A comparison of in vitro fertilization results after embryo transfer after 2, 3, and 4 days of embryo culture.

Embryo transfer results after a 2 to 4 day period of embryo culture were compared. Two thousand two hundred ninety-seven ETs, performed in 1991 and 1992, were analyzed. Ongoing pregnancy rates after 2, 3, or 4 days of embryo culture were 23.3%, 21.9%, and 26.4%, respectively. Multiple pregnancy rates were 36.2%, 38.8%, and 32.6% per ongoing pregnancy for the three groups, respectively. The implantation rate of 73 cavitating morulae on day 4 was surprisingly high (41%) compared with that of other developmental stages. Transfer after 4 days of culture gives the ability to recognize embryos with a very high implantation potential.

Doubling the human menopausal gonadotrophin dose in the course of an in-vitro fertilization treatment cycle in low responders: a randomized study.

The effect of doubling the human menopausal gonadotrophin (HMG) dose in the same treatment cycle in which the ovarian response after 5 days of ovarian stimulation with 225 IU/day is 'low', has been evaluated in a prospective randomized study. Forty-six patients met the ultrasound and oestradiol criteria for enrollment in the study, one patient participated twice. In 22 patients treatment was continued with 225 IU HMG/day and in 25 patients the HMG dose was increased to 450 IU/day. No effect of doubling the HMG dose was found on the length of the ovarian stimulation, peak oestradiol values, number of follicles > or = 11 and > or = 14 mm in diameter respectively on ultrasound on the day of HCG administration, number of cancelled cycles, number of oocytes at follicular puncture and the number of patients with < or = 3 oocytes at retrieval. It is concluded that doubling the HMG dose in the course of an IVF treatment cycle is not effective in enhancing ovarian response in low responders. This is in accordance with current theories on follicular growth, which state that follicular recruitment occurs only in the late luteal and early follicular phase of the menstrual cycle.

Comparison of results obtained with human serum and a protein solution as a supplement for in vitro fertilization culture medium.

A prospective controlled study was performed to compare the PRs obtained after use of a uniform IVF culture medium containing a pasteurized serum protein solution or patient serum. The ongoing PRs per ET in the serum and the protein solution group were 32% and 28%, respectively (not significant). Culture of supernumerary embryos showed blastocyst formation and even hatching with both supplements. The PR will not drop when this protein solution is used as a protein supplement in IVF culture medium instead of patient serum.

Vaginal disinfection with povidon iodine and the outcome of in-vitro fertilization.

In a prospective randomized study, the influence was assessed of vaginal disinfection with a 1% solution of povidon iodine (Betadine), before performing a transvaginal ultrasound-guided oocyte retrieval, on fertilization, cleavage rate and pregnancy rate. The outcome of 334 oocyte retrievals was studied. In 160 cases, Betadine was used and in the remaining 174 cases, normal saline was used. No differences in the fertilization and cleavage rates were found (fertilization 45.5% versus 47.8%, cleavage 49.8% versus 52.1% in the Betadine and normal saline groups respectively). However the pregnancy rate was significantly higher in the normal saline group (17.2% versus 30.3% clinical pregnancies per embryo transfer). No increase in infection risk occurred in the saline group.

Transcervical intrafallopian transfer of zygotes.

Reportedly, gamete intrafallopian transfer and zygote intrafallopian transfer are successful methods in assisted conception. This pilot study describes the experiences and results of a recently developed technique of vaginal transcervical intrafallopian transfer. In a group of 38 women with unexplained infertility, oocytes were retrieved. In 25 patients, pronucleate embryos were transferred to the fallopian tubes. A positive pregnancy test was reported in 8 cases. Considerations pertaining to this method and technical implications are discussed.

[Pregnancy outcome following in-vitro fertilization in the Academic Hospital Rotterdam-Dijkzigt]. / Zwangerschapsresultaten na in vitro-fertilisatie in het Academisch Ziekenhuis Rotterdam-Dijkzigt.

During the first five years of in vitro fertilisation in the University Hospital of Rotterdam, 158 pregnancies resulted in 118 deliveries of 150 babies. There were 38 clinical abortions and 2 tubal pregnancies. Transfer of multiple embryos to enhance the chance of pregnancy led to a high percentage of multiple pregnancies, 23% of all deliveries. During pregnancy the incidence of vaginal bleeding was high and the number of admissions to a hospital was increased considerably. The percentage of caesarean sections was high because of the large number of multiple pregnancies and possibly because of the 'precious' nature of the pregnancy. There was no indication of more frequent occurrence of congenital abnormalities.

Cervical pregnancy after in vitro fertilization and embryo transfer.

A case of cervical pregnancy after in vitro fertilization and embryo transfer is described. This unusual pregnancy ended at 26 weeks' gestation after hysterotomy and delivery of an 830 gm boy. We suggest that the in vitro fertilization procedure is one of the possible risk factors of cervical pregnancy.

Endocrine effects of laparoscopic ovarian electrocautery in patients with polycystic ovarian disease, resistant to clomiphene citrate.

Endocrine responses to laparoscopic ovarian electrocautery were studied in 14 patients with polycystic ovarian disease (PCOD), resistant to clomiphene citrate. Patients who did not conceive within 6 months of treatment were evaluated for up to that period. Testosterone and androstenedione levels decreased after electrocautery in a way which is comparable with the reduction in androgens after wedge resection of the ovary. Androstenedione levels tended to return to pretreatment values at 6 months; four of the five pregnancies were achieved within this period. The reduction in androgens may break the vicious circle of PCOD, and lead to normal menstrual cycles.

The influence of the interval between in vitro fertilization and embryo transfer and some other variables on treatment outcome.

This prospectively randomized study compares the outcome of 434 ETs 48 to 52 hours after insemination (day 2) and 324 ETs 72 to 76 hours after insemination (day 3). The influence of the interval between insemination and ET was assessed, as well as that of the number of embryos transferred, embryo quality, and the presence of supernumerary embryos. The mean number of embryos transferred after 2 and 3 days was equal (2.9 embryos/ET). The pregnancy rates per ET were not significantly different (21.9% versus 23.5%), but a higher percentage of viable pregnancies was observed after ET on day 3 (88.2% against 69.5% following ET on day 2). Treatment outcome was positively correlated with the number of embryos transferred and the presence of supernumerary embryos.

The value and role of plasma 17 beta-oestradiol measurements during ovarian hyperstimulation for in-vitro fertilization.

Follicular aspiration was performed in 464 hyperstimulated IVF treatment cycles in patients with severe tubal damage as the sole cause of their infertility. In 413 cycles, one to four embryos could be replaced, resulting in 102 clinical pregnancies. In 458 treatment cycles, data on plasma E2 levels were available on days -3 and -2, in 322 cycles also on days -1 and 0, day 0 being the day of follicular puncture. Although the distribution of cycles leading to clinical pregnancy within the 5-95th centile for plasma E2 levels differed from that observed outside this range, these differences were of no statistical significance. These results indicate that IVF pregnancies occur in the presence of a wide range of E2 levels, during the 3-day period preceding follicular aspiration. The importance of plasma E2 measurements for treatment policy must, therefore, be reconsidered.

Factors influencing the outcome of successive IVF treatment cycles in attaining a follicular puncture.

An analysis has been made on data from 576 cycles in 300 patients regarding the chances of various superovulation protocols attaining a puncture in successive cycles. The cumulative proportion of patients with at least one successful stimulation increased from 77% at the first attempt, to 98% at the fifth attempt. Of the 576 stimulations, 440 (76%) resulted in a puncture. Age, the number of ovaries and the reaction to superovulation induction contribute to the outcome of a cycle, the chances being lowest for older individuals with one ovary and an inadequate reaction in the first treatment cycle. Changing the treatment protocol did not improve the outcome in subsequent gonadotrophin-induced cycles, even if combined with clomiphene citrate. Reasons for cancellation did not tend to recur, although the incidence of dominance and premature stimulation was significantly higher in patients aged greater than 35 years. Age-dependent chances of success were calculated.

Ultrasonically guided percutaneous and transvaginal follicle aspiration; a comparative study.

In this study we compare the efficacy of ultrasonically guided percutaneous oocyte collection for in-vitro fertilization with ultrasonically guided transvaginal oocyte collection. Forty-seven patients were prospectively randomized into two groups. Twenty-four patients underwent percutaneous follicle aspiration and 23 patients underwent a transvaginal puncture. The number of aspirated oocytes per patient showed a statistically significant difference in the two groups: 2.5 for the percutaneous puncture versus 5.2 for the transvaginal procedure. The number of embryos per patient was 2.7 in the transvaginal puncture group versus 1.6 in the percutaneous puncture group. This difference was not statistically significant. The clinical pregnancy rate per patient was 12.5% with the percutaneous approach and 30.4% with the transvaginal technique. This difference was also not statistically significant. Since the transvaginal procedure also creates less discomfort to the patient and is less time-consuming it is concluded that this approach is preferable to the percutaneous puncture technique in obtaining oocytes for in-vitro fertilization.

The waiting-list for IVF. The motivations and expectations of women waiting for IVF treatment.

We conducted a written survey of a group of women on the IVF waiting-list at the Dijkzigt Hospital in Rotterdam. The objective of the study was to gain an insight into the motivations and expectations of the women involved. It appeared that the respondents were not very well informed on various aspects of the IVF procedure. They were also too optimistic about the chance that the treatment would be successful in their case. Even if the chance of success was very low (2%) most of the women would still choose IVF. Now that IVF exists the women wish to make use of it. They do not want to run the risk of being sorry later if they let 'the chance of having a child of their own' go by. This 'anticipated decision regret' gives IVF a strongly impelling character. Few women said that they needed a form of social guidance.

Source of plasma prorenin in early and late pregnancy: observations in a patient with primary ovarian failure.

The plasma levels of enzymatically active renin (active renin) and inactive renin (prorenin) were measured in a woman with primary ovarian failure, in whom pregnancy was established by the induction of an artificial cycle and in vitro fertilization of a donated oocyte fertilized with the sperm of her husband. The results were compared with those in nine normal pregnant women. Prepregnancy plasma active renin and prorenin levels were normal in the patient. Active renin rose 2-fold during pregnancy in both the patient and the normal pregnant women. In the first 8 weeks of pregnancy prorenin rose by 156 microU/mL in the patient, whereas it rose by 869 +/- 169 microU/mL (mean +/- SD) in the normal pregnant women. Thus, the rise in prorenin in our patient was much less than normal. Prorenin remained abnormally low throughout the pregnancy, which lasted 40 weeks. Therefore, the high prorenin levels that occur normally during pregnancy may depend on normal ovarian function. Amniotic fluid prorenin in the patient was similar to that in normal pregnant women and was 75 times higher than that in plasma. This finding suggests that prorenin production by the chorionic cells was normal in the patient and that chorionic prorenin does not contribute in any major degree to the level of prorenin in maternal plasma. Because of these findings and in light of recent evidence that the ovary secretes prorenin and produces high plasma prorenin levels in women with hyperstimulated cycles, we conclude that the ovary is the main source of the elevated plasma prorenin levels in pregnant women.

Monitoring of clomiphene citrate stimulation by means of plasma 17 beta-oestradiol determinations and ultrasonographic follicle measurements in in-vitro fertilization treatment cycles.

In 57 in-vitro fertilization (IVF) cycles stimulated with clomiphene citrate the relationship between plasma 17 beta-oestradiol (E2) and ultrasonographic measurements of follicle diameter was assessed. Under both monofollicular and multifollicular conditions a wide range in plasma E2 values was observed in the late follicular phase. No significant correlation could be established between the dimensions of the dominant preovulatory follicle and plasma E2 values, in mono-follicular or multi-follicular cycles. Pregnancies and conceptions occurred in cycles with both low and high circulating E2 levels. In pregnancy cycles a slight increase in plasma E2 values was found on the day following administration of human chorionic gonadotrophin (HCG). In conceptional cycles not leading to a clinical pregnancy, plasma E2 profiles varied considerably, whereas in cycles in which no oocytes were fertilized, plateauing or a distinct decrease occurred during this particular period. The present study suggests that the relative daily increase in plasma E2 values may be the most relevant aspect of plasma E2 monitoring.

High concentrations of immunoreactive renin, prorenin and enzymatically-active renin in human ovarian follicular fluid.

Prorenin (enzymatically inactive) and renin (active) were measured by radioimmunoassay, using monoclonal antibodies reacting either with both prorenin and renin or with renin alone, in pre-ovulatory follicular fluid (FF) from women in an in-vitro fertilization programme who were stimulated with human menopausal/human chorionic gonadotrophin. The concentration of prorenin in FF was 40 times higher than in plasma taken at the time of FF collection; renin in FF was 10 times higher. The plasma concentration of prorenin, but not of renin, in these women was higher than in non-stimulated women in the late follicular phase of the menstrual cycle. The concentration of reninsubstrate and angiotensin-converting enzyme in FF was 60% of that in plasma. Contamination of blood, which may occur at the time of FF collection, was less than 5%. Prorenin in FF was irreversibly converted into renin after adding trypsin or by endogenous serine protease, using procedures that also cause conversion of prorenin in plasma. These results support the hypothesis that the increased plasma level of prorenin in women whose ovulation is stimulated for the collection of oocytes has originated from the ovary and is under gonadotrophic control. This may also be true for the increase of plasma prorenin that has been observed in non-stimulated women during the luteal phase of the cycle and in early pregnancy.