To evaluate In Vitro Fertilization (IVF) outcomes stratified by age in women who integrated Whole Systems Traditional Chinese Medicine (WSTCM).DESIGN: Secondary analysis of a retrospective patient cohort from 2005 to 2010.MATERIALS AND METHODS: A multi-modal intervention, WSTCM is individualized acupuncture combined with diet, lifestyle, nutritional supplements, and Chinese herbs, if appropriate.We reviewed 1,069 IVF patient charts to assess the effect of adjuvant WSTCM (N¼119) on IVF live births compared with IVF alone (N¼580) or day of ET acupuncture (N¼370) and stratified by age group (<35, 35-37, 38-40, 41-42, >43 years old).Donor egg (n¼225), frozen (N¼251), cycles with no transfer (n¼312) were excluded.The primary outcome was live birth.Groups were compared using Fisher exact and Chi-square, p<0.05 was significant.Treatment effect was assessed using multivariate logistic regression, adjusted by covariates associated with outcome.Nonsignificant covariates were removed from the model using a stepwise method.RESULTS: Demographics and characteristics were comparable on all variables except: total antral follicles (p¼0.0497),diminished ovarian reserve diagnosis (p¼0.01),other diagnosis (p¼0.03),prior IVF (p¼0.004),number of mature eggs (p¼0.02), and number of embryos transferred (p¼0.003).IVF augmented with WSTCM was associated with an increase in live births in 38to 40-year-old women compared with IVF alone (p¼0.04), and in 41-to 42year-old women compared to all cycles (p¼0.01).There were trends toward a significant difference in live births in the 38-40 age group compared with all cycles (p¼0.05), and clinically relevant differences in the <35 and 35-37 age groups with WSTCM compared with the other groups, though not significant.Confidence intervals were broad, therefore larger populations are needed to confirm these observations.CONCLUSIONS: Age may be a consideration when integrating acupuncture or WSTCM with IVF and may benefit women aged 38 and older.In this retrospective study, adjuvant WSTCM and IVF was associated with increased odds of live birth in women aged 38 to 42 years old.Small group numbers limit the strength of these observations.

Patients undergoing IVF may receive either acupuncture or whole-systems traditional Chinese medicine (WS-TCM) as an adjuvant IVF treatment. WS-TCM is a complex intervention that can include acupuncture, Chinese herbal medicine, dietary, lifestyle recommendations. In this retrospective cohort study, 1231 IVF patient records were reviewed to assess the effect of adjuvant WS-TCM on IVF outcomes compared among three groups: IVF with no additional treatment; IVF and elective acupuncture on day of embryo transfer; or IVF and elective WS-TCM. The primary outcome was live birth. Of 1069 non-donor cycles, WS-TCM was associated with greater odds of live birth compared with IVF alone (adjusted odds ratio [AOR] 2.09; 95% confidence interval [CI] 1.36 to 3.21), or embryo transfer with acupuncture only (AOR 1.62; 95% CI 1.04 to 2.52). Of 162 donor cycles, WS-TCM was associated with increased live births compared with all groups (odds Ratio [OR] 3.72; 95% CI 1.05 to 13.24, unadjusted) or embryo transfer with acupuncture only (OR 4.09; 95% CI: 1.02 to 16.38, unadjusted). Overall, IVF with adjuvant WS-TCM was associated with greater odds of live birth in donor and non-donor cycles. These results should be taken cautiously as more rigorous research is needed.

Objectives: In 2007, Craig et al. reported the results of a randomized controlled trial in which a standardized acupuncture protocol performed on the day of embryo transfer (ET) resulted in lower pregnancy rates after in vitro fertilization (IVF). Between 2005 and 2007, the Craig protocol was used by one of the authors (LHR) at an infertility clinic unaffiliated with the Craig et al. trial. The objective was to retrospectively review clinic records to evaluate the effect of the Craig protocol in both donor and nondonor IVF cycles on four outcomes: (1) live births; (2) biochemical pregnancies; (3) adverse outcomes; and (4) live births in nondonor cycles across age groups established by the Society for Assisted Reproductive Technology. Design: The study design was a retrospective chart review. Setting: The study was conducted at a private infertility clinic. Patient(s): Patients underwent fresh, donor (N=70) or nondonor (N=402) IVF-ET. Intervention(s): The Craig protocol included the following points before ET: GV-20, CV-6, ST-29, SP-8, PC-6, LV-3; Shenmen and Brain on the left ear; and Uterus and Endocrine on the right ear. After transfer the points were LI-4, SP-10, ST-36, SP-6, KI-3; Uterus and Endocrine on the left ear; and Shenmen and Brain on the right ear. Main outcome measure(s): Live births (LB) beyond 24 weeks' gestation was the main outcome measure. Result(s): In nondonor IVF cycles, there were no differences in LB across age groups (odds ratio [OR]=1.04, 95% confidence interval [CI] 0.68–1.57), biochemical pregnancies (OR=0.60, 95% CI 0.27–1.33), or adverse outcomes (OR=0.63, 95% CI 0.31–1.26). In donor cycles, LB were higher in the acupuncture group (relative risk=1.31, 95% CI 1.02–1.71). Conclusions: In this observational study, the Craig protocol was not found to lower IVF LB. In fact, the Craig protocol was associated with higher LB in donor cycles. These findings should be considered cautiously because more adequately powered, randomized research is needed.

Objectives: In 2007, Craig et al. reported the results of a randomized controlled trial in which a standardized acupuncture protocol performed on the day of embryo transfer (ET) resulted in lower pregnancy rates after in vitro fertilization (IVF). Between 2005 and 2007, the Craig protocol was used by one of the authors (LHR) at an infertility clinic unaffiliated with the Craig et al. trial. The objective was to retrospectively review clinic records to evaluate the effect of the Craig protocol in both donor and nondonor IVF cycles on four outcomes: (1) live births; (2) biochemical pregnancies; (3) adverse outcomes; and (4) live births in nondonor cycles across age groups established by the Society for Assisted Reproductive Technology.Design: The study design was a retrospective chart review.Setting: The study was conducted at a private infertility clinic.Patient(s): Patients underwent fresh, donor (N = 70) or nondonor (N = 402) IVF-ET.Intervention(s): The Craig protocol included the following points before ET: GV-20, CV-6, ST-29, SP-8, PC-6, LV-3; Shenmen and Brain on the left ear; and Uterus and Endocrine on the right ear. After transfer the points were LI-4, SP-10, ST-36, SP-6, KI-3; Uterus and Endocrine on the left ear; and Shenmen and Brain on the right ear.Main outcome measure(s): Live births (LB) beyond 24 weeks' gestation was the main outcome measure.Result(s): In nondonor IVF cycles, there were no differences in LB across age groups (odds ratio [OR] = 1.04, 95% confidence interval [CI] 0.68-1.57), biochemical pregnancies (OR = 0.60, 95% CI 0.27-1.33), or adverse outcomes (OR = 0.63, 95% CI 0.31-1.26). In donor cycles, LB were higher in the acupuncture group (relative risk = 1.31, 95% CI 1.02-1.71).Conclusions: In this observational study, the Craig protocol was not found to lower IVF LB. In fact, the Craig protocol was associated with higher LB in donor cycles. These findings should be considered cautiously because more adequately powered, randomized research is needed.

This study retrospectively analysed array comparative genomic hybridization (CGH) results of 7753 embryos from 990 patients to determine the frequency of embryonic euploidy and its relationship with the cohort size (i.e. the number of embryos available for biopsy and array CGH analysis). Linear regression analysis was performed to assess the effect of cohort size on euploidy rate adjusted for the effect of female age. While increasing female age was associated with a significant decrease in euploidy rate of day-3 and day-5 embryos (P<0.001 for both groups), cohort size was not significantly associated with euploidy rate. Logistic regression analysis was performed to assess the effect of cohort size, adjusted for maternal age, on the likelihood of having at least one euploid embryo available for transfer. The odds of having at least one euploid embryo in an assisted cycle was significantly decreased by increasing female age (P<0.01 for both day-3 and day-5 embryos) and was significantly increased by every additional embryo available for analysis (P<0.001 for both day-3 and day-5 embryos).

Chromosome abnormalities cause the failure of a high proportion of embryos to implant or reach term. A correlation between follicular response and cohort size could indicate that ovarian reserve is correlated with egg or embryo quality and euploidy. The goal of this study was to determine the frequency of euploidy in cleaved embryos as well as blastocysts across maternal age groups according to the cohort size. Retrospective multicenter study. Ovarian stimulation protocols varied and were clinic-specific. More than 60 clinics were included in this study. Preimplantation genetic diagnosis was performed by array Comparative Genomic Hybridization (aCGH) following day-3 biopsy (649 cycles) or day-5 (blastocyst) biopsy (124 cycles). A total of 5435 day-3 embryos and 701 blastocysts were biopsied. Based on reanalysis of non-replaced embryos (n = 221), the technical error rate of aCGH was 3% for day-3 and 0% for day-5 biopsied embryos. See table:Tabled 1% Euploid Embryos According to Maternal Age and Cohort Size# embryos in cohortegg donor<3535-3940-42>42day-3 biopsy 1-450%43%18%∗P<0.0517%6% 5-740%38%26%15%5% 8-1065%35%28%15%8% >1047%47%32%∗P<0.0516%8%day-5 biopsy 1-450%55%50%36%20% 5-770%66%44%38%23% 8-1073%64%50%36%n/a >1058%57%n/an/an/a∗ P<0.05 Open table in a new tab The results do not support the notion that larger cohorts of embryos or aggressive stimulation regimes produce chromosomally inferior embryos. Furthermore, a smaller cohort of embryos reduces the absolute number of normal embryos available for fresh/frozen-thawed transfers while reducing the cumulative chances of pregnancy. Increasing the cohort size when possible, combined with comprehensive chromosome assessment and embryo selection followed by high yield freezing or vitrification procedures may optimize single embryo transfer and increase cumulative pregnancy rates.

Background: Seventy percent of embryos of women of advanced maternal age (AMA) and 50% of their blastocysts are chromosomally abnormal. These abnormalities contribute to low implantation rates and high miscarriage rates with increasing maternal age. Although few dispute the hypothesis that preimplantation genetic diagnosis should improve ongoing pregnancy rates, differences in methodology have yielded conflicting results when day 3 biopsy and fluorescence in situ hybridization (FISH) analysis have been used. Recent studies with comparative genome hybridization (CGH) combined with blastocyst biopsy and replacement on the next cycle have provided very high ongoing pregnancy rates (80%) and implantation rates (60%). However, CGH is not compatible with day 3 biopsy and day 5 replacements. A superior technique is array CGH (aCGH), which can provide results in 24 hours for all chromosomes per multiple loci. Objective(s): To report the first pregnancy results using aCGH. Materials and Method(s): Array CGH was performed on 46 patients from three fertility centers. The average maternal age was 37. Indications were AMA (≥38, n = 22), recurrent pregnancy loss (RPL), or other and age >38 years old (n = 24). A total of 465 embryos were analyzed. Two different DNA amplification methods were used. Some abnormal embryos were reanalyzed by FISH for those chromosomes found abnormal by aCGH to determine the error rate of aCGH. All embryos were replaced on day 5. Result(s): With the initial amplification method, 12% (n = 163) of single blastomeres did not produce results, compared with only 2% (n = 302; P<.001) with the second method, which is the one currently in use. In total, 465 embryos were biopsied, of which 431 gave aCGH results. Of these, 40.1% were normal (28% in the AMA group and 51% in the rest). After reanalyzing 87 abnormal embryos, six were normal by FISH (6.9% error rate). We had pregnancy outcomes in 30/46 of the patients. Of those, 71% (15/21) and 33% (3/9) of RPL (or other) and AMA patients, respectively, become pregnant (+sac). Implantation rates were, respectively, 64% (23/36) and 40% (4/10). Conclusion(s): We report the first pregnancies in the United States after aCGH of cleavage-stage embryos. The current amplification method proved to be very efficient in amplifying single cells (2% no amplification). The error rate (6.9%) was identical to our FISH error rate and was attributed to the reported 7% of mosaics with <50% abnormal cells. The implantation and pregnancy rates were superior to our FISH results but inferior to those reported by day 5 biopsy CGH results, indicating that day 5 may be a better stage to biopsy embryos.

OBJECTIVE: To determine the clinical benefits of PGD using array comparative genome hybridization (aCGH) and day 3 biopsy. DESIGN: Comparative study. MATERIALS AND METHODS: Patients included had advanced maternal age (AMA) or recurrent pregnancy loss (RPL). PGD was performed using single-cell day-3 biopsy, aCGH, and day-5 transfer. 151 cycles of PGD were performed on women of average age 37.2 in 18 infertility centers. Each PGD patient was matched with the average pregnancy outcome of its fertility center for non-PGD patients of the same age of the PGD patient. Ongoing pregnancy was considered one that past second trimester. Non replaced embryos were reanalyzed by FISH with 19 probes to determine the error rate. RESULTS: Only 118/151 (78.1%) PGD cycles had normal embryos for transfer. Reanalysis of all cells of non-replaced embryos showed that 98% of them were correctly diagnosed. Only 1.3 embryos on average were replaced in the PGD group. The pregnancy rate for the PGD group was 46% per cycle and 59% per transfer compared with 37.6% per cycle (N.S.) and 38% per transfer (p<0.001). The ongoing pregnancy rate for the PGD group was 42% per cycle and 54% per transfer, compared with 31% (N.S.) and 31% (p<0.001), respectively for the control group. For RPL cycles (n-35) the ongoing pregnancy rate was 63% per cycle and 57% per transfer.Tabled 1pregnancy rate / cyclepregnancy rate / transferongoing pregnancy rate / cycleongoing pregnancy rate / transfercontrol38%38%31%31%PGD46%59%42%54%p valueNS<0.001NS<0.001 Open table in a new tab CONCLUSION: Many AMA patients undergo PGD as a mean to determine if they produce any normal embryos and if not to progress to egg donation. In this data set, 22% of AMA patients had no normal embryos. For patients with at least one normal embryo, the ongoing pregnancy rate was significantly improved after PGD with aCGH. IVF/PGD with aCGH may help women with no normal embryos to progress to egg donation and patients with normal embryos conceive with their own eggs.

ObjectivePolyvinylpyrrolidone (PVP) use during intracytoplasmic sperm injection (ICSI) has raised concerns that it may cause submicroscopic changes to spermatozoa and may be toxic to oocytes. We evaluated two alternative methods of mechanical immobilization of sperm during ICSI in order to reduce or eliminate the exposure of oocytes and spermatozoa to PVP without compromising survivability, fertilization, or embryo quality.DesignWe compared three different methods of sperm isolation during ICSI between December 2003 and June 2004. Sixteen cycles were examined in which at least 12 mature oocytes were obtained at time of retrieval. Differences in survivability, fertilization rate, pronuclear score, cleavage rate, embryo quality and viability were evaluated among the three methods.Materials and methodsA total of 192 oocytes were injected. For the Test Group (n=64 oocytes) the sperm samples were placed in culture media alone to avoid the use of PVP. The Rinse Group (n-64) involved immobilizing a sperm cell from a PVP droplet and then rinsing it in culture media prior to injection. The Control Group (n=64) used conventional practices of exposure to PVP during ICSI. A single experienced clinician performed all procedures. Differences among groups were analyzed by analysis of variance (ANOVA). A p value <0.05 was considered significant.ResultsThe Non-PVP Group had similar or highest survivability, fertilization, and cleavage rates compared to the other two groups although the differences were not significant.ConclusionTabled 1 ObjectivePolyvinylpyrrolidone (PVP) use during intracytoplasmic sperm injection (ICSI) has raised concerns that it may cause submicroscopic changes to spermatozoa and may be toxic to oocytes. We evaluated two alternative methods of mechanical immobilization of sperm during ICSI in order to reduce or eliminate the exposure of oocytes and spermatozoa to PVP without compromising survivability, fertilization, or embryo quality. Polyvinylpyrrolidone (PVP) use during intracytoplasmic sperm injection (ICSI) has raised concerns that it may cause submicroscopic changes to spermatozoa and may be toxic to oocytes. We evaluated two alternative methods of mechanical immobilization of sperm during ICSI in order to reduce or eliminate the exposure of oocytes and spermatozoa to PVP without compromising survivability, fertilization, or embryo quality. DesignWe compared three different methods of sperm isolation during ICSI between December 2003 and June 2004. Sixteen cycles were examined in which at least 12 mature oocytes were obtained at time of retrieval. Differences in survivability, fertilization rate, pronuclear score, cleavage rate, embryo quality and viability were evaluated among the three methods. We compared three different methods of sperm isolation during ICSI between December 2003 and June 2004. Sixteen cycles were examined in which at least 12 mature oocytes were obtained at time of retrieval. Differences in survivability, fertilization rate, pronuclear score, cleavage rate, embryo quality and viability were evaluated among the three methods. Materials and methodsA total of 192 oocytes were injected. For the Test Group (n=64 oocytes) the sperm samples were placed in culture media alone to avoid the use of PVP. The Rinse Group (n-64) involved immobilizing a sperm cell from a PVP droplet and then rinsing it in culture media prior to injection. The Control Group (n=64) used conventional practices of exposure to PVP during ICSI. A single experienced clinician performed all procedures. Differences among groups were analyzed by analysis of variance (ANOVA). A p value <0.05 was considered significant. A total of 192 oocytes were injected. For the Test Group (n=64 oocytes) the sperm samples were placed in culture media alone to avoid the use of PVP. The Rinse Group (n-64) involved immobilizing a sperm cell from a PVP droplet and then rinsing it in culture media prior to injection. The Control Group (n=64) used conventional practices of exposure to PVP during ICSI. A single experienced clinician performed all procedures. Differences among groups were analyzed by analysis of variance (ANOVA). A p value <0.05 was considered significant. ResultsThe Non-PVP Group had similar or highest survivability, fertilization, and cleavage rates compared to the other two groups although the differences were not significant. The Non-PVP Group had similar or highest survivability, fertilization, and cleavage rates compared to the other two groups although the differences were not significant. ConclusionTabled 1

Purpose: To determine whether donor oocyte cytoplasm transferred into the oocytes of women ≥40 years or with diminished ovarian reserve would enhance embryo quality, implantation, or pregnancy rates.

Objective: To determine whether vaginally administered Viagra® could improve endometrial development and pregnancy rates in poor prognosis patients after a preliminary report suggested improved success using intravaginal Viagra in women with poor endometrial development during prior failed assisted reproductive cycles. Design: Randomized, third-party blinded, placebo-controlled crossover study. Materials/Methods: Patients with an endometrial thickness <6.5 mm in at least one prior CED cycle were offered participation in an IRB-approved, randomized, blinded, crossover study of supplemental vaginal Viagra®. Subjects were randomized to receive pharmacy prepared and blinded Viagra® or placebo suppositories. Subjects were down-regulated with Lupron® or withdrawn from hormone replacement therapy then administered intramuscular estradiol valerate 4 mg every three days, for two weeks. If endometrial thickness was ≥6.5 mm, frozen embryos were thawed and transferred. If the endometrial thickness was ≤6.5 mm, they had a Provera™-induced withdrawal bleed while maintaining Lupron®. They restarted intramuscular estradiol valerate with the alternate vaginal suppository for two weeks If the endometrial thickness was ≥6.5 mm, embryo thaw and transfer occurred otherwise the study ended. Results: Ten patients enrolled in the study. The mean endometrial thickness in pre-study cycles was 5.53 ± .26 mm and a sample size determination to achieve 80% power that Viagra® would not increase the mean endometrial thickness to 6.5 mm was 10 subjects. Study results are listed in the following table. The endometrial thickness was similar (p =.65) with or without Viagra® administration. The statistical power that the endometrial thickness did not increase from the baseline 5.5 mm by 1 mm to 6.5 mm was 84%. Only one patient achieved a significant endometrial improvement allowing embryo thaw and transfer, unfortunately, both embryos were non-viable. Subject 9 spontaneously conceived two months after completing the study. Tabled 1Cycle TypeNumber of SubjectsAge (Years)Prior ThicknessThickness without Viagra®Thickness with Viagra®IVF536.6 ± 1.65.9 ± 0.2 mm5.5 ± 0.3 mm5.8 ± 0.5 mmDonor Egg547.9 ± 1.05.1 ± 0.5 mm5.0 ± 0.5 mm5.1 ± 0.5 mmCombined1042.3 ± 2.15.5 ± 0.3 mm5.3 ± 0.3 mm5.4 ± 0.4 mm Open table in a new tab Conclusions: Vaginally administered Viagra® did not improve endometrial development during CED cycles when compared to placebo in this randomized, blinded, placebo-controlled trial. Supported by: Genetics & IVF Institute.

Objective: To compare the number of metaphase II (MII) oocytes retrieved in matched oocyte donation cycles following injection of Ovidrel® 250 mcg or hCG 10,000 IU. Design: In accordance with our clinical protocol, either triggering drug was administered subcutaneously (SQ) 34 hours prior to oocyte retrieval. A retrospective comparison of 44 matched oocyte donation cycles from February through December 2001 was conducted. Each of 22 oocyte donors served as their own matched control. Only intracytoplasmic sperm injection (ICSI) cycles were included in the study allowing for verification of polar body status. Materials/Methods: Anonymous donors were given subcutaneous injections of 250 mcg Ovidrel®in the first cycle and 10,000 IU HCG in a subsequent cycle for oocyte retrieval 34 hours post injection. All intact oocytes were subjected to 80 IU of Hyaluronidase (Sigma H-3757) in Hepes Buffered Earles (HBE) to disperse and remove the corona-cumulus complexes. Cleaned oocytes were observed for presence or absence of a polar body and maturational status was recorded. Assessment for normal fertilization was carried out 16–18 hours post injection. Data were statistically analyzed using t-tests and Mann-Whitney U tests as appropriate. Results: In anonymous oocyte donation cycles where Ovidrel® SQ was administered as the triggering medication, 64% of intact oocytes retrieved were MII. In the subsequent cycles using the same set of donors, but administering 10,000 IU HCG SQ, the MII recovery rate was 84%. Fertilization for Ovidrel® and HCG was 61% with 7.1 embryos available per patient and 68% with 10.5 embryos per patient respectively. The absence of sufficient numbers of MII oocytes at time of oocyte recovery adversely affects the clinical and laboratory processes. Embryologists returned to assess oocyte maturity and carry out injections throughout the night. Delayed injections caused changes in timing regarding fertilization assessment, and frequently in timing of transfers. Fortunately, pregnancy rates remained unaffected in the fresh transfer cycle. Table TableMatched Cycle Outcomes for Oocyte DonorsIntact OocytesMII OocytesFertilization RateEmbryos per PatientClinical PregnanciesOvidrel308197 (64%)61% (±2.7)7.1 (±4.7)50% (11/22)HCG352294 (84%)68.5% (±2.8)10.5 (±5.6)54.5% (12/22)P value0.18NSNSNS Open table in a new tab Conclusions: When given 34 hours prior to retrieval Ovidrel ® resulted in a decrease in MII oocytes available for injection at time of retrieval when compared with HCG. Supported by: Genetics & IVF Institute.

Purpose: To assess the effectiveness of outpatient treatment of Ovarian Hyperstimulation Syndrome associated with ascites. Methods: Forty-eight patients diagnosed with ovarian hyperstimulation and ascites from 2246 consecutive in vitro fertilization cycles were retrospectively studied. Patients were treated with outpatient transvaginal culdocentesis and rehydration with intravenous crystalloids and albumin every 1–3 days until resolution of symptoms or hospitalization was required. Outcomes measured included incidences of hospitalization, pregnancy outcomes, cycle characteristics, and oocyte donors versus nondonors comparisons. Results: No complications occurred from outpatient treatments, and 91.6% of patients avoided hospitalization. The pregnancy rate in patients undergoing transfer was 84.7%, and the spontaneous loss rate was 16%. Overall, the estradiol on day of hCG was 4331 pg/mL (range 2211–8167), ascites removed was 1910 cm3 (122–4000), and number of outpatient treatments was 3.4 (1–14). Nondonors averaged more outpatient treatments than donors (3.97 vs. 1.85), but similar rates of hospitalization (3/35 vs. 1/13). Conclusions: Outpatient treatment consisting of culdocentesis, intravenous rehydration, and albumin minimized the need for hospitalization in hyperstimulated patients.

Purpose: The purpose was to determine whether the number of embryos available for transfer following IVF in women over age 39 predicted a successful pregnancy outcome.

Objective: To evaluate the clinical outcome of in vitro fertilization (IVF) treatment cycles from individual oocyte donors who underwent multiple sequential donations.Methods: We reviewed clinical outcome data from sequential anonymous oocyte donation cycles using donors who underwent multiple IVF stimulations. Donors were grouped by the interval between cycles and the cycle number (rank). The primary outcome measure was delivery rate by individual donor per retrieval from the combined derivative fresh and frozen embryo transfers.Results: Duration and amount of gonadotropin therapy and the fertilization rates did not correlate significantly with the interval between cycles or cycle rank. Cumulative delivered pregnancy rates for cycles 1-6 were 51.5%, 54.6%, 50.5%, 51.5%, 51.1%, and 57.6%, respectively. Delivered pregnancy rates did not vary by interval between cycles.Conclusion: Young healthy presumed or proven fertile women can reliably donate oocytes for at least six cycles with the expectation of consistently high pregnancy rates. (Obstet Gynecol 2001;97:201-4. (C) 2001 by The American College of Obstetricians and Gynecologists.).

Objectives: IVF is an unquestionably important treatment for infertile couples. An undesirable but unavoidable risk of cotransferring several embryos is multiple gestations. Avoidance of all dizygotic multiple gestations cannot be achieved without a substantial reduction in cycle success rates. We evaluated our FET data for factors affecting the frequency of high-order multiple gestations. Design: Retrospective study design from a large private infertility center. Methods: Retrospective review of 1380 consecutive frozen-thawed non-donor embryo transfer cycles after conventional IVF or ICSI and 402 after donor IVF cycles. The number of 100%-intact embryos transferred was the most significant variable predicting a live-born delivery (stepwise logistic regression) and this variable was used to evaluate the probability of high-order multiple gestations. Results: 186 pregnancies resulted in delivery of one or more infants after 1380 non-donor FET cycles; and 90 followed 402 donor FET cycles. No high-order multiple gestation occurred with ≤2 100%-intact embryos in non-donor cycles or with <2 100%-intact embryos in donor cycles regardless of the number of additional <100%-intact embryos transferred. No high-order multiple births occurred when only 2 donor 100%-intact embryos were transferred alone. Donor cycles were more likely to result in pregnancy and high-order multiple births (p=0.04). legend% Embryos transferred with 100% blastomere survivallegend∗ In many cases one or more embryos with <100%-intact blastomeres were also transferred., legend∗∗ Only one quadruplet pregnancy occurred.Non-donorDonorNumber of cyclesLive- born pregTriplets+ (%) of preg)Number of cyclesLive- born preg∗∗Triplets+ (% of preg)02238.1%0%6116.4%0%14058.6%0%10512.4%0%240914.7%0%11823.7%10.7%326719.1%3.9%9328.0%3.7%46729.9%10.0%2343.5%20.0%5922.2%0%250.0%0%Total138013.5%2.1%40221.9%6.7%legend ∗ In many cases one or more embryos with <100%-intact blastomeres were also transferred.legend ∗∗ Only one quadruplet pregnancy occurred. Open table in a new tab Conclusions: Our data indicates that limiting the number of 100%-intact embryos transferred in FET cycles will decrease high-order multiple gestations particularly in donor FET cycles. For those couples who are particularly risk adverse, limiting non-donor FET cycles to ≤2 100%-intact embryos and donor FET cycles to one 100%-intact embryos plus any <100% embryos or 2 100%-intact embryos only will almost completely avoid the risk of high-order multiple gestation but at the expense of a reduction in liveborn infants. Overall, the risk of a high-order multiple gestations is well under 10% for both non-donor and donor FET cycles.

Objective: To determine the serum concentrations of enclomiphene and zuclomiphene across consecutive cycles of clomiphene citrate treatment in anovulatory infertile women.Design: Prospective cohort.Setting: Tertiary institutional infertility clinic.Patient(s): Fourteen consenting anovulatory infertile women receiving standardized, cyclic, incremental treatment with clomiphene citrate for ovulation induction.Intervention(s): Clomiphene citrate treatment (50-150 mg/d, cycle days 5-9), titrated to the minimum effective ovulation-inducing dose, was administered for three to six total cycles. Blood samples were obtained on cycle days 3 and 10 in each treatment cycle.Main Outcome Measure(s): Serum concentrations of enclomiphene and zuclomiphene.Result(s): Cycle day 3 zuclomiphene levels were below assay limits in all initial cycles, increased progressively across three consecutive cycles, and thereafter plateaued. Cycle day 3 enclomiphene concentrations were uniformly undetectable. Cycle day 10 enclomiphene levels increased with dose administered, but these observations were not statistically significant.Conclusion(s): Clomiphene citrate induction of ovulation results in an isomer-specific systemic accumulation of zuclomiphene across consecutive cycles of treatment. The combined maximum concentration of enclomiphene and zuclomiphene attained in practice approximates 100 nmol/L and is generally well below levels previously demonstrated to have adverse effects in vitro. (Fertil Steril(R) 1999;71:639-44. (C)1999 by American Society for Reproductive Medicine.).