier age. At age 37 years, oocyte cryopreservation has the largest benefit over no action and is most cost-effective.

Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth.

OBJECTIVE: To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice. DESIGN: Decision-tree mathematical model with sensitivity analyses. SETTING: Not applicable. PATIENT(S): A simulated cohort of women wishing to delay childbearing until age 40 years. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cost per live birth. RESULT(S): Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from $55,060 to $39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to $61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes. CONCLUSION(S): In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth.

Cost-effectiveness analysis comparing continuation of assisted reproductive technology with conversion to intrauterine insemination in patients with low follicle numbers.

OBJECTIVE: To compare the cost effectiveness of proceeding with oocyte retrieval vs. converting to intrauterine insemination (IUI) in patients with ≤4 mature follicles during assisted reproductive technology (ART) cycles. DESIGN: Probabilistic decision analysis. The cost effectiveness of completing ART cycles in poor responders was compared to that for converting the cycles to IUI. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Cost-effectiveness analysis. MAIN OUTCOME MEASURE(S): Cost effectiveness, which was defined as the average direct medical costs per ongoing pregnancy. RESULT(S): In patients with 1-3 mature follicles, completing ART was more cost effective if the cost of a single ART cycle was between $10,000 and $25,000. For patients with 4 mature follicles, if an ART cycle cost<$18,025, it was more cost effective to continue with oocyte retrieval than to convert to IUI. CONCLUSION(S): In patients with ≤4 mature follicles following ovarian stimulation in ART cycles, it was on average more cost effective to proceed with oocyte retrieval rather than convert to IUI. However, important factors, such as age, prior ART failures, other fertility factors, and medications used in each individual case need to be considered before this analysis model can be adapted by individual practices.

Modified natural cycle versus controlled ovarian hyperstimulation IVF: a cost-effectiveness evaluation of three simulated treatment scenarios.

STUDY QUESTION: Can modified natural cycle IVF or ICSI (MNC) be a cost-effective alternative for controlled ovarian hyperstimulation IVF or ICSI (COH)? SUMMARY ANSWER: The comparison of simulated scenarios indicates that a strategy of three to six cycles of MNC with minimized medication is a cost-effective alternative for one cycle of COH with strict application of single embryo transfer (SET). WHAT IS KNOWN ALREADY: MNC is cheaper per cycle than COH but also less effective in terms of live birth rate (LBR). However, strict application of SET in COH cycles reduces effectiveness and up to three MNC cycles can be performed at the same costs as one COH cycle. STUDY DESIGN, SIZE, DURATION: The cost-effectiveness of MNC versus COH was evaluated in three simulated treatment scenarios: three cycles of MNC versus one cycle of COH with SET or double embryo transfer (DET) and subsequent transfer of cryopreserved embryos (Scenario 1); six cycles of MNC versus one cycle of COH with strictly SET and subsequent transfer of cryopreserved embryos (Scenario 2); six cycles of MNC with minimized medication (hCG ovulation trigger only) versus one cycle of COH with SET or DET and subsequent transfer of cryopreserved embryos (Scenario 3). We used baseline data obtained from two retrospective cohorts of consecutive patients (2005-2008) undergoing MNC in the University Medical Center Groningen (n = 499, maximum six cycles per patient) or their first COH cycle with subsequent transfer of cryopreserved embryos in the Academic Medical Center Amsterdam (n = 392). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 1994 MNC cycles (958 MNC-IVF and 1036 MNC-ICSI) and 392 fresh COH cycles (one per patient, 196 COH-IVF and 196 COH-ICSI) with subsequent transfer of cryopreserved embryos (n = 72 and n = 94 in MNC and COH cycles, respectively) in ovulatory, subfertile women <36 years of age served as baseline for the three simulated scenarios. To compare the scenarios, the incremental cost-effectiveness ratio (ICER) was calculated, defined as the ratio of the difference in IVF costs up to 6 weeks postpartum to the difference in LBR. Live birth was the primary outcome measure and was defined as the birth of at least one living child after a gestation of ≥25 weeks. MAIN RESULTS AND THE ROLE OF CHANCE: In the baseline data, MNC was not cost-effective, as COH dominated MNC with a higher cumulative LBR (27.0 versus 24.0%) and lower cost per patient (€3694 versus €5254). The simulations showed that in scenario 1 three instead of six cycles lowered the costs of MNC to below the level of COH (€3390 versus €3694, respectively), but also lowered the LBR per patient (from 24.0 to 16.2%, respectively); Scenario 2: COH with strict SET was less effective than six cycles MNC (LBR 17.5 versus 24.0%, respectively), but also less expensive per patient (€2908) than MNC (€5254); Scenario 3: improved the cost-effectiveness of MNC but COH still dominated MNC when medication was minimized in terms of costs, i.e. €855 difference in favor of COH and 3% difference in LBR in favor of COH (ICER: €855/-3.0%). LIMITATIONS, REASONS FOR CAUTION: Owing to the retrospective nature of the study, the analyses required some assumptions, for example regarding the costs of pregnancy and delivery, which had to be based on the literature rather than on individual data. Furthermore, costs of IVF treatment were based on tariffs and not on actual costs. Although this may limit the external generalizability of the results, the limitations will influence both treatments equally, and would therefore not bias the comparison of MNC versus COH. WIDER IMPLICATIONS OF THE FINDINGS: The combined results suggest that MNC with minimized medication might be a cost-effective alternative for COH with strict SET. The scenarios reflect realistic alternatives for daily clinical practice. A preference for MNC depends on the willingness to trade off effectiveness in terms of LBR against the benefits of a milder stimulation regimen, including a very low rate of multiple pregnancies and hyperstimulation syndrome and ensuing lower costs per live birth. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by research grants from Merck Serono and Ferring Pharmaceuticals. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

The sharing of eggs by infertile women who are trying to conceive themselves with an egg recipient for financial advantages does not jeopardize the donor's chance of conceiving.

PURPOSE: To determine if the sharing of oocytes by an infertile woman with an egg recipient for financial advantages has any negative impact on the success rate for the donor. METHODS: A matched controlled study was performed comparing pregnancy outcome of women undergoing in vitro fertilization-embryo transfer (IVF-ET) but sharing half of their eggs with a recipient vs women undergoing IVF-ET but not sharing oocytes. RESULTS: Even though more women sharing oocytes deferred fresh transfer and cryopreserved the embryos because of a greater likelihood of ovarian hyperstimulation syndrome, there was no difference in pregnancy rates between the two groups after their first embryo transfer whether it was with fresh or frozen-thawed embryos. CONCLUSIONS: Sharing of oocytes by a woman undergoing IVF-ET does not jeopardize her chance of a successful outcome following embryo transfer.

Discordant views of experts and laypersons on the adoption of new fertility technology.

BACKGROUND: Healthcare costs are increased by the adoption of novel technologies before solid evidence on efficacy and risks. Oocyte cryopreservation for preserving fertility raises special ethical challenges. We compared opinions of professionals for assisted reproductive technology (ART), bioethicists, medical students and the general population toward the questions: do you support access to oocyte cryopreservation to preserve fertility for personal reasons and who should bear the costs? METHODS: The surveys conducted for this study were carried out in Israel included the following: (1) survey of 21 ART unit directors; (2) interviews with 23 bioethics experts; (3) survey of 196 medical students from 2 universities; (4) random digit-dial population-based survey of the public (N=600). RESULTS: Nearly 80% of ART and bioethics experts and 56% of students thought that oocyte cryopreservation should be allowed even for personal reasons. While expressing concerns about social consequences, bioethicists emphasized individuals' rights. In contrast, among the public, only 40% supported the use of this technology for personal reasons (ranging from 24% among Ultra-orthodox Jews and Arabs, to 51% among seculars or with academic education). Of note, 15% were undecided (vs. <2% among students, P<0.001). Most experts suggested private financing of the procedure for personal reasons, whereas the public preferred national or private insurance coverage. CONCLUSIONS: Nonexperts present a greater level of ambivalence than experts toward the use of a novel fertility technology for nonmedical reasons. Experts' preferences and interests may facilitate adoption of novel technologies with yet unclear effectiveness and safety, potentially contributing to increased healthcare costs.

Assisted reproduction in women over 40 years of age: how old is too old?

Women's fertility progressively declines with advanced age due to depletion of the ovarian follicular reserve and poorer oocyte quality. However, many women of advanced age are eager to conceive from their own ova. The aim of the present study was to evaluate the outcome of IVF cycles among older patients. All IVF retrievals performed in the unit in patients >or=42 years old between 1998 and 2006 were retrospectively analysed. Data were compared with patients <35 years old treated in the unit during the same time period. A total of 843 IVF retrievals in 459 patients >or=42 years old were assessed. Clinical pregnancy rates per cycle were 7.7%, 5.4% and 1.9% for 42, 43 and 44 years old, respectively. Only one IVF cycle in patients aged 44 years resulted in delivery. None of the 54 cycles performed in women of 45 years or older resulted in a pregnancy. A marked decline in clinical pregnancy and delivery rates, accompanied by an increase in spontaneous abortion rates, was found in patients >or=42 years old. In view of these results and as the option of egg donation is a promising alternative with delivery rates close to 50%, it appears that IVF treatment should be limited to patients not older than 43 years old with adequate ovarian response.

A detailed cost analysis of in vitro fertilization and intracytoplasmic sperm injection treatment.

OBJECTIVE: To provide detailed information about costs of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment stages and to estimate the cost per IVF and ICSI treatment cycle and ongoing pregnancy. DESIGN: Descriptive micro-costing study. SETTING: Four Dutch IVF centers. PATIENT(S): Women undergoing their first treatment cycle with IVF or ICSI. INTERVENTION(S): IVF or ICSI. MAIN OUTCOME MEASURE(S): Costs per treatment stage, per cycle started, and for ongoing pregnancy. RESULT(S): Average costs of IVF and ICSI hormonal stimulation were euro 1630 and euro 1585; the costs of oocyte retrieval were euro 500 and euro 725, respectively. The cost of embryo transfer was euro 185. Costs per IVF and ICSI cycle started were euro 2381 and euro 2578, respectively. Costs per ongoing pregnancy were euro 10,482 and euro 10,036, respectively. CONCLUSION(S): Hormonal stimulation covered the main part of the costs per cycle (on average 68% and 61% for IVF and ICSI, respectively) due to the relatively high cost of medication. The costs of medication increased with increasing age of the women, irrespective of the type of treatment (IVF or ICSI). Fertilization costs (IVF laboratory) constituted 12% and 20% of the total costs of IVF and ICSI. The total cost per ICSI cycle was 8.3% higher than IVF.