OBJECTIVE: There is a movement toward single embryo transfer (SET) in assisted reproduction (ART) to avoid multiple births. Most centers in the USA transfer 2-3 embryos in women <40, resulting in high twin rates. Since 2007 we have had a strict 2 embryo (DET) embryo transfer (ET) policy for women <38, with an increasing use of SET. This study aimed at identifying cycle characteristics resulting in twin deliveries as a means of counseling patients to have eSET to avoid a twin pregnancy. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Transfer and outcome data for 2007/2008 in women <38 with DET, were analyzed. Excluded were donor, PGD/PGS and SET cycles. Cycles were analyzed for risk for twins. RESULTS: 504 embryo transfers in 538 cycles resulted in 219 ongoing (>20 weeks) or delivered cycles (43 % of ET) with 73 twin pregnancies (33% of pregnancies). Age was significant for twins; 52/73 (71%) <35 and 21/73(29%) 35-37 years. The risk of twins in a pregnancy cycle for <35 was 3.3 and for 35-37 was 0.4. BMI was significant for twin with BMI<20, 18%; 20-30, 35%; 30-35, 29% and >35, 5%. Cycle number was significant, with higher twin rates on first cycle and with repeat cycle after delivery. The total number of oocytes, was not significant but the number of fertilized oocytes was.Table 1The impact of total number of embryos on twin rates in DET cycles.≤5 Embryos>5 EmbryosAgeTotalSingletonTwinTotalSingletonTwin<3544/112 39%32/44, 73%12/44, 27%∗Data is presented as delivery/ transfer (%), P<0.05.111/234, 48%71/111, 64%40/111, 36%35-3720/74, 27%13/20, 65%7/20, 35%44/84, 52%30/44, 68%14/44, 32%∗ Data is presented as delivery/ transfer (%), P<0.05. Open table in a new tab CONCLUSIONS: The risk of twins with a DET is increased when there are >5 embryos available, regardless of age. If the woman is <35, has >5 embryos, BMI between 20 and 30, on their first cycle a DET results in a 55% delivery rate but a 41% chance a pregnancy being twin (21/92 ET, 51 pregnancies). These patients should be counseled for an elective single embryo transfer.

OBJECTIVE: eSET is recommend to lower multiple gestation yet few programs adopt its use due to concern of lower pregnancy rates. Identifying the clinical parameters resulting in pregnancy success with eSET will encourage its use. The aim of this study was to identify the clinical parameters resulting in successful pregnancy following eSET. DESIGN: Retrospective. MATERIALS AND METHODS: SET and eSET in women <38 yo were evaluated by: diagnosis, stimulation, day of hCG, maximum E2, and total FSH given. Ongoing/delivered pregnancy was the endpoint. RESULTS: 127 SET cycles in 397 transfer cycles resulted in 51 (40%) deliveries; 34 were non-selective SETs resulting in 8 (23.5%) deliveries; and 43/93 (46%) eSET delivered. Agonist and antagonist cycles afforded similar success rates (46% vs 43%). OCP with antagonist cycles was beneficial (43% vs. 33%; P<0.05) but detrimental in agonist cycles (36% vs. 50%; P<0.01). Total FSH had a significant effect: <1000IU, delivery rate; 20%; 1001-1500IU, 67%; 1501-2000IU, 70%; 2001-3000IU, 53% and >3000IU, 51%. Max E2 was significant at>4000 pg/mL (P<0.01) with less deliveries, 50% vs. 20%. Day of hCG, total FSH, and days of FSH resulted in decreased delivery rates: <10 days, 50%; 10 days, 42%; >10 days 32% (P<0.05). The infertility diagnosis for SET and eSET significantly effected delivery rates (table).TableDiagnosis versus SET and eSET outcome.DiagnosisNSETeSETMale Factor4652%55%∗P<0.05 vs others;Tubal2148%60%∗P<0.05 vs others;§P<0.01 vs SET.Endometriosis837.5%50%∗P<0.05 vs others;§P<0.01 vs SET.PCOS2528%39%Uterine520%25%Unexplained1533%36%Diminished Ovarian Reserve50%0%RPL2(50%)(100%)∗ P<0.05 vs others;§ P<0.01 vs SET. Open table in a new tab CONCLUSIONS: Patient diagnosis influenced outcome in eSET, with tubal and male factor resulting in the highest delivery rates. The day of hCG, total dose of FSH and the maximum E2 level all effect outcome. The type of stimulation did not impact outcome, except pre-treatment with OCP. Clinical parameters within a cycle are important in selecting patients for eSET.

Preimplantation genetic diagnosis for aneuploidy screening (PGS) is suggested to improve pregnancy rates and decrease pregnancy loss in infertility patients. The objective of this study was to compare the outcomes of poor prognosis PGS patients who either did or did not proceed with PGS to identify patients that may benefit from PGS. Retrospective analysis of PGS cycles and PGS cycles converted to standard IVF in 2006. PGS for poor prognosis patients was recommended in all cycles. Poor prognosis was defined as advanced maternal age (≥38) or repeat IVF failure (≥3 failed IVF). Low responders within this group were defined as having less than 6 2PNs. Good responders had ≥6 2PNS. PGS was performed in 70 cycles, 53 cycles were converted without PGS. Reasons for conversion were: less than 6 2PN (n = 41), less than 4 embryos for biopsy on Day 3 (n = 9), or patient preference (n = 3). PGS patients had embryos biopsied on day 3 with euploid embryos transferred on day 5. Converted PGS patients had transfers on day 2 (n = 35) or 3 (n = 18). Chi Square was used for statistical analysis. PGS patients were significantly less likely to have an embryo transfer and showed a trend towards lower loss rates for all and higher ongoing pregnancy rates in good responders only. Low responders had a greater likelihood of success per cycle without PGS while good responders had slightly greater pregnancy success following PGS. Table 1PGS vs. PGS conversionsPGS low respondersConverted low respondersPGS good respondersConverted good respondersN20415012Mean Age40.239.539.040.6Mean Cycle #2.82.74.02.9Mean # 2PN3.33.09.77.0# Transfers (%)6 (30) P<0.00141 (100)35 (70) P<0.0512 (100)Mean transferred1.32.31.03.4+hCG (%ET, cycle)1 (17, 5)14 (34, 34)8 (23, 16)3 (25, 25)FHB (%ET, cycle)1 (17, 5)9 (22, 22)7 (20, 14)1 (8, 8)Loss (% ET, cycle)05 (35, 35)1 (3, 2)2 (17, 17)Ongoing (% ET, cycle)1 (17, 5)8 (20, 20)6 (17, 12)1 (8, 8) Open table in a new tab PGS may be an effective selection tool for poor prognosis patients that are good responders. Low responders were likely to have normal embryos transferred without PGS because of the low embryo number eliminating the need for selection. These patients were more likely to have a baby but also more likely to have a loss. PGS should be considered as a tool for reducing nlosses rather than a method for improving the take home baby rate in poor prognosis patients.

ObjectivePublished studies in 1991 reported gonadotropin IUI and IVF live birth rates to be similar. Insurance companies in mandated states have used these prior studies to design criteria for IVF approval; today this often requires the patient complete at least three FSH/IUI cycles before IVF approval. Calculations of IUI versus IVF outcome and cost-effectiveness must incorporate timely pregnancy rates. SART reported an IVF pregnancy rate/retrieval of 15.2% in 1991 vs. 32.6% in 2002. This doubling of IVF pregnancy rates prompts re-evaluation of prior comparisons. This study reviews pregnancy rates in high-responding gonadotropin IUI cycles emergently converted to IVF. These converted cycles provide an initial comparison for fast track versus systematic treatment of patients, where cost and pregnancy outcome are to be considered.DesignA retrospective analysis of IVF and FSH/IUI data in 2004 in a private clinic in an insurance mandated state.Materials and methodsFour patient groups (divided into > and < 38 y.o.) were analyzed for delivery rates: 1) first time IUI cycles 2) total (1-3) IUI cycles; 3) IUI cycles emergently converted to IVF due to ≥ 5 mature follicles present after stimulation; and 4) first time IVF cycles. The delivery/ongoing pregnancy rates were computed. Chi-square statistical comparisons were made.ResultsTabled 1* P<0.01, ** P<0.001ConclusionHigh-responding gonadotropin IUI cycles should be converted to IVF. The increased pregnancy rate in this converted group as compared to first time IVF patients also suggests possible effects of patient selection, down-regulation or FSH acclimatization. The favorable pregnancy rates in the converted cycles also prompts re-evaluation of required FSH/IUI treatment prior to IVF approval in insurance mandated states. ObjectivePublished studies in 1991 reported gonadotropin IUI and IVF live birth rates to be similar. Insurance companies in mandated states have used these prior studies to design criteria for IVF approval; today this often requires the patient complete at least three FSH/IUI cycles before IVF approval. Calculations of IUI versus IVF outcome and cost-effectiveness must incorporate timely pregnancy rates. SART reported an IVF pregnancy rate/retrieval of 15.2% in 1991 vs. 32.6% in 2002. This doubling of IVF pregnancy rates prompts re-evaluation of prior comparisons. This study reviews pregnancy rates in high-responding gonadotropin IUI cycles emergently converted to IVF. These converted cycles provide an initial comparison for fast track versus systematic treatment of patients, where cost and pregnancy outcome are to be considered. Published studies in 1991 reported gonadotropin IUI and IVF live birth rates to be similar. Insurance companies in mandated states have used these prior studies to design criteria for IVF approval; today this often requires the patient complete at least three FSH/IUI cycles before IVF approval. Calculations of IUI versus IVF outcome and cost-effectiveness must incorporate timely pregnancy rates. SART reported an IVF pregnancy rate/retrieval of 15.2% in 1991 vs. 32.6% in 2002. This doubling of IVF pregnancy rates prompts re-evaluation of prior comparisons. This study reviews pregnancy rates in high-responding gonadotropin IUI cycles emergently converted to IVF. These converted cycles provide an initial comparison for fast track versus systematic treatment of patients, where cost and pregnancy outcome are to be considered. DesignA retrospective analysis of IVF and FSH/IUI data in 2004 in a private clinic in an insurance mandated state. A retrospective analysis of IVF and FSH/IUI data in 2004 in a private clinic in an insurance mandated state. Materials and methodsFour patient groups (divided into > and < 38 y.o.) were analyzed for delivery rates: 1) first time IUI cycles 2) total (1-3) IUI cycles; 3) IUI cycles emergently converted to IVF due to ≥ 5 mature follicles present after stimulation; and 4) first time IVF cycles. The delivery/ongoing pregnancy rates were computed. Chi-square statistical comparisons were made. Four patient groups (divided into > and < 38 y.o.) were analyzed for delivery rates: 1) first time IUI cycles 2) total (1-3) IUI cycles; 3) IUI cycles emergently converted to IVF due to ≥ 5 mature follicles present after stimulation; and 4) first time IVF cycles. The delivery/ongoing pregnancy rates were computed. Chi-square statistical comparisons were made. ResultsTabled 1* P<0.01, ** P<0.001 * P<0.01, ** P<0.001 ConclusionHigh-responding gonadotropin IUI cycles should be converted to IVF. The increased pregnancy rate in this converted group as compared to first time IVF patients also suggests possible effects of patient selection, down-regulation or FSH acclimatization. The favorable pregnancy rates in the converted cycles also prompts re-evaluation of required FSH/IUI treatment prior to IVF approval in insurance mandated states. High-responding gonadotropin IUI cycles should be converted to IVF. The increased pregnancy rate in this converted group as compared to first time IVF patients also suggests possible effects of patient selection, down-regulation or FSH acclimatization. The favorable pregnancy rates in the converted cycles also prompts re-evaluation of required FSH/IUI treatment prior to IVF approval in insurance mandated states.

Objective: Preimplantation genetic diagnosis (PGD) is increasingly utilized to enable couples to build healthy families. Since 1998, we have utilized PGD for single gene defects, balanced translocations and aneuploidy screening in patients with both recurrent pregnancy loss and advanced maternal age. We present our experiences after the first 100 cycles in a private practice setting.Design: Retrospective quantitative analysis of 100 PGD cycles from February 1998 to March 2003 in a private IVF center.Materials and Methods: 100 IVF cycles were scheduled for PGD. Genetic counseling was provided for all patients. Indications for PGD included single gene defects, recurrent pregnancy loss and advanced maternal age (>40) with at least 2 prior failed IVF cycles. Day 3 single blastomere biopsies were fixed and shipped to either Reprogenetics, West Orange, NJ (9-panel aneuploidy screening or balanced translocations) or Wayne State University Molecular Medicine and Genetics, Detroit, MI (single gene defects). Genetic results were analyzed from 891 embryos and correlated with clinical IVF data including pregnancy rates. Rate differences were analyzed utilizing Chi-square analysis.Results: 98 cycles resulted in embryos for biopsy, 27 of these for recurrent pregnancy loss, 25 for balanced translocations, 11 for advanced maternal age, 5 for X-linked sex selection, and 30 for single gene defects (including 14 for cystic fibrosis, 4 for Huntington's, 3 for myotonic dystrophy, 3 for aplastic anemia, 2 for hemophilia, and 1 each for metachromatic leukodystrophy, ectodermal dysplasia, familial polyposis, and chronic granulomatous disease). There did not appear to be a learning curve with regards to blastomere biopsy as 73% of the total pregnancies occurred in the first 50 cycles. In 12 of the 98 cycles, no genetically normal embryos were available for transfer. Pregnancy rates per cycle (not per ET) are depicted below. Tabled 1Conclusion: Although time and labor intensive, PGD has shown to be a feasible technique to reduce the transfer of genetically defective embryos. Positive hCG rates are consistent with previously reported ESHRE PGD consortium rates (24.0%; 281/1171 PGD cycles). However, on-going pregnancy rates are reduced when compared to reported SART rates (25%) from non-PGD cycles. Further clinical trials will continue to define which group of patients may most benefit from PGD technology. Objective: Preimplantation genetic diagnosis (PGD) is increasingly utilized to enable couples to build healthy families. Since 1998, we have utilized PGD for single gene defects, balanced translocations and aneuploidy screening in patients with both recurrent pregnancy loss and advanced maternal age. We present our experiences after the first 100 cycles in a private practice setting. Design: Retrospective quantitative analysis of 100 PGD cycles from February 1998 to March 2003 in a private IVF center. Materials and Methods: 100 IVF cycles were scheduled for PGD. Genetic counseling was provided for all patients. Indications for PGD included single gene defects, recurrent pregnancy loss and advanced maternal age (>40) with at least 2 prior failed IVF cycles. Day 3 single blastomere biopsies were fixed and shipped to either Reprogenetics, West Orange, NJ (9-panel aneuploidy screening or balanced translocations) or Wayne State University Molecular Medicine and Genetics, Detroit, MI (single gene defects). Genetic results were analyzed from 891 embryos and correlated with clinical IVF data including pregnancy rates. Rate differences were analyzed utilizing Chi-square analysis. Results: 98 cycles resulted in embryos for biopsy, 27 of these for recurrent pregnancy loss, 25 for balanced translocations, 11 for advanced maternal age, 5 for X-linked sex selection, and 30 for single gene defects (including 14 for cystic fibrosis, 4 for Huntington's, 3 for myotonic dystrophy, 3 for aplastic anemia, 2 for hemophilia, and 1 each for metachromatic leukodystrophy, ectodermal dysplasia, familial polyposis, and chronic granulomatous disease). There did not appear to be a learning curve with regards to blastomere biopsy as 73% of the total pregnancies occurred in the first 50 cycles. In 12 of the 98 cycles, no genetically normal embryos were available for transfer. Pregnancy rates per cycle (not per ET) are depicted below. Tabled 1 Conclusion: Although time and labor intensive, PGD has shown to be a feasible technique to reduce the transfer of genetically defective embryos. Positive hCG rates are consistent with previously reported ESHRE PGD consortium rates (24.0%; 281/1171 PGD cycles). However, on-going pregnancy rates are reduced when compared to reported SART rates (25%) from non-PGD cycles. Further clinical trials will continue to define which group of patients may most benefit from PGD technology.

Objective: Initial phase III clinical trials of ganirelix in IVF patients did not report an effect of BMI on LH surges; however, the patient population was limited to a BMI between 18 and 29 kg/m2. This study examines the incidence of LH surge in IVF patients on ganirelix with a BMI >29 kg/m2. Design: Retrospective analysis of IVF clinical data. Materials/Methods: Seventy-six infertility patients, ranging in age from 26–46, were enrolled in a ganirelix IVF protocol. Ovulation induction involved clomiphene citrate (100 mg cycle days 2–6) with recombinant FSH (cycle day 2 until hCG Rx). Ganirelix was administered on cycle day 8 at a dose of 0.25 mg and continued daily until hCG Rx. Blood samples were obtained on cycle days 2,5, and daily from cycle day 8 until oocyte retrieval. Concentrations of 17 [Szlig]-estradiol, progesterone, and LH were analyzed with electrochemicoluminescence immunoassays. The intra-assay coefficient of variation for LH was 1.6%. An LH surge was defined as >10 IU/L. BMI was calculated by measured height and weight. A scatterplot of BMI and LH was produced and incidence of LH surge compared by Student’s t-test. Results: LH surges while on ganirelix occurred in 6 of the 76 patients. Two of these cycles were cancelled. Oocytes were retrieved in the remaining 4 cycles. One of the four retrieved cycles resulted in an on-going pregnancy. The LH surges occurred with a BMI range of 19.8 to 44.8; however, LH surges were more likely to occur when BMI >34 kg/m2. Of the 8 patients with BMI >34, three (37.5%) were with LH surges. Conclusions: Accurate dosing of the GnRH antagonist ganirelix is critical for IVF patients. A balance is needed between efforts to minimize LH surges at low doses versus minimizing potential detrimental effects on endometrial receptivity at higher doses. Patients with BMI >34 kg/m2 may require higher than standard doses of ganirelix to prevent LH surges.

Objective: Initial phase III trials comparing the GnRH antagonist, ganirelix acetate, with the GnRH agonist, leuprolide acetate, showed similar pregnancy rates in IVF patients; however, inclusion criteria for this trial required patients to be ≤39 years old and with FSH levels ≤ 10 IU/L. Poor responder infertility patients, who may not meet these criteria, have previously benefited from the traditional clomiphene/FSH ovarian stimulation. This study compares clomiphene/FSH pregnancy outcomes in poor responder IVF patients, treated with or without ganirelix therapy. Design: Retrospective analysis of IVF clinical data. Materials/Methods: Two hundred fifty-five poor responder IVF patients with prior failed leuprolide treated cycles were enrolled in a clomiphene (100 mg cycle days 2–6), recombinant FSH (cycle day 2 until hCG Rx) protocol. Seventy-eight patients were additionally prescribed ganirelix (0.25 mg qD, cycle day 8 until hCG Rx); the remaining 177 patients did not use ganirelix. Blood samples were obtained on cycle days 2,5 and daily from cycle day 8 until oocyte retrieval. Some non-ganirelix patients required twice daily blood monitoring in the peri-ovulatory period. Pregnancy outcomes were calculated and compared by Student’s t-test. Results: Comparison between the ganirelix and non-ganirelix groups showed no statistically significant difference with regard to age (mean = 37.9 years), lifetime peak FSH (mean = 10.8 IU/L), cycle start FSH (mean = 8.2 IU/L), number of prior failed IVF cycles (mean = 3.6), or presenting diagnosis. Pregnancy outcomes between the ganirelix and non-ganirelix groups (see table) were not significantly different. Comparative pregnancy outcomes in poor responders. legendlegendP > 0.05 for all groupings.CC/FSH/GanirelixCC/FSHPositive hCG27/78 (34.6%)53/177 (29.9%)Chemical Preg7/78 (9.0%)11/177 (6.2%)Missed SAB4/78 (5.1%)9/177 (5.1%)Ongoing Preg16/78 (20.5%)33/177 (18.6%)legend P > 0.05 for all groupings. Open table in a new tab Conclusions: Use of the GnRH antagonist, ganirelix, in poor responder IVF patients provides similar pregnancy outcomes to those seen with traditional clomiphene/FSH stimulation protocols. In addition, ganirelix permits more convenient cycle monitoring and control of oocyte retrieval scheduling. Previous concerns of decreased embryo implantation rates at higher GnRH antagonist dosing are not supported by the comparative pregnancy outcome results.

Objective: To test the utility of day 2 estradiol measured during the IVF stimulation cycle. Design: To give external validity, an unrestricted population was chosen and analyzed retrospectively with the outcome measure birth/ongoing pregnancy. Materials/Methods: Day 2 estradiols were recorded in 895 consecutive IVF cycles with flare GnRH-agonist/gonadotropin or clomiphene combined with gonadotropin/±GnRH-antagonist. Female age was 37.7 ± 4.1 years (mean ± SD) and lifetime IVF cycles were 2.7 ± 1.7. All diagnoses were included. Treatment was deferred (n = 80) for elevated FSH (20 ± 7 IU/mL). After starting treatment, 72 cycles (10%) were cancelled for poor response. Predictive values and a receiver operator characteristic (ROC) curve were calculated for estradiol from 10–100 pg/mL in increments of 10. Results: In 730 treated cycles, outcome was not different by 10 pg/mL increments of day 2 estradiol in the range 10–100. Predictive values and likelihood ratios were non-significant and an ROC curve did not find day 2 estradiol to be a useful test in the subset of patients selected for treatment. In treated cycles there was no correlation between estradiol and FSH and FSH did not confound outcome. However, in cancelled cycles there was a negative correlation between FSH and estradiol (r2 = 0.14, p = 0.01). In cases of persistent luteal function (progesterone = 5.3 ± 5 ng/mL) or functional ovarian cysts treatment was not started. With estradiol elevation alone, treatment was started according to individual physician discretion. In 17 of the 33 estradiol elevation alone cycles treatment was started (estradiol 105 ± 50, median 90) and in four there was successful outcome (estradiol = 85 ± 6). In 16 of the 33 estradiol elevation alone cycles treatment was not started (estradiol = 140 ± 55, median 125). Circumstances of Estradiol >80 pg/mL. Tabled 1CircumstancenEstradiolPersistent luteal function16105 ± 210Functional cyst18260 ± 160Elevated estradiol alone33120 ± 50 Open table in a new tab Conclusions: It is biologically plausible that elevated day 2 estradiol reflects disorded ovarian function. In the present trial a population at risk for reduced ovarian reserve was studied in the cycle of stimulation. If estradiol exceeded 80 pg/mL, 50% of cycles were associated with non-structural ovarian cysts or persistent luteal function and treatment was deferred. In cycles proceeding to treatment, outcome was unimpaired for day 2 estradiol ranging from 10–100 pg/mL. However, small sample size in increments beyond 80 pg/mL severely limited power. If elevated day 2 estradiol is associated with a reduced IVF prognosis, the threshold is 80 pg/mL. At this threshold, derangements of the early follicular phase are frequently observed.

Local anesthesia with conscious sedation is well accepted by patients and provides scheduling flexibility, cost containment, patient safety, and ease of recovery. We believe the technique should be offered to selected patients undergoing intrafallopian transfer. By adhering to specific guidelines for surgical technique and monitoring, the procedure is a safe and acceptable alternative to general anesthesia for laparoscopic intrafallopian transfers.