Pregnancy outcomes in in vitro fertilization cycles with serum estradiol drop prior to human chorionic gonadotropin.

OBJECTIVE: To study the effect of an unpredictable drop in serum estradiol prior to hCG administration on pregnancy outcomes in in vitro fertilization cycles. METHODS: 3653 consecutive IVF cycles from January 1, 1998 to December 31, 2000 at Brigham and Women's Hospital were reviewed, and 65 cycles in which oocyte retrieval (ER) was performed following a drop in serum estradiol (E(2)) not associated with intentional withdrawal of gonadotropins were identified. Daily gonadotropin dose was decreased at some time in 25 of these cycles, while the remaining 40 cycles did not have a reduction in gonadotropin dose. A retrospective case-control study of the respective live birth rates and pregnancy loss rates of patients with unpredictable E(2) drops in the 65 study cycles were compared to 65 age matched controls. RESULTS: Live birth rates (32% vs. 35%, p=0.72) and pregnancy loss rates (28% vs. 30%, p=0.76) were similar for all study and control groups respectively. There were no differences in live birth and pregnancy loss rates in cycles undergoing gonadotropin dose reduction (40% vs. 44%, p=0.78 and 29% vs. 39%, p=0.70) and cycles without gonadotropin dose reduction (28% vs. 30%, p=0.81 and 27% vs. 20%, p=0.72). CONCLUSIONS: In the absence of coasting, a drop in serum estradiol levels during GnRH-agonist downregulated controlled ovarian hyperstimulation for IVF prior to hCG is not associated with a decrease in live birth rates or pregnancy loss 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.

Factors associated with the formation of triploid zygotes after intracytoplasmic sperm injection.

OBJECTIVE: To determine whether clinical or laboratory factors influence development of triploid (3PN) zygotes after ICSI. DESIGN: Retrospective review. SETTING: The assisted reproductive technology program of Brigham and Women's Hospital. PATIENT(S): Patients undergoing ICSI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycles were divided into two groups: group A, cycles with one or more 3PN zygotes after ICSI, and group B, cycles with no 3PN zygotes. Age, amount of gonadotropin administered, peak estradiol levels, number of follicles, number of oocytes retrieved and injected, time between retrieval and injection, oocyte abnormalities, sperm type and motile count, percentage of diploid zygotes, and ongoing pregnancy rates were compared between groups. RESULT(S): Compared with patients in group B, those in group A received fewer ampoules of gonadotropins, had higher estradiol levels, and had more follicles on the day of hCG administration, oocytes, immature oocytes and oocytes injected and lower percentages of diploid zygotes. However, ongoing pregnancy rates did not differ between groups. CONCLUSION(S): Patients who produce 3PN zygotes after ICSI are high responders to ovarian stimulation. The appearance of such embryos is not associated with lower ongoing pregnancy rates and should not necessarily dictate alterations in ovarian stimulation protocols.

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 Women's 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.

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.

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.

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

OBJECTIVE: 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 & Women's 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 > or = 12 mm, number of follicles > or = 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, < or = 0.31 ng/ml (conversion factor to SIU, 3.180); Group II, and > 0.3 and < 1.0 ng/ml and Group III, > or = 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.

A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program.

OBJECTIVE: To compare the effect of twice (split) versus once (single) daily administration of hMG on assisted reproductive technology (ART) cycle parameters. DESIGN: A randomized clinical trial. SETTING: Hospital-based academic ART program. PATIENTS: A total of 171 patients undergoing their initial ART cycle were enrolled. All patients received one of two hMG regimens and were excluded from the study if they were receiving medications other than leuprolide acetate (LA) and hMG for ovulation induction. INTERVENTIONS: Subjects were randomized to receive an initial dose of 300 IU/d of hMG in either split-dose (i.e., 150 IU twice daily) or single-dose fashion for four successive days after down-regulation with LA. Thereafter, their daily dose was individualized, maintaining a split-or single-dose schedule. All cycles were managed in accordance with our standard ART protocols. MAIN OUTCOME MEASURES: Cancellation rate, total hMG requirements, number of days treated with hMG, E2 and P responses, oocyte yield and maturity, fertilization rate, total number of embryos, embryo quality, number of embryos transferred, implantation rate, clinical and ongoing-delivered pregnancy rates. RESULTS: Split-dose hMG administration resulted in a significantly higher implantation rate, but significantly lower normal and polyspermic fertilization rates than single-dose hMG administration. No significant differences were noted between the two dosage protocols with respect to the other outcome measures. CONCLUSIONS: Split-dose hMG administration may be associated with significantly higher implantation rates; single-dose hMG with significantly higher fertilization rates. Although our data also demonstrate a trend toward higher clinical and ongoing-delivered pregnancy rates with split-dose therapy, demonstration of a significant difference would require a multicenter trial. Based on our data, clinicians may want to consider split-dose therapy for patients with repeated implantation failures.

Dexamethasone during ovulation induction for in-vitro fertilization: a pilot study.

The purpose of the present study was to determine whether adrenal androgen suppression with dexamethasone (DEX) during ovulation induction improves the outcome of in-vitro fertilization (IVF) cycles. A total of 25 patients with serum dehydroepiandrosterone sulphate (DHEAS) concentrations > 2.5 micrograms/ml were randomized to receive either 0.5 mg DEX daily or placebo during ovulation induction with leuprolide acetate down-regulation plus human menopausal gonadotrophins (HMG). Nine patients undergoing a subsequent IVF cycle were crossed over to the other treatment group. Ovarian responsiveness and IVF outcome variables analysed included number of follicles > 12 mm in diameter, serum oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration, number of ampoules of HMG administered, number of oocytes retrieved, percentage of oocytes fertilized, number of embryos transferred, implantation rate and numbers of clinical pregnancies and live birth pregnancies. The 31 randomized IVF cycles revealed a trend towards a higher implantation rate for the placebo-treated group compared to the DEX-treated group (24 versus 10%; P = 0.07). The remainder of the IVF cycle variables revealed no statistically significant differences. In conclusion, the suppression of adrenal androgens with DEX in women with DHEAS concentrations > 2.5 micrograms/ml appears to have no beneficial effects on ovarian responsiveness or clinical or live birth pregnancy rates.

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.

Comparison of operative versus nonoperative treatment of lumbar burst fractures.

The outcomes of traumatic two- and three-column lumbar burst fracture patients treated operatively and nonoperatively were investigated with respect to treatment complications, resumption of employment, and quality of life. Data were obtained from hospital records, radiographs, and written questionnaires. Of 93 patients diagnosed with lumbar fracture between January 1987 and December 1989, 22 met the criteria for study (12 operative, ten nonoperative). Exclusion was based on single-column compression or chance fractures, neurologic compromise, and nontraumatic fractures. The patient groups had distinctly different fracture patterns based on degree of anterior column compression (ACC). Trends toward significant differences in kyphotic angulation and canal compromise were noted. There were no preoperative complications. Varying modes of external immobilization were used in both groups. One patient in each group used narcotic medications for pain at final follow-up evaluation. When comparing the operatively and nonoperatively treated lumbar burst fracture patients in this study group, no significant difference in treatment outcome was established. Nonoperative treatment remains a viable alternative to operative intervention in selected lumbar burst fracture patterns.

A self-programmable in vitro fertilization/gamete intrafallopian transfer patient database management system for MacIntosh computers.

PURPOSE: Our purpose was to develop a data processing system for a large in Vitro Fertilization/Gamete Intrafallopian Transfer (IVF/GIFT) practice which would (1) require minimal data entry time, (2) be easy to operate, (3) be simple to construct (no knowledge of procedural language or programming necessary), and (4) quickly collate and reduce data. RESULTS: A database management system was successfully constructed on an Apple MacIntosh computer which met the above criteria. The key elements of this database were its user-friendly features (MacIntosh-based system), adaptability (user was constantly able to update and revise the program as informational needs changed), and ability to perform complex searches and data analyses imposed by the individual operators. CONCLUSIONS: The software and hardware described in this report were found to be highly effective in meeting the ever-changing administrative and clinical needs of our IVF/GIFT program.

The appearance of one-pronuclear human oocytes is associated with a better ovulation-induction response and successful pregnancy outcome.

OBJECTIVE: To study the relationship between the presence of one-pronuclear oocytes in in vitro fertilization (IVF) patients and ovulation-induction response, oocyte and embryo development, and clinical outcome. DESIGN: Retrospective analysis of 535 consecutive IVF retrievals. Retrievals in which one or more oocytes exhibited one pronucleus were compared with retrievals in which no one-pronuclear oocytes (control) were observed. The following one-pronuclear versus control subgroups were also examined: leuprolide acetate/human menopausal gonadotropin (LA/hMG) ovulation inductions, high estradiol (E2) response cases, and retrievals in which a large number of oocytes (greater than or equal to 15) were recovered. SETTING: Brigham and Women's Hospital, a tertiary care, university-affiliated hospital. PATIENTS: Three hundred forty-six IVF patients were treated between January 1989 and May 1991. MAIN OUTCOME MEASURES: Parameters examined included E2 concentration and number of follicles with maximum diameter greater than or equal to 12 mm on day of human chorionic gonadotropin administration; number of total and mature oocytes retrieved; total fertilization rates; number of embryos; and percent per retrieval of embryo transfers (ETs), clinical pregnancies, and ongoing-livebirths. RESULTS: The one-pronuclear patients had higher E2 levels and larger number of follicles, yielded significantly more total and mature oocytes, had a higher overall fertilization rate, produced more embryos, and had higher ET, clinical pregnancy and ongoing-livebirth rates per retrieval than did the control patients. Analysis of the subgroup populations revealed no significant differences in the majority of the main outcome measures studied; however, the one-pronuclear patients yielded significantly more total and mature oocytes per retrieval. CONCLUSIONS: Although there was an increase in the clinical and ongoing-livebirth pregnancy rates (PRs) in one-pronuclear patients, this was probably associated with an improved ovulation-induction response in the one-pronuclear patients. They achieved significantly higher E2 levels, recruited a larger number of follicles, and yielded more oocytes and embryos per retrieval than the control patients. When only the LA/hMG, E2 greater than or equal to 1,500 pg/mL, or the greater than or equal to 15 oocytes/case retrievals were analyzed, the PRs were no longer different; however, the one-pronuclear patients still yielded significantly more total and mature oocytes per retrieval than the controls. Therefore, the appearance of one-pronuclear oocytes is probably associated with the maturation stage of the oocytes obtained and is indicative of an ovulation induction in which a large number of preovulatory, metaphase II oocytes have been recruited.

The effect of baseline complex ovarian cysts on in vitro fertilization outcome.

STUDY OBJECTIVE: To determine the effect of baseline complex ovarian cysts on controlled ovarian hyperstimulation and in vitro fertilization (IVF) outcome. DESIGN: Retrospective analysis with stratification by stimulation regimen and the presence or absence of surgically documented endometriosis. PATIENTS: Two hundred sixty-one women undergoing IVF from May 1, 1989 to December 31, 1990. MAIN OUTCOME MEASURES: The outcome measures assessed were the maximum estradiol (E2) concentration on day of human chorionic gonadotropin (hCG) administration, number of follicles with maximum diameter greater than or equal to 15 mm, number of follicles with maximum diameter greater than or equal to 12 mm, number of days to hCG administration, number of ampules of human menopausal gonadotropin (hMG) used, number of oocytes retrieved and fertilized, number of embryos transferred, and pregnancy and cycle cancellation rates. RESULTS: There were no statistical differences between cyst and noncyst groups in any of the above parameters of IVF performance. In a single subgroup, patients with endometriosis stimulated with hMG and patients with cysts had significantly lower E2 concentrations than patients without cysts. CONCLUSION: The presence of a complex cyst on a baseline ultrasound does not appear to adversely affect IVF cycle outcomes.

Mouse zygote development in culture medium without protein in the presence of ethylenediaminetetraacetic acid.

Development of zygotes from a hybrid-inbred (B6D2F1) and two random-bred (CD1 and CF1) strains of mice were compared after culture in several modifications of a simple, chemically defined medium based on Earle's Balanced Salts Solution. When cultured without the addition of protein or the chelating agent, ethylenediaminetetraacetic acid (EDTA), none of the zygotes reached the blastocyst stage. The addition of EDTA or protein significantly improved embryo development to blastocysts (p less than 0.05). The degree of improvement was dependent upon the strain of the female (85% or 91% for B6D2F1, 56% or 45% for CD1, and 19% or 28% for CF1, respectively). The addition of protein to the media in the presence of EDTA did not further improve embryo development. In all supportive conditions, zygotes from B6D2F1 females developed to blastocysts better than those from CD1 or CF1 females; embryos of the latter strain exhibited the lowest rates of development in vitro. Glycine and alanine (20 microM) partially substituted for EDTA; the decreased hybrid-inbred embryo development to blastocysts (20% and 26%, respectively) obtained in the presence of the amino acids suggested, however, that the stimulatory effect of EDTA on embryo development was other than as a source of fixed nitrogen. The rates of development observed with an alternate chelating agent, citric acid (less than or equal to 20% vs. 83% blastocysts, p less than 0.01), although better than the unsupplemented medium, were significantly less effective than EDTA-supplemented medium (83% blastocysts, p less than 0.01). The results of this study suggest that the protective effect of proteins in culture medium may be more important than their nutritive role.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Dopamine binding to the alpha receptor in pregnant rabbit myometrium.

This study evaluated in vitro binding of dopamine ligands to myometrial alpha adrenoceptors. With cell membranes from pregnant rabbits, receptor radioligand binding studies utilizing [3H] dihydroergocryptine +/- dopamine demonstrated receptor affinity (KD) = 0.75 +/- 0.10 nM (+/- SEM) and density (Bmax) = 533.2 +/- 45.2 fM/mg protein. Similar studies utilizing phentolamine or apomorphine gave essentially identical results. Competition binding studies demonstrated steriospecific butaclamol binding, along with significant binding of haloperidol, spiperone, apomorphine, and bromoergocryptine. These observations provide a mechanism for the observed uterotonic effects of dopamine.