John F. Hennessey

A formula for scoring human embryo growth rates in in vitro fertilization: Its value in predicting pregnancy and in comparison with visual estimates of embryo quality

Two systems for measuring embryo development in vitro were evaluated. One was a 1–4 scale based on a subjective evaluation of embryo quality (EQ) from microscopic appearance. In addition, a formula for scoring embryo growth rate in vitro was developed. The embryo development rating (EDR) was based on the ratio between the time at which embryos were observed at a particular stage after insemination and the time at which they would be expected to reach that stage in a hypothetical “ideal” growth rate with a cell cycle length of 11.9 hr. Using this scoring system, “normally” growing embryos scored 100. This approach was aimed at partially normalizing the data and allowed all embryos to be analyzed similarly regardless of the time of observation. Analysis of 1539 embryo replacements resulting in 232 clinical pregnancies showed that both EDR and embryo-quality scores were of value in predicting success, with clinical pregnancy most likely to eventuate from a combination of moderate to good EQ scores (2–4) coupled with average or above-average growth rates (EDR scores from 90 to 129). Poor-quality and very slowly or very rapidly growing embryos were underrepresented in cycles that proceeded to pregnancy. These inferences were based on all embryos transferred (mean, 2.73 per transfer cycle), and they were substantiated by an analysis of 33 pregnancies resulting from replacement of a single embryo and from 18 pregnancies in which all embryos scored the same with both systems. EQ and EDR were significantly associated with each other and together provide a valuable guide in predicting pregnancy, in selecting embryos for freezing, and in monitoring day-to-day performance in the in vitro fertilization (IVF) program.

Stress and semen quality in an in vitro fertilization program.

While a greater understanding is emerging of the psychological stresses of infertility treatment, little is known about the specific effects of these stresses upon the quality of the semen sample used at the fertilization stage in an in vitro fertilization and embryo transfer (IVF-ET) program. This study evaluated two semen profiles for each of 500 couples on IVF treatment. The first semen sample was collected in the couples pre-IVF workup, and the second sample was given by husbands after ovum aspiration, and used to inseminate the eggs in vitro. Comparisons of samples revealed that sperm density, total sperm count, and both quantitative and qualitative sperm motility were significantly lower in the second sample presented for IVF. For 91% of cases, there was no change across samples in assigned fertility index categories. However, 14 cases revealed a deterioration, falling from normal to pathologic, while 21 cases changed in semen character from normal in IVF workup to severely pathologic in IVF treatment. For these cases, the incidence of total fertilization failure in the procedure also dramatically increased. Several steps are discussed in the better management of patients with such declines in semen quality.

Multiple-sited (heterotopic) pregnancy after in vitro fertilization and gamete intrafallopian transfer *

Pregnancies occurring simultaneously in different body sites (heterotopic pregnancies) are a rare condition thought to occur in 1 of 30,000 spontaneous pregnancies. Individual cases may occur after in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). In the past 4½ years, our unit has performed 6,204 IVF/GIFT or pronuclear stage transfer cycles of treatment. Ten such pregnancies proven by surgical, ultrasound, and histological diagnosis have occurred. In the same period 640 IVF, 355 GIFT, and 6 pronuclear stage transfer clinical pregnancies were achieved. This suggests that the incidence of heterotopic pregnancy after assisted reproduction is closer to 1 of 100 pregnancies. Clinicians managing early complications of IVF, GIFT, and/or pronuclear stage transfer pregnancies should be aware of this relatively high incidence of concomitant intrauterine and extrauterine pregnancy.

Emotional aspects and support in in vitro fertilization and embryo transfer programs

Little is known about the emotional demands upon women of the step-by-step procedures characteristic of involvement in an in vitro fertilization/embryo transfer (IVF-ET) program. In this study, 77 women provided their perceptions of the emotional demands of IVF-ET and explanations for failed attempts, as well as describing their coping strategies and sources of emotional support. Nominated as the two most difficult stages of IVF were the wait for a possible pregnancy after the procedure and the blood tests and injections prior to hospitalization. Women were overly optimistic with a first attempt, with 70% being moderately to highly optimistic about success. Levels of optimism, however, generally declined across attempts. About half of the women intended to stop after four attempts, and almost all would stop after six treatment cycles. Women attributed their lack of success to a wide range of factors, including the low success rate, being anxious or stressed, bad luck, or problems associated with their condition and the procedure. Asked how they coped with the program, the women reported that the major strategy was to adopt the attitude that they might be successful in the long term. Other coping strategies involved keeping busy, staying calm, and seeking the support of other IVF women and husbands. Husbands were listed as the major source of emotional support, followed by other infertile women and nurses, counselors, and doctors. Finally, the majority of women believed that although they would be less fulfilled if they did not have a child through IVF-ET, nevertheless there were alternative sources of satisfaction which they would pursue. For most, continued infertility was not seen as detrimental to the quality of their marriages.

Toward understanding women's decisions to continue or stop in vitro fertilization: The role of social, psychological, and background factors

Two hundred fifty-four infertile women, all of whom had at least one in vitro fertilization-embryo transfer (IVFET) cycle, completed a structured questionnaire in which they provided background information and rated their beliefs about the outcomes of continuing on an IVF-ET program. Women not intending to continue IVF had older husbands, a larger proportion was mothers, and more of them, had an IVF pregnancy. Those stopping and continuing, however, did not differ in their ages, the length of their infertility, or their number of IVF attempts. Womens intentions about IVF were best predicted by their attitudes toward another attempt and their perceptions of social pressures. While women intending to continue or discontinue IVF had similar beliefs about the value of motherhood, the satisfactions in having children, the importance of happy marriages, and the need to be well adjusted; discontinuers were less optimistic about another attempt making them mothers, making their marriages happier, or improving the quality of their lives. Both groups of women, however, judged another IV attempt as likely to involve some stress, disappointment, and financial strain. In terms of their perceptions of social pressures, discontinuers also believed that their husbands, family, friends, and doctors did not think that they should have another IVF attempt. Finally, infertile womens attitudes about having another attempt and their perceptions of social pressures to try again or to stop were better predictors of their decisions about IVF than the background characteristics and fertility histories of women and their husbands. At the same time, together these variables explained only half of the variance in womens IVF decisions, and many other factors need to be considered in future research.

The predictive value of idiopathic failure to fertilize on the first in vitro fertilization attempt

OBJECTIVE To investigate the subsequent performance of patients with idiopathic fertilization failure on the first in vitro fertilization (IVF) cycle. DESIGN A retrospective study of 2,322 consecutive patients undergoing their initial IVF cycle. SETTING Advanced infertility treatment in an IVF/general infertility clinic. PATIENTS In 5 years, 94 couples with unexplained failed oocyte fertilization had 270 cycles of treatment. Each couples performance was tracked through subsequent cycles of treatment. INTERVENTIONS In vitro fertilization with husband and donor sperm. MAIN OUTCOME MEASURE(S) Investigated retrospectively after 5 years of data collection. RESULTS Sixty-five couples of the original 94 had a second IVF attempt. Fifty of these successfully fertilized oocytes with husbands sperm and 4 with donor sperm. Nineteen of the 65 couples who continued treatment achieved a pregnancy, and only one couple had continuing fertilization failure. CONCLUSIONS The prognosis in the study group was surprisingly favorable despite the initial failed IVF treatment cycle.

Fertilization of human oocytes in relation to varying delay before insemination

Fertilization and pregnancy rates in an in vitro fertilization and embryo transfer program were studied after a range of insemination times of between 1 and 26 hours after oocyte recovery. There was no significant variation in fertilization rate across this range. The pregnancy rate showed no significant variation for insemination between 3 and 16 hours after aspiration. However, it was disappointing at 2 hours (3%), and no pregnancies were achieved from the nine patients whose ova were inseminated 20 or more hours after aspiration. It is concluded that mature oocytes can be inseminated in vitro at any time between 3 and 16 hours after aspiration and still retain the same potential to produce a pregnancy.

Results using medium supplemented with either fresh or frozen stored serum in human in vitro fertilization

This study retrospectively compared the success of in vitrofertilization (IVF) among patients whose gametes had been incubated either in medium supplemented with freshly prepared pooled serum (331 cases) or in pooled serum which had been stored at −20°C prior to use (728 cases). Frozen stored serum was as effective as fresh serum with regard to the proportion of oocytes which fertilized and embryos which implanted and was not associated with any increased incidence of fetal loss during postimplantation development.