Jacob Mayer

Three years of in vitro fertilization at Norfolk

During the 3 years from 1981 to 1983, 319 consecutive patients in 560 cycles were treated in a program of in vitro fertilization at Norfolk. All patients were stimulated by human menopausal gonadotropin supplemented by human chorionic gonadotropin. There were transfers in 429 cycles, resulting in 105 pregnancies. Over the 3-year span, the pregnancy rate by cycle was 19%; by transfer, 25%; and by patient, 33%.

Cryopreserved embryos in the United States and their availability for research

OBJECTIVE To determine the number of embryos stored at assisted reproductive technology (ART) clinics in the United States and their current disposition. DESIGN A targeted survey instrument sent by the SART-RAND team to all medical practices providing in vitro fertilization services in the United States. RESULTS The SART-RAND team surveyed all 430 ART practices in the United States. Of these practices, 340 returned surveys for analysis. The data from these surveys were merged with data taken from the 1999 SART dataset, which contains information about practice size and success rates. Responding clinics reported a total of 396,526 embryos in storage as of April 11, 2002. The vast majority of the embryos (88.2%) were targeted for patient use. Small numbers of embryos were available for research, donation, destruction, quality assurance, or other uses. CONCLUSIONS Nearly 400,000 embryos are stored in the United States, the majority of which (88.2%) are targeted for patient use. Few are available for research (2.8%), limiting possible conversion into embryonic stem cell lines.

Aneuploidy frequencies in semen fractions from ten oligoasthenoteratozoospermic patients donating sperm for intracytoplasmic sperm injection

OBJECTIVE To determine aneuploidy frequencies in pellet and swim-up semen fractions from 10 infertile men with severe oligoasthenoteratozoospermia (OAT) who were donating sperm for intracytoplasmic sperm injection and to determine whether the swim-up isolation method would successfully separate aneuploid from haploid sperm. DESIGN Prospective study. SETTING Infertility clinic and molecular genetics laboratory. PATIENT(S) Ten patients with severe OAT. INTERVENTION(S) Cytogenetic analyses by fluorescence in situ hybridization to determine aneuploidy frequencies for chromosomes 1, 13, 18, 21, X, and Y in sperm from swim-up and pellet fractions. MAIN OUTCOME MEASURE(S) Gametic aneuploidy was scored in sperm fractions separated by the swim-up technique and clinical results after intracytoplasmic sperm injection were tabulated. RESULT(S) In all cases, chromosome aneuploidy levels in patients were significantly greater than in controls. The type and percentage of aneuploid sperm for all patients with OAT found in both swim-up and pellet fractions were not different, with the exception of diploid sperm, which remained in the pellet fraction. After ET, 2 (20%) of 10 couples achieved successful pregnancies. CONCLUSION(S) The data show significantly higher rates of diploidy, autosomal disomy and nullisomy, sex chromosome disomy and nullisomy, and total aneuploidy in sperm from all separated fractions obtained from all patients with OAT versus controls. This patient population with OAT may be at increased risk of producing aneuploid offspring.

Perifollicular blood flow Doppler indices, but not follicular pO2, pCO2, or pH, predict oocyte developmental competence in in vitro fertilization

OBJECTIVE To assess the relationships among perifollicular blood flow; follicular fluid pO2, pCO2, and pH; oocyte developmental capacity; preimplantation embryo quality. DESIGN Prospective study. SETTING Academic, tertiary care institution. PATIENT(S) Unselected, gonadotropin-stimulated IVF cycles. INTERVENTION(S) Color, pulsed Doppler analysis of perifollicular blood flow, and follicular pO2, pCO2, and pH determinations of randomly designated, mapped ovarian follicles. MAIN OUTCOME MEASURE(S) Fertilization and day 3 embryo cleavage and morphology. RESULT(S) Perifollicular vascularity indices were significantly and negatively correlated with day 3 embryo cleavage. Pulsatility index and S-D ratio also were significantly and negatively correlated with follicular pO2. The same correlation was found between resistance index and the fertilization rate of preovulatory oocytes. No relationship existed between follicular metabolic analysis and fertilization or embryo quality. The resistance index had a sensitivity of 0.57 and a specificity of 0.71 for the prediction of advanced embryo cleavage status. CONCLUSION(S) Results confirm and extend previous reports demonstrating that color, pulsed Doppler ultrasound analysis of individual preovulatory follicles during IVF therapy may provide an indirect index of the developmental competence of the corresponding oocyte. Although these methods may provide means to select embryos for transfer with the highest implantation potential, the moderate predictive power showed so far may limit their clinical applicability.

Male factor evaluation in in vitro fertilization: Norfolk experience

Thirty-three patients from the in vitro fertilization (IVF) program at Norfolk are critically reviewed. A battery of tests was designed and an endocrine investigation was carried out on these patients. The fertilization rate for preovulatory oocytes was lower than in the normal male population (39.6% versus 88.6%). When total concentration of sperm with rapidly progressive motility was less than 6 X 10(5), to fertilize several eggs together the fertilization rate was zero. No fertilization was obtained when the number of sperm with rapidly progressive motility recovered after the separation was less than 1.5 X 10(6). The hamster zona-free oocyte penetration test correlated well with the human IVF system. The other parameters investigated did not show good correlation. When fertilization was achieved, the results of the IVF procedure in the series reviewed rendered a 30.8% pregnancy rate per transfer in 26 transfers. Fifty percent of the pregnancies were normal (either ongoing or delivered). Thirty-seven percent were preclinical miscarriages, and 12.5% were clinical abortions. In the abnormal male population, higher concentrations of sperm per egg should be used for insemination for achievement of optimum fertilization rates. Once fertilization is obtained, the results do not differ substantially from the IVF population at large.

Does storage time influence postthaw survival and pregnancy outcome? An analysis of 11,768 cryopreserved human embryos

OBJECTIVE To evaluate the impact of cryopreservation storage duration on embryo survival, implantation competence, and pregnancy outcome. DESIGN Retrospective study. SETTING Academic tertiary-referral infertility center. PATIENT(S) In vitro fertilization patients and recipients of oocyte donation cycles who had cryopreserved embryos and underwent at least one thaw cycle from 1986 to 2007. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Postthaw survival proportion and implantation, clinical pregnancy, miscarriage, and live birth rates. RESULT(S) Length of storage time did not have a significant effect on postthaw survival for IVF or oocyte donation cycles, or for embryos frozen at the pronuclear or cleavage stages. There was no significant impact of the duration of storage on clinical pregnancy, miscarriage, implantation, or live birth rate, whether from IVF or oocyte donation cycles. Logistic regression analysis demonstrated that the length of storage time or developmental stage at freezing were not predictive of embryo survival or pregnancy outcome. Only oocyte age, survival proportion, and number of transferred embryos were positive predictors of pregnancy outcome. CONCLUSION(S) Cryostorage duration did not adversely affect postthaw survival or pregnancy outcome in IVF or oocyte donation patients.

Impact of different clinical variables on pregnancy outcome following embryo cryopreservation

In our programs 13 years of experience, more than 9000 embryos have been cryopreserved in gonadotropin-stimulated IVF cycles. Over 1500 thaw and transfer cycles have yielded a pregnancy rate of approximately 25%. Different ovarian stimulation regimens (various preparations of FSH. alone or in combination with hMG, with or without concomitant use of a GnRH agonist) did not influence embryo survival or pregnancy rate. Likewise, the application of oocyte/embryo micromanipulation techniques for assisted fertilization (ICSI for male infertility) or assisted hatching (performed selectively) did not have an impact on pregnancy results. Survival and transfer rates of embryos cryopreserved at pronuclear or cleaving stage did not differ significantly. However, implantation and pregnancy rates were higher with pronuclear embryo freezing (day-2 transfers) when compared to embryos frozen at the cleavage stage (day-3 transfers). This may be the result of patient selection and transfer policies. Similar implantation and pregnancy results were achieved in natural and estrogen progesterone supplemented transfer cycles. Initial experience with pronuclear freezing followed by transfer at the blastocyst stage appears to offer a very successful alternative for selected patients.

Standardization of grading embryo morphology

Standardization of morphologic assessment for an embryo grading system was developed and is being implemented by the Society for Assisted Reproductive Technology (SART). A recent European consensus conference of embryologists from Europe and America is working toward adopting an embryo classification system modeled similarly to that of SART that, if adopted, would produce a de facto international standard to aid cross-border collaboration.

Impact of transabdominal ultrasound guidance on performance and outcome of transcervical uterine embryo transfer.

AbstractPurpose: To determine the impact of transabdominal ultrasound guidance on embryo transfer during IVF therapy. Methods: Retrospective analysis of 823 consecutive embryo transfers. Three hundred and sixty-seven procedures performed with transabdominal ultrasound guidance were compared to 456 cases performed with the “clinical touch” method. Results: Ultrasound-guided embryo transfer yielded higher, but not statistically significant, clinical pregnancy (48% vs. 44%) and implantation rates (22% vs. 20%). The incidence of multiple pregnancies, ectopic and multiple pregnancy rates were similar. The frequency of negative factors typically associated with difficult transfers, such as requirement of use of tenaculum, and presence of blood or mucus in the catheter tip, were significantly lower in the ultrasound-guided group in comparison with the clinical touch group. Ultrasound-guided embryo transfer was associated with a significantly increased easiness of transfer performance; 95% of the transfers were rated as very easy in the ultrasound-guidance group compared to 87% in the clinical touch group. The use of a soft pass catheter was the only variable independently and significantly associated with pregnancy success (odds ratio = 2.74). Conclusion(s): Ultrasound-guidance facilitates embryo transfer and in combination with the use of a soft catheter should be implemented to optimize embryo transfer results.

In vitro fertilization in Norfolk, Virginia, 1980-1983

Three years of progress of the Vital Initiation of Pregnancy (VIP) Program in Norfolk is reported. No conception resulted from 41 oocyte aspirations during spontaneous menstrual cycles in 1980. An average of 3.7 oocytes per cycle, or a 73.5% recovery rate, resulted in 362 human menopausal gonadotropin/human chorionic gonadotropin-induced cycles from January 1981 to March 1983. Forty pecent of the oocytes recovered from these cycles were preovulatory, 35% atretic, and 25% immature. Immature oocytes were often matured in vitro, fertilized, and found to produce pregnancies. A total of 62 pregnancies occurred, which represents a 17 or 23% pregnancy rate, based on laporoscopies or embryo transfers, respectively. There were 11 preclinical and 7 clinical miscarriages. Twenty-nine normal babies have been delivered, including a set of twins. The remainder appears to be normally progressing pregnancies. Polyspermia was observed in 8.8% of the fertilizable oocytes.