Katharine V. Jackson

The number of eight-cell embryos is a key determinant for selecting day 3 or day 5 transfer

OBJECTIVE To select patients for day 3 vs. day 5 embryo transfer. DESIGN Retrospective analysis of assisted reproduction technology (ART) cycles comparing outcomes of day 3 and day 5 transfers. SETTING ART program of Brigham and Womens Hospital. PATIENT(S) Patients with day 3 or day 5 embryo transfers (n = 221 and 141, respectively). INTERVENTION(S) Cycles with eight or more zygotes were stratified by the number of eight-cell embryos available on day 3 (none, one or two, or three or more). MAIN OUTCOME MEASURE(S) Number of blastocysts, implantation rates, ongoing pregnancy rates, and number of fetal heart beats. RESULT(S) With no eight-cell embryos on day 3, 0% and 33% pregnancies resulted from day 5 vs. day 3 transfers. With one or two eight-cell embryos on day 3, ongoing and high order multiple rates were not different between day 3 and day 5 transfers. With three or more eight-cell embryos, day 5 transfer resulted in a decrease in multiple gestations but no difference in ongoing pregnancy rates compared with day 3 transfer. CONCLUSION(S) With no eight-cell embryos on day 3, a day 3 transfer is warranted. With one or two eight-cell embryos, any benefit of day 5 transfer appears to be equivocal. With three or more eight-cell embryos, day 5 transfer is recommended.

Effects of endometriomas on ooccyte quality, embryo quality, and pregnancy rates in in vitro fertilization cycles : A prospective, case-controlled study

Purpose:The effect of endometriomas on oocyte quality, embryo quality, and pregnancy rates in in vitro fertilization (IVF) cycles was evaluated.Methods:Forty-five women had “chocolate” cysts aspirated at the time of oocyte retrieval, and cyst fluid CA 125 levels were measured to ascertain presence of “true” endometriomas. Fifty-seven women without any complex cysts at the time of oocyte retrieval served as controls. IVF cycle outcome parameters were compared between the two groups.Results:Women with endometriomas experienced a significantly higher rate of early pregnancy loss compared to controls (47 vs 14%). There was also a trend toward fewer oocytes retrieved and fewer embryos reaching at least the four-cell stage 48 hr after retrieval in patients with true endometriomas vs controls.Conclusions:The presence of endometriomas at the time of oocyte retrieval is associated with increased rates of early pregnancy losses. The number of oocytes retrieved and the embryo quality may also be affected adversely in the presence of endometriomas.

Day 3 and day 5 morphological predictors of embryo viability

Controlling multiple pregnancies in patients undergoing artificial reproductive procedures requires consideration of single embryo transfers. Therefore, refinements for embryo evaluation are needed that select for the most developmentally competent embryo. The present study was designed to identify day 3 and day 5 morphological predictors of viability following transfers in which the morphology and fate of each embryo was precisely determined. Assessments on day 3 included cell number, and the extent of fragmentation and asymmetry, and on day 5, the developmental stage. Embryos resulting in a viable fetus at 11 weeks gestation were considered developmentally competent. The relationships among individual and collective embryo morphological characteristics were evaluated. Analysis of the interactions among morphological characteristics of embryos transferred on day 3 enabled identification of a multivariable selection order. Assessment of day 5 embryos revealed that expanding and expanded blastocysts exhibited comparable developmental potential that was superior to that of either morulae or early blastocysts. However, expanding or expanded blastocysts derived from 7-cell or 8-cell embryos were developmentally superior to those derived from other cleavage stages, regardless of fragmentation or asymmetry. Collectively, these findings further understanding of morphological predictors of viability, thereby improving the ability to select the most viable embryo for transfer.

Multinucleation in normally fertilized embryos is associated with an accelerated ovulation induction response and lower implantation and pregnancy rates in in vitro fertilization-embryo transfer cycles

OBJECTIVE To determine if multinucleation in normally fertilized embryos is indicative of poor developmental or clinical pregnancy prognosis and to examine the ovulation induction characteristics associated with multinucleation. DESIGN Retrospective review. SETTING A tertiary care institution. PATIENT(S) Patients undergoing IVF-ET cycles (exclusive of other assisted reproductive technologies). MAIN OUTCOME MEASURE(S) Cycles in which embryos had at least 1 multinucleated blastomere were compared with cycles in which all blastomeres exhibited no nucleus or a single nucleus (control). RESULT(S) When >50% of transferred embryos contained multinucleated blastomeres there was a significant reduction in implantation (3.4% vs. 14.7%), clinical pregnancy (9.1% vs. 29.1%), and live birth rates (7.5% vs. 27.6%) when compared with transfers of control embryos. In conjunction with this finding, multinucleate cycles had higher E2 levels and more follicles on the day of hCG administration, a higher number of oocytes retrieved, a higher fertilization rate, and more embryos transferred per patient than did the cycles that produced control embryos. When multinucleated embryos were present, but not transferred, the developmental capacity of the sibling embryo was reduced. CONCLUSION(S) The evaluation of nuclear status using simple light microscopy is predictive of embryo developmental capacity and should be included in the embryo scoring system. The presence of multinucleated blastomeres in normally fertilized embryos is associated with a more effusive response to gonadotropin therapy and is indicative of a poor developmental outcome and lower clinical pregnancy rates.

In vitro fertilization for cancer patients and survivors

OBJECTIVE To determine in vitro fertilization (IVF) outcome in cancer patients. DESIGN Retrospective record review. SETTING Academic, hospital-based assisted reproductive technology (ART) program. PATIENT(S) Sixty-nine women undergoing 113 IVF/gamete intrafallopian transfer (GIFT) cycles after cancer treatment in one partner, and 13 women undergoing 13 IVF cycles for embryo cryopreservation before chemotherapy/radiation. INTERVENTION(S) IVF, intracytoplasmic sperm injection (ICSI), assisted hatching, and gamete intrafallopian transfer as indicated. MAIN OUTCOME MEASURE(S) Delivery rate, spontaneous abortion rate, number of embryos cryopreserved, cancer diagnosis, systemic or local cancer treatment, female age, amount of gonadotropin used, treatment duration, peak estradiol level, and number of oocytes and embryos. RESULT(S) The women undergoing IVF after chemotherapy had poorer responses to gonadotropins than did the women with locally treated cancers even though they were younger (33.5 +/- 1.3 vs. 36.5 +/- 0.5 years; P<.05). The delivery rates after the women had undergone chemotherapy tended to be lower among the systemic treatment group than it was for the local cancer treatment group: (13.3% [2 of 15] vs. 40% [14 of 56, P=NS]). The women who had cryopreserved all embryos before chemotherapy produced more oocytes (18.7 +/- 3.2 vs. 14.5 +/- 1.2) and embryos (11.3 +/- 1.9 vs. 7.5 +/- 0.7) than did the women who had had a history of local cancer treatment. Male factor infertility as a result of cancer treatment is well treated with IVF or intracytoplasmic sperm injection, where indicated (32% delivery rate/cycle), with no difference between the frozen sperm banked before cancer treatment and fresh sperm produced after treatment. CONCLUSION(S) Chemotherapy diminishes the response to ovulation induction in assisted reproductive technologies. IVF with cryopreservation of embryos allows embryo banking before chemotherapy for women who have been newly diagnosed with cancer. Factors related to the partner affect the success of IVF for male factor infertility as a result of cancer treatment.

Glucocorticoid metabolism in human placenta, decidua, myometrium and fetal membranes☆

The metabolism of cortisone (E) and cortisol (F) by human placenta, decidua, myometrium, chorion and amnion during pregnancy was studied in vitro. Early pregnancy, midpregnancy and term placentae metabolized F efficiently yielding E as the major product. The capacity of the placenta to inactivate F to E was observed as early as the 8th week of pregnancy and there was a significantly higher (P less than 0.001) net production of E in early pregnancy placenta than in term placenta. In contrast to the placenta, midpregnancy and term decidua metabolized mainly E to F with a net production of F. Term chorion demonstrated an equal degree of oxidative and reductive glucocorticoid metabolism while term amnion and myometrium had negligible metabolic activity. Thus the net production of F from E by the decidual membrane unit is due to metabolic activity in the decidua as early as the 13th week of pregnancy and not to activity in the fetal membranes.

Prostaglandin E and F2α receptors in human myometrium during the menstrual cycle and in pregnancy and labor

The binding of prostaglandins E1 and F2 alpha has been studied in the human myometrium and cervix during the menstrual cycle and in the myometrium of pregnant patients at term before and during labor. Tritium-labeled prostaglandin E1 and F2 alpha binding was saturable and reversible. Scatchard analysis of tritium-labeled prostaglandin E1 binding was linear, which suggests a single class of high-affinity binding sites with an estimated apparent equilibrium dissociation constant of 2.5 to 5.4 nmol/L and inhibitor affinities of 0.9, 273, 273, and 217 nmol/L for prostaglandins E2, A1, B1, and F2 alpha, respectively. Scatchard analysis of tritium-labeled prostaglandin F2 alpha, binding was also linear, but the affinity of these binding sites was much lower, with an average dissociation constant of 50 nmol/L and inhibitor affinities of 1.6, 2.2, and 11.2 nmol/L for prostaglandins E1, E2, and A1, respectively. In nonpregnant patients, the concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were similar in the myometrium during the proliferative and secretory phases of the menstrual cycle, but the concentration of these sites was much lower in the cervix. The concentration of the tritium-labeled prostaglandin E1 binding sites was significantly lower in the myometrium of pregnant patients at term than in the myometrium of nonpregnant patients. The concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were not significantly different in the upper and lower myometrium of pregnant patients at term or in the myometrium of such patients before and during labor. The concentrations of the tritium-labeled prostaglandin F2 alpha binding sites during the menstrual cycle and in pregnancy at term were similar to those of tritium-labeled prostaglandin E1 binding sites. In addition to confirming the presence of specific prostaglandin E and F2 alpha binding sites in the myometrium, these data also suggest: that specific prostaglandin E binding sites are present in the cervix and that the concentrations and affinities of prostaglandin E binding sites do not change during the menstrual cycle and are similar before and during labor in pregnant patients at term.

The predictive value of discriminatory human chorionic gonadotropin levels in the diagnosis of implantation outcome in in vitro fertilization cycles

OBJECTIVE To determine if early serum hCG levels are predictive of implantation outcome in patients undergoing IVF-ET. DESIGN Retrospective study of IVF cycles using receiver operator characteristic curve (ROC) analysis. SETTING Tertiary-care, university hospital-affiliated IVF program. PATIENTS Three hundred fifty-one conception cycles were studied. INTERVENTIONS None. MAIN OUTCOME MEASURE Implantation failure, defined as chemical pregnancies, ectopic gestations, and first trimester abortions, or implantation success, defined as delivered singleton and multiple pregnancies, and second trimester abortions. RESULTS For each post-ET day 14 to 20, mean hCG levels of the implantation success group were significantly greater than implantation failure outcomes (P < 0.0001). Using ROC curve analysis, hCG cutoff values for each post-ET day were calculated for optimal discrimination of implantation failure from implantation success cycles. A patient with an hCG measurement greater than the calculated cutoff value had a > or = 90% chance of having an implantation success after IVF-ET. CONCLUSION Discriminatory hCG cutoff values may be useful in predicting implantation outcome in IVF-ET cycles and may guide clinicians in identifying those pregnancies at risk for adverse outcomes and instituting more intensive surveillance in this population. This information also may be useful in providing counseling to IVF patients regarding pregnancy prognosis and result in cost savings.

Fertilization and cleavage of mouse oocytes exposed to the conditions of human oocyte retrieval for in vitro fertilization

Ova from two strains of mice (a hybrid-inbred strain, B6D2F1, and a random-bred strain, CD1) were shocked by exposure to environmental conditions possibly encountered by human oocytes retrieved for in vitro fertilization (IVF). Shocked and control mouse ova were fertilized in vitro in either simple or complex media and zygote development to morulae and blastocyst stages compared with that of zygotes fertilized in vivo. Development of the hybrid-inbred zygotes following fertilization in the simple media of shocked and control ova was essentially the same as for ova fertilized in vivo (84 +/- 6.6, 89 +/- 1.6, 87 +/- 6.0% to the 2-cell stage and 89 +/- 5.2, 94 +/- 2.3, 99 +/- 1.0% of two cells to blastocysts, respectively); development in the complex media also was the same following fertilization of shocked and control ova (80 +/- 8.7, 90 +/- 2.7% to two cells and 33 +/- 3.5, 35 +/- 4.5% of two cells to blastocysts, respectively) but lower than that of in vivo zygotes (92 +/- 4.6 to two cells, 58 +/- 4.7 two cells to blastocysts). In contrast, the fertilization and development in the simple media of shocked and control random-bred ova was lower and more variable (90 +/- 5.8, 67 +/- 11.1% to two cells and 17 +/- 8.3, 42 +/- 13.6% two cells to blastocysts, respectively) than the development of in vivo zygotes (96 +/- 1.5% to two cells, 51 +/- 5.5 two cells to blastocysts).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of elevated serum progesterone during ovulation induction in in vitro fertilization-embryo transfer

AbstractObjective: Our purpose was to determine whether elevated progesterone (P) during ovulation induction in IVF-ET cycles is a poor prognostic factor for achieving pregnancy. Design: We retrospectively reviewed 672 consecutive IVF-ET cycles in which ovulation was performed using luteal LA downregulation and hMG. Setting: The ART program at the Brigham & Womens Hospital, a tertiary care institution, was the study setting. Main Outcome Measures: Patients were divided into groups by serum P levels at baseline, on stimulation day 5, on the day of hCG injection, and, on the day after hCG injection and the following parameters were compared: duration of luteal LA treatment, number of ampoules of hMG used, estradiol (E2) levels, number of follicles ≥12 mm, number of follicles ≥15 mm, number of oocytes, number of normal embryos, number of polyspermic embryos, fertilization rate, implantation rate, and clinical and ongoing/live birth pregnancy rates. Results: Based on serum P level, patients were divided into three groups: Group I, ≤0.31 ng/ml (conversion factor to SIU, 3.180); Group II, and >0.3 and <1.0 ng/ml and Group III, ≥1.0 ng/ml. Measureable P at baseline was associated with a higher cancellation rate, but no difference in other cycle outcome parameters. Progesterone >0.31 ng/ml on stimulation day 5 was associated with a higher fertilization rate in Groups II and III, but there was no difference in the clinical pregnancy or ongoing/live birth rates among the three groups. Based on P on the day of hCG administration, Groups II and III had significantly more oocytes and higher fertilization rates than did Group I, however, clinical pregnancy and ongoing/live birth rates were not significantly different. On the day after hCG, there was a trend toward a higher clinical pregnancy rate in Group III, which had younger patients, better follicular recruitment, and more embryos than Groups I or II, but these differences did not reach statistical significance. Conclusions: Serum P >0.31 ng/ml during ovulation induction reflects good follicular recruitment, and is not a predictor of IVF outcome.