Andrew Riddle

Heterotopic pregnancies after in vitro fertilization and embryo transfer

Seventeen cases of heterotopic pregnancies are reported among 1648 clinical pregnancies after in vitro fertilization. The high prevalence of tubal damage among IVF patients and the use of superovulation and multiple embryo transfer might predispose patients to the condition. Nine patients reported abdominal pain and vaginal bleeding, five patients did not have symptoms, and three had acute abdominal emergencies. Transvaginal ultrasonography was superior to transabdominal ultrasonography in the diagnosis of extrauterine pregnancies. The presence of an intrauterine gestation sac in a patient without symptoms should not exclude the diagnosis of a concomitant extrauterine pregnancy until the pelvis is carefully visualized. Early diagnoses of viable ectopic pregnancies before rupture abolishes mortality and morbidity and offers the chance of patient selection for conservative treatment. In two patients the extrauterine gestation sac was treated by transvaginal aspiration and injection of potassium chloride under ultrasonographic guidance. The outcome of the intrauterine pregnancy was favorable regardless of the method of treatment of the ectopic pregnancy.

An analysis of factors influencing the establishment of a clinical pregnancy in an ultrasound-based ambulatory in vitro fertilization program

In the study period (June 1984 to December 1986), 2232 cycles were stimulated in 1294 patients. Ultrasound-directed oocyte recovery (UDOR) was performed as an ambulatory procedure in 1737 (77.8%) cycles, resulting in 1375 embryos transfers (ET). Age, etiology, menstrual cycle length, number of oocytes collected, and number of embryos transferred were important determinants of the outcome. The number of attempts at in vitro fertilization did not affect the clinical pregnancy rate (CPR). In patients receiving four embryos, the CPR appeared to be highest when up to seven embryos were available for transfer. The fertilization rate in an individual cycle had a good prognostic value, the implantation rate being highest when 7 to 9 oocytes were retrieved and greater than 60% of these were fertilized. When 10 or more oocytes were collected, the implantation rate showed a progressive decline, regardless of the fertilization rate. Furthermore, multiple pregnancies failed to occur when greater than 12 oocytes were retrieved or more than eight embryos were available for transfer. These data suggest that, in excessively stimulated cycles, the quality of oocytes and embryos or uterine receptiveness may be suboptimal, and the transfer of more than four embryos is unlikely to increase the success rate.

Follicular aspiration using a syringe suction system may damage the zona pellucida

The incidence of the formation of cracks in the zona pellucida during aspiration was assessed by comparing two methods of aspirating follicular contents by suction: (a) mamuat aspiration by syringe and (b) mechanical aspiration by pump. Of 36 patients whose follicles were evcuated manually using syringes, 18 had at least one damaged cocyte. Of 38 other patients whose follicles were aspirated by pump, only one had an oocyte with a cracked zona pelluciada. Four patients had their oocytes aspirated by both syringe and pump. In all four the oocytes were intact when aspirated by the pump, but one oocyte was damaged in three of four cases when the follicles were aspirated using syringes.

Ultrasound-guided peritoneal oocyte and sperm transfer.

Peritoneal oocyte and sperm transfer (POST) was performed under ultrasound guidance and local anesthesia by the transabdominovesical route for a patient with unexplained infertility. This resulted in an intrauterine pregnancy confirmed by a raised β-human chorionic gonadotropin (hCG) level and an ultrasound scan.

Studies on the measurement and pharmacodynamics of human follicle-stimulating hormone *

The levels of immunoreactive follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), cortisol, and estradiol (E2) have been determined in serial samples of peripheral plasma from four subjects during the continuous, subcutaneous administration of Buserelin (Hoechst [UK] Ltd., Hounslow, UK) (250 micrograms/day) and after the intramuscular injection of purified, urinary FSH (Metrodin, Serono Laboratories [UK] Ltd., Welwyn Garden City, UK) (150 IU). During Buserelin administration the geometric mean levels of FSH and LH as measured by immunoradiometric assay were reduced by 87% and 37%, respectively, when compared with the corresponding values for days 1 and 2 of the menstrual cycle. After the intramuscular injection of FSH, peak levels (from 3.4 to 6.2 IU/l) occurred in peripheral plasma between 6 and 18 hours later. The levels were significantly elevated after 72 hours (P less than 0.01, Students paired t-test). There was no obvious effect of the drugs on the circadian rhythms of plasma PRL or cortisol, and no significant effect on the circulatory levels of LH or E2.

Gonadotropin- induced successful follicular development, oocyte recovery, fertilization, and cleavage of embryos in undiagnosed early pregnancy

rubber. Previous studies in this laboratory on the toxic effects of rubber components on human cell cultures (e.g., rubber plungers in syringes) (2) have demons t ra ted that the composi t ion of natural rubber can vary from time to time, and unless the rubber to which human cells are directly exposed is specifically treated and consistently tested for cytotoxicity, it should be considered a prime suspect in the event of cell inviability. In this respect we have found the use of amniotic fluid cells, which are readily available in most cytogenetic laboratories, a valuable addition to the quality control procedures due to their sensitivity to toxins which may not affect established or mouse cell lines (1,2). More extensive studies on the cytotoxic and other potential side effects Of the materials used in catheters are continuing and will be reported in due course. This preliminary report, however, provides sufficient evidence to alert those involved in IVF programs to a possible source of unexpected failure of fertilization and embryo production in patients undergoing transvesical oocyte recovery.

The sequential use of a luteinizing hormone-releasing hormone (LH-RH) agonist and human menopausal gonadotropins to stimulate folliculogenesis in patients with resistant ovaries

The diagnostic response toward the administration of a luteinizing hormone-releasing hormone (LH-RH) analogue in the early follicular phase has been used sequentially with conventional human menopausal gonadotropin (hMG) treatment in patients who had previously failed to develop multiple follicles in response to a combination of hMG and clomiphene citrate. Nine of fourteen patients (64%) showed an increase in the number of preovulatory follicles and five subjects reached oocyte recovery for the first time. Two patients (22%) became pregnant after in vitro fertilization and embryo transfer during the treatment cycle and had healthy babies. It is suggested that this treatment regimen may be advantageous in some patients with resistant ovaries.

The effect of cycle length on the outcome of in vitro fertilization

In order to study the effect of cycle length on the pregnancy rate in an in vitro fertilization and embryo transfer (IVF-ET) program, 173 consecutive patients were divided into short menstrual cycle (mode 26 days or less) and normal cycle (mode 27 days or more) groups. Patients were randomly allocated to one of two treatments, commencing ovarian stimulation with human menopausal gonadotropin (hMG) on either day 2 or day 4 of their cycle. The number of oocytes retrieved and embryos transferred did not differ significantly. The amount of hMG used and day of human chorionic gonadotrophin administration both differed significantly (P less than 0.01) between regimens but was independent of cycle length. Both the clinical pregnancy rate (30.2% versus 9.4%, P less than 0.05) and the number of cleaved embryos giving rise to gestation sacs (16% versus 3.4%, P less than 0.02) was significantly higher in patients with a normal cycle length. Mode cycle length has a significant bearing on the outcome of IVF-ET cycles.

Experience with peritoneal oocyte and sperm transfer as an outpatient-based treatment for infertility

Fifty-nine patients underwent 74 peritoneal oocyte and sperm transfer procedures. Forty-nine had previously failed treatment with inseminated frozen donor sperm and 10 had unexplained infertility. All procedures were carried out under ultrasound direction on an outpatient basis without general anesthetic by the transabdominal or vaginal route. Eighteen (24%) procedures resulted in pregnancy. Of these patients, 16 have delivered live infants (1 set of triplets, 2 twins, and 13 singletons) and 2 miscarried. Peritoneal oocyte and sperm transfer offers an outpatient-based alternative to gamete intrafallopian transfer (GIFT) for in vivo conception. It can also be used in patients scheduled for intrauterine insemination where stimulation is excessive because the number of oocytes replaced can be limited.

Studies on folliculogenesis and in vitro fertilization outcome after the administration of follicle-stimulating hormone at different times during the menstrual cycle*

The authors have undertaken a prospective, randomized clinical trial of six treatments to optimize folliculogenesis in patients prior to oocyte collection, in vitro fertilization, and embryo transfer. All treatments involved the administration of the same daily dose of follicle-stimulating hormone (FSH), but at different times during the antecedent and/or current menstrual cycle. There was a significant difference (P less than 0.01, chi-square test) between treatments in the clinical pregnancy rate/patient (19 clinical pregnancies, 67 patients). No advantages were observed for regimens that involved starting treatment during the antecedent cycle. The study was continued with the three treatments that started during the current cycle (24 clinical pregnancies, 58 patients). The most cost-effective regimen was clomiphene citrate, 100 mg/day for days 2 to 6 inclusive; FSH, 150 units/day for days 1 to 4 inclusive; and human menopausal gonadotropin, 150 units/day from day 5 until the day of human chorionic gonadotropin administration.