Remote IVF: a clinical and laboratory guide to performing remote oocyte retrievals.

The aim of this guide is to describe different scenarios when remote IVF would be needed, considerations around how to plan for the procedure, proper equipment in the procedure room, and proper transportation of oocytes from the procedure room. There are two different scenarios for remote IVF: (1) IVF clinics designed knowing the embryology laboratory is nonadjacent and (2) IVF clinics that routinely provide care to patients in their clinic and want to provide care to those who are ineligible for a retrieval under anesthesia in an outpatient facility. This guide will focus on both scenarios. Much of the advice can be used for IVF clinics that routinely perform oocyte retrievals nonadjacent to their embryology laboratories. Special considerations are needed when patients with complex comorbidities require high-level of care and hospital-level monitoring while under anesthesia and/or post-oocyte retrieval, and are thus unable to be treated in the standard facility. For these reasons we have created a comprehensive guide to nonadjacent, or off-site, oocyte retrievals for reproductive endocrinology and infertility (REI) physicians, nurses, and embryologists to use when planning care for IVF patients. Going forward, we will refer to both these scenarios as remote IVF.

The incidence of ectopic/heterotopic pregnancies after blastocyst-stage frozen-thawed embryo transfers compared with that after cleavage-stage: a Society for Assisted Reproductive Technologies Clinical Outcomes Reporting System study.

OBJECTIVE: To investigate whether there is a difference in the ectopic/heterotopic pregnancy rate of blastocyst-stage frozen-thawed embryo transfers (FETs) compared with that of cleavage-stage FETs. DESIGN: A retrospective cohort study. SETTING: Not applicable. PATIENTS: Women undergoing autologous FETs at either the blastocyst stage (n = 118,572) or the cleavage stage (n = 117,619), as reported to the Society for Assisted Reproductive Technology from 2004 to 2013. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Pregnancy outcomes, specifically ectopic pregnancy rates and heterotopic pregnancy rates. RESULTS: Among those who became pregnant, there was a significantly lower incidence of ectopic/heterotopic pregnancies in blastocyst-stage FETs versus that in cleavage-stage FETs (0.8% vs. 1.1%). The differences in ectopic/heterotopic pregnancy rates remained statistically significant after controlling for confounders such as tubal factor infertility and number of embryos transferred. CONCLUSIONS: Blastocyst-stage FET was associated with a lower ectopic/heterotopic pregnancy rate compared with cleavage-stage FET.

Increased male live-birth rates after blastocyst-stage frozen-thawed embryo transfers compared with cleavage-stage frozen-thawed embryo transfers: a SART registry study.

OBJECTIVE: To investigate whether there is a difference in live-birth gender rates in blastocyst-stage frozen-thawed embryo transfers (FETs) compared with those in cleavage-stage FETs. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: All women with recorded live births who underwent FET at either the blastocyst or cleavage stage, reported to the Society for Assisted Reproductive Technology during 2004-2013. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was live-birth gender rates. Demographic criteria were also collected. The chi-square analyses were used for bivariate associations, and multiple logistic regression models were used for adjusted associations, with all two-sided P<.05 considered statistically significant. RESULTS: A statistically significant increase was noted in the number of live male births after blastocyst-stage FET compared with that after cleavage-stage FET (51.9% vs. 50.5%). After controlling for potential confounders including age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.03, 1.08), body mass index (OR, 1.08; 95% CI, 1.04, 1.12), and male factor infertility (OR, 1.06; 95% CI, 1.03, 1.08), the increase in male live births after blastocyst-stage FET remained statistically significant. CONCLUSIONS: In patients undergoing FETs, blastocyst-stage transfers are associated with higher male gender live-birth rates compared with cleavage-stage transfers.

Improved outcomes after blastocyst-stage frozen-thawed embryo transfers compared with cleavage stage: a Society for Assisted Reproductive Technologies Clinical Outcomes Reporting System study.

OBJECTIVE: To investigate whether there is a difference in obstetrical and perinatal outcomes in blastocyst frozen-thawed embryo transfers (FETs) compared with cleavage-stage FET. DESIGN: A retrospective cohort study. SETTING: Not applicable. PATIENT(S): Women undergoing autologous FETs at either the blastocyst stage (n = 118,572) or the cleavage stage (n = 117,619) reported to the Society for Assisted Reproductive Technology in the years 2004-2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth, gestational age, birth weight, miscarriage. RESULT(S): After controlling for confounders, there were a 49% increased odds of live birth after blastocyst-stage FET compared with cleavage-stage FET (odds ratio [OR] = 1.49; 95% confidence interval [CI], 1.44, 1.54). Additionally, blastocyst FET was associated with a 68% (OR = 1.68; 95% CI, 1.63, 1.74) increased odds of clinical pregnancy and an 7% (OR = 0.93; 95% CI, 0.88, 0.92) decreased odds of miscarriage. There was also a 16% increased odds of preterm delivery (OR = 1.16; 95% CI, 1.06, 1.27) after blastocyst FET but no difference in birth weights. CONCLUSION(S): In patients undergoing FET, blastocyst-stage transfer is associated with higher live-birth rates when compared with cleavage-stage transfers. Furthermore, perinatal outcomes are similar between the groups.

Serum and follicular fluid monocyte chemotactic protein-1 levels are elevated in obese women and are associated with poorer clinical pregnancy rate after in vitro fertilization: a pilot study.

OBJECTIVE: To determine whether monocyte chemotactic protein-1 (MCP-1), a proinflammatory chemokine important in ovulation, is abnormally elevated in obese women undergoing IVF and whether serum and follicular fluid (FF) levels of MCP-1 are associated with IVF outcome. DESIGN: Prospective pilot study. SETTING: Academic center. PATIENT(S): Women undergoing IVF. INTERVENTION(S): Serum and FF were collected from women undergoing IVF. MAIN OUTCOME MEASURE(S): Correlation between MCP-1 and other inflammatory markers with adiposity and pregnancy outcome after IVF. RESULT(S): Obese women had significantly higher serum and FF MCP-1 levels compared with overweight and normal weight women. Serum MCP-1, granulocyte colony stimulating factor, catalase, and C-reactive protein (CRP) were positively correlated with body mass index (BMI). After adjusting for age and baseline FSH, these correlations remained significant for serum MCP-1, granulocyte colony stimulating factor, and CRP. In the FF, only MCP-1 was positively correlated with BMI. Women who became pregnant had significantly lower serum MCP-1 and CRP levels compared with those who did not become pregnant; this difference was more pronounced among women with diminished ovarian reserve. Receiver operating characteristic curve demonstrated that serum MCP-1 levels >373.0 pg/mL in all women and >362.6pg/mL in women with diminished ovarian reserve predicted failure to achieve a clinical pregnancy. CONCLUSION(S): Elevations in serum and FF MCP-1 levels are positively correlated with adiposity and negatively correlated with pregnancy rates (PRs) in women undergoing IVF.

Guidelines for risk reduction when handling gametes from infectious patients seeking assisted reproductive technologies.

According to the Americans with Disabilities Act (1990), couples with blood-borne viruses that lead to infectious disease cannot be denied fertility treatment as long as the direct threat to the health and safety of others can be reduced or eliminated by a modification of policies or procedures. Three types of infectious patients are commonly discussed in the context of fertility treatment: those with human immunodeficiency virus (HIV), hepatitis C or hepatitis B. Seventy-five per cent of hepatitis C or HIV positive men and women are in their reproductive years, and these couples look to assisted reproductive techniques for risk reduction in conceiving a pregnancy. In many cases, only one partner is infected. Legal and ethical questions about treatment of infectious patients aside, the question most asked by clinical embryologists and andrologists is: "What are the laboratory protocols for working with gametes and embryos from patients with infectious disease?" The serostatus of each patient is the key that informs appropriate treatments. This guidance document describes protocols for handling gametes from seroconcordant and serodiscordant couples with infectious disease. With minor modifications, infectious patients with stable disease status and undetectable or low viral load can be accommodated in the IVF laboratory.

Reporting in vitro fertilization cycles to the Society for Assisted Reproductive Technology database: where have all the cycles gone?

OBJECTIVE: To assess the relationship between live birth rates (LBRs) and the incidence of under-reported cycles by IVF clinics. DESIGN: Cohort study. SETTING: Not applicable. PATIENT(S): All patients undergoing IVF cycles in the aforementioned clinics. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The reporting percentage (RP), defined as number of cycles with reported pregnancy rates divided by total cycles performed. Results from cryopreservation cycles are only presented by SART if an embryo transfer occurs. Thus, RP decreases as incidence of embryo or oocyte banking cycles increases. The LBRs in women aged <35 years were compared between clinics. RESULT(S): The median RP of all clinics was 93%-97%. Clinics with RP <80% increased from 2 in 2004 to 30 in 2012. Twenty-one clinics had an RP that fell 2 standard deviations below the mean in any year. Over the 9 years, there was a negative correlation between RP and LBR of -0.17, but for the 21 outlier clinics the correlation increased to -0.26. In 2012 alone, in outlier clinics, for every 10% drop in RP there was an associated rise in LBR of 4.3%; some clinics reported 40% fewer cycles than the median. CONCLUSION(S): In clinics with very low RP, the cycles that are reported have higher success rates. Regardless of intent, the reduction of reported data to SART makes it increasingly difficult for clinicians and patients to accurately assess a clinic's success rates.

Blood type predicts live birth in the infertile population.

PURPOSE: To determine if blood type in infertile women relates to the likelihood for live birth (LB) following IVF, and to the etiology for infertility. METHODS: Retrospective study of patients undergoing IVF at two academic centers in the northeast US. Relationships between blood type (A, B, AB, O) and patient characteristics, IVF cycle parameters and LB were assessed utilizing multivariable logistic regression analyses. RESULTS: In the studied population (n=626), women with type O were significantly more likely to have baseline FSH > 10 IU/L after adjusting for age, BMI and race (OR 5.09, 95 % CI 1.4-18.7, p=0.01). Conversely, women with blood type A were significantly more likely to have ovulatory infertility compared to those with blood type O after adjusting for age and BMI (OR 3.2, 95 % CI 1.7-6.2). Blood type B was associated with increased likelihood of live birth (OR 1.9, 95 % CI 1.10-3.41, p=0.03) after adjusting for factors recognized to impact IVF outcome. CONCLUSION: Ovulatory infertility and baseline FSH > 10 IU/L were more prevalent in women with blood type A and O respectively. However, those of blood type B had significantly higher odds for LB compared to other blood types after adjusting for factors recognized to impact on IVF cycle outcome. While underlying mechanisms are unclear, for infertile women, patient's blood type is seemingly relevant for IVF cycle outcome.

Effect of single embryo transfer on the risk of preterm birth associated with in vitro fertilization.

PURPOSE: To determine whether elective single embryo transfer (eSET) reduces the risk of preterm delivery associated with in vitro fertilization (IVF). METHODS: This is an observational study of 3125 eSET cycles performed from 2008 to 2009 and reported to the Society for Assisted Reproductive Technology (SART) database. Preterm delivery rates were compared to the overall preterm delivery rate among all patients undergoing IVF over the same time period. RESULTS: The 3125 eSET cycles resulted in 1507 live births (live birth rate 48.2 %) Among these deliveries were 27 twins (1.8 %) and one set of triplets (0.07 %). The overall preterm delivery rate (20-37 weeks gestation) following eSET was 17.6 % (269/1527). This is significantly greater than the preterm birth rate for all patients undergoing IVF over the same time period (12 %, P < 0.001). CONCLUSIONS: Elective single embryo transfer does not reduce the risk of preterm delivery associated with in vitro fertilization (IVF).

Using the Society for Assisted Reproductive Technology Clinic Outcome System morphological measures to predict live birth after assisted reproductive technology.

OBJECTIVE: To model morphological assessments of embryo quality that are predictive of live birth. DESIGN: Longitudinal cohort using cycles reported in the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) between 2007 and 2011. SETTING: Clinic-based data. PATIENT(S): Fresh autologous assisted reproductive technology (ART) cycles with ETs on day 3 or day 5 and morphological assessments reported (25,409 cycles with one embryo transferred and 96,093 cycles with two embryos transferred). Live-birth rates were modeled by morphological assessments using backward-stepping logistic regression for cycle 1 and over five cycles, separately for day 3 and day 5 transfers and number of embryos transferred (1 or 2). Additional models for each day of transfer also included the number of oocytes retrieved and the number of embryos cryopreserved. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live births. RESULT(S): Morphological assessments of grade, stage, fragmentation, and symmetry were significant for the day 3 models; grade, stage, and trophectoderm were significant in the day 5 model; inner-cell mass was significant in the models when two embryos were transferred. Number of oocytes retrieved and number of embryos cryopreserved were significant for both day 3 and day 5 models. CONCLUSION(S): These findings confirm the significant association between embryo quality parameters reported to SART CORS and live-birth rate after ART.

Blastocyst expansion score and trophectoderm morphology strongly predict successful clinical pregnancy and live birth following elective single embryo blastocyst transfer (eSET): a national study.

PURPOSE: To determine which characteristics of blastocyst embryo morphology may predict clinical pregnancy and live birth rates. METHODS: A retrospective analysis of data from 3,151 cycles of fresh, non-donor eSET cycles from 2008 to 2009 was performed. Data were obtained from the Society for Assisted Reproductive Technologies (SART) underwent. All eSET were performed at the blastocyst stage. Main outcome measures were clinical pregnancy and live birth rates. RESULTS: Trophectoderm morphology, embryo stage and patient age are highly significant independent predictors of both clinical pregnancy and live birth. Neither inner cell mass morphology nor embryo grade predicted clinical pregnancy or live birth. CONCLUSIONS: Better trophectoderm morphology, younger patient age and further blastocyst progression all result in higher clinical pregnancy and live birth rates. Therefore, trophectoderm morphology and blastocyst stage should preferentially be used as the most important factors in choosing the best embryo for transfer.

Determining an anti-Mullerian hormone cutoff level to predict clinical pregnancy following in vitro fertilization in women with severely diminished ovarian reserve.

PURPOSE: Serum anti-Mullerian hormone (AMH) levels estimate ovarian reserve. The purpose of this study was to identify a minimum serum AMH level that correlates with acceptable clinical pregnancy rate (CPR) in women with severe diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF). METHODS(S): A historical cohort of severe DOR participants (age ≥35) with day 3 FSH of >10 ng/mL were included (n = 120). Participants were categorized into 3 groups: AMH <0.2 (Group 1, n = 38), AMH = 0.2-0.79 (Group 2, n = 57) and AMH ≥ 0.8 (Group 3, n = 25) ng/mL. The main outcome was CPR. The number of retrieved and mature oocytes, transferred embryos, spontaneous abortion (SAB) and live birth (LB) rates were also evaluated. RESULT(S): Among the three groups, there was no difference in day 3 FSH and estradiol, total gonadotropins dose used per cycle, or LB. Participants in Group 1 were two years older than those in Group 2 and had significantly higher BMI than those in Groups 2 and 3. The three groups significantly differed in AFC (Group 1< Group 2< Group 3; p = 0.001) and cycle cancellation rate (Group 1> Group 2> Group 3; p = 0.006), and had a trend toward significance in SAB rate (Group 1> Group 2> Group 3; p = 0.06). Group 3 had significantly more retrieved and mature oocytes than Groups 1 or 2. Group 2 and 3 had significantly higher CPR per cycle start compared to Group 1. Although Group 2 had significantly fewer oocytes retrieved and mature oocytes than Group 3, CPR per cycle start for both groups was not different. ROC curve indicated that the point of maximal inflection between lower and higher CPR represents an AMH value of 0.2 ng/mL. CONCLUSION(S): AMH of 0.2 ng/mL appears to be a meaningful threshold for predicting CPR in women with severe DOR at our practice. This information can be crucial during the pre-cycle counseling of these women.

Male adiposity impairs clinical pregnancy rate by in vitro fertilization without affecting day 3 embryo quality.

OBJECTIVE: Male adiposity is detrimental for achieving clinical pregnancy rate (CPR) following assisted reproductive technologies (ART). The hypothesis that the association of male adiposity with decreased success following ART is mediated by worse embryo quality was tested. DESIGN AND METHODS: Retrospective study including 344 infertile couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles was performed. Cycle determinants included number of oocytes retrieved, zygote PN-score, total number of embryos available on day 3, number of embryos transferred, composite day 3 grade for transferred embryos, composite day 3 grade per cycle, and CPR. RESULTS: Couples with male body mass index (BMI) over 25 kg m(-2) (overweight and obese) exhibited significantly lower CPR compared to their normal weight counterparts (46.7% vs. 32.0% respectively, P = 0.02). No significant difference was observed for any embryo quality metrics when analyzed by male BMI: mean zygote PN-scores, mean composite day 3 grades for transferred embryos or composite day 3 grades per cycle. In a multivariable logistic regression analysis adjusting for female age, female BMI, number of embryos transferred and sperm concentration, male BMI over 25 kg m(-2) was associated with a lower chance for CPR after IVF (OR = 0.17 [95% CI: 0.04-0.65]; P = 0.01) but not after ICSI cycles (OR = 0.88 [95% CI: 0.41-1.88]; P = 0.75). In this cohort, male adiposity was associated with decreased CPR following IVF but embryo quality was not affected. CONCLUSIONS: Embryo grading based on conventional morphologic criteria does not explain the poorer clinical pregnancy outcomes seen in couples with overweight or obese male partner.

How many eggs are needed to produce an assisted reproductive technology baby: is more always better?

OBJECTIVE: To evaluate the association between the number of mature (metaphase II [MII]) oocytes per assisted reproductive technology (ART) cycle and the likelihood of live birth. DESIGN: Retrospective study. SETTING: Academic infertility practice. PATIENT(S): Seven hundred thirty-seven infertile women undergoing their initial fresh embryo, nondonor IVF or intracytoplasmic sperm injection cycle at Montefiore's Institute for Reproductive Medicine and Health between January 2002 and December 2008. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Two hundred twenty-four cycles resulted in a live birth (30.4%). Live birth cycles had significantly more MII oocytes obtained per cycle as compared with their unsuccessful counterparts (11.0 ± 5.9 vs. 9.7 ± 6.2, respectively). Multivariate logistic regression was done to determine the minimum number of MII oocytes per cycle as a predictor of live birth after adjustment for age and historical maximum FSH values. Cycles that included the average number of MII in this cohort were used as a reference group. For cycles with five or fewer MII oocytes obtained, there was a statistically significant decrease in the likelihood of a live birth as compared with the reference group (odds ratio 0.61, 95% confidence interval 0.38-0.99). However, cycles with six or fewer obtained MII oocytes were not less likely to result in a live birth when compared with the reference group (odds ratio 0.69, 95% confidence interval 0.45-1.08). CONCLUSION(S): In our cohort, there was an advantage to obtaining six or more MII oocytes during the fresh oocyte retrieval compared with five or fewer oocytes. There was not an advantage, however, to obtaining 10 or more or 15 or more oocytes as compared with obtaining 6-9 oocytes. The strategy of aiming for a greater number of oocytes in an ART cycle should be revisited.

Full-sibling embryos created by anonymous gamete donation in unrelated recipients.

OBJECTIVE: To report the rare occurrence of full-sibling embryos in unrelated women using independently chosen donor sperm and donor oocytes in two different cycles unintentionally created at our IVF program, and to discuss the concept of disclosure to the patients. DESIGN: Case report. SETTING: Academic IVF program. PATIENT(S): Two women independently undergoing donor recipient cycles with anonymous donor oocytes and donor sperm. INTERVENTION(S): Both women received oocytes from the same donor several months apart and then by coincidence selected the same anonymous sperm donor to create anonymous full-sibling embryos. MAIN OUTCOME MEASURE(S): Clinical pregnancy after donor-recipient IVF cycle. RESULT(S): Both women conceived using the same donor sperm and donor oocytes in independent cycles, resulting in simultaneous pregnancy of full siblings. CONCLUSION(S): As providers with the knowledge that anonymous full sibling embryos have been created, we may have an obligation to disclose this information to the patients.

Prolonged gonadotropin stimulation is associated with decreased ART success.

PURPOSE: to evaluate whether the duration of gonadotropin stimulation predicts the likelihood of live birth after ART. METHODS: all IVF or ICSI cycles using fresh autologous oocytes at our institution between January 2004 and December 2007 were analyzed. RESULTS: out of 699 cycles resulting in oocyte retrieval, 193 produced a live birth (27.6%). Women who achieved a live birth had a significantly shorter stimulation phase (11.1 vs. 11.5 days, respectively). Multivariable analysis suggested that 13 days or longer of stimulation decreased the likelihood of a live birth by 53% as compared to cycles that were 10-12 days long (odds ratio [OR] 0.47; 95% confidence interval [CI]: 0.30-0.75) after adjustment for female age, maximum historical FSH, total dose of gonadotropin received, oocytes retrieved, embryos transferred, antagonist suppression and PCOS diagnosis. CONCLUSIONS: prolonged duration of gonadotropin stimulation is an independent negative predictor of ART success in our cohort.

Overweight men: clinical pregnancy after ART is decreased in IVF but not in ICSI cycles.

PURPOSE: To evaluate if elevated male body mass influences success after assisted reproductive technologies METHODS: Retrospective study of 290 cycles. RESULTS: Male body mass index greater than 25.0 kg/m² was associated with significantly lower clinical pregnancy (53.2% vs. 33.6%). Multivariable logistic regression indicated that the likelihood of clinical pregnancy was decreased if the male partner was overweight after in vitro fertilization but not after intracytoplasmic sperm injection (odds ratios: 0.21 [0.07-0.69] vs. 0.75 [0.38-1.49], respectively) after adjustment for number of embryos transferred, sperm concentration, female age and body mass. CONCLUSION: In this cohort, overweight status of the male partner was independently associated with decreased likelihood of clinical pregnancy after in vitro fertilization but not after intracytoplasmic sperm injection. A detrimental impact of higher male body mass was observed after adjusting for sperm concentration, suggesting that intracytoplasmic sperm injection may overcome some obesity related impairment of sperm-egg interaction.