Initial results of an in vitro fertilization and embryo transfer program in a private health institution

Between October 1994 and the end of February 1995 115 patients were included in our programme. In these patients we monitored 141 cycles, performed 128 punctures and 100 ET. In 14 instances (9.2%) the cycle was abolished. By puncture of 1468 follicles 1370 oocytes were obtained which corresponded to a recovery rate of 93.3%. On average by aspiration 11.9 oocytes per patient were obtained. From the total number of acquired oocytes 54.6% were fertilized and 43.5% divided. Of 596 embryos 290 were transferred and the remainder was vitrified. A total of 17 clinical pregnancies were achieved, incl. 5 which terminated by abortion, the remainder proceeds. The authors are aware that they present a relatively small group during a short period of time, and thus the first results of the centre cannot be presented as a current standard. Despite this the results permit some optimism for the future and indicate a certain amount of standardization of the authors' clinical and laboratory work.     

High levels of anticardiolipin antibodies in patients with abnormal embryo morphology who attended an in vitro fertilization program

Although it is unlikely that the legislative endeavors of 1996 and 1997 relating to the health care industry will be matched in 1998, implementing regulations of the Balanced Budget Act and the Health Insurance Portability and Accountability Act will predicate the successes or shortcomings of these new laws in 1998. It is important that NPs stay in close contact with their state legislators and Medicaid officers responsible for implementing the SCHIP. NPs should also closely track efforts at the Federal level to ensure inclusion of non-physician providers in legislation that is important to NPs, such as bans on "gag" clauses--a protection that should include all health care providers.     

Ethical aspects of in vitro fertilization and embryo transfer

In vitro fertilization and embryo transfer (IVF-ET) confronts moral reflection with a wide range of concerns. Some are similar to those raised by artificial insemination such as the procurement of sperm, the goods of marriage and donor gametes. Others are unique to IVF-ET such as surrogacy, the status of the embryo and cryopreservation.     

Ultrasound in an in vitro fertilization program

Ultrasound examinations of the preovulatory follicle were performed on 39 patients in 58 consecutive spontaneous cycles in which ovum aspiration for in vitro fertilization was planned. Examinations during the follicular phase helped to indicate when patients should be admitted for intensive monitoring of urinary luteinizing hormone (LH) levels and as a means of lateralizing the side of follicular development in those patients in whom one ovary was known to be inaccessible to laparoscopic aspiration. The technique was also of value in determining whether ovulation had occurred in those patients in whom the anticipated midcycle LH surge was not detected and as a routine measure prior to laparoscopy to ensure the continuing presence of the follicle.     

In vitro fertilization/embryo transfer in unexplained infertility and minimal peritoneal endometriosis

BACKGROUND: To compare the outcome of in vitro fertilization/embryo transfer (IVF-ET) in unexplained infertility and infertility associated with minimal peritoneal endometriosis. METHODS: A retrospective analysis comparing results of stimulation, sperm characteristics, cleavage, implantation and pregnancy rates in patients with unexplained infertility and peritoneal endometriosis associated infertility. Couples with tubal infertility constituted a control group. RESULTS: In the unexplained infertility and endometriosis groups similar response to stimulation, similar sperm characteristics and cleavage rates were observed. Compared with tubal infertility lower sperm motility was seen in the unexplained infertility group. Both non tubal infertility groups had lower cleavage rate than was seen in the control group. No differences in pregnancy rate were observed, but a significantly higher implantation rate was seen in unexplained infertility compared with tubal infertility. CONCLUSIONS: Couples with unexplained infertility and infertility associated with minimal peritoneal endometriosis have similar outcomes in an IVF-ET set up. Significantly lower cleavage rates in these groups compared with tubal infertility indicate gamete defects as possible causes of infertility.     

Cornual pregnancies in patients with prior salpingectomy undergoing in vitro fertilization and embryo transfer

OBJECTIVE: To examine the frequency of cornual pregnancy in patients with prior salpingectomy undergoing IVF. DESIGN: Review. SETTING: Private fertility practice. PATIENTS: Women undergoing IVF. MAIN OUTCOME MEASURE: Cornual ectopic pregnancy. RESULTS: Of 26 ectopic pregnancies detected after ET during a 7-year period, 7 were located in the cornu or tubal stump after prior salpingectomy. CONCLUSIONS: Patients with prior salpingectomy undergoing IVF are at particular risk for cornual pregnancy.     

Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer

OBJECTIVE: To determine if an increase in plasma P occurring before hCG administration might impair the outcome of IVF-ET. DESIGN: Five hundred eighty-five IVF-ET cycles were prospectively studied for the occurrence of plasma P elevation before hCG administration. SETTING: Tertiary institution, IVF-ET program, H?pital A. Béclère. PATIENTS: Participating patients included IVF-ET candidates 23 to 42 years of age only, excluding the couples in whom a male factor was a primary or an accessory cause of infertility. MAIN OUTCOME MEASURES: To clarify the practical consequences on IVF-ET outcome of pre-hCG increases in plasma P, we studied 585 consecutive IVF-ET cycles. These were divided into two groups according to plasma P levels observed on the day of hCG administration; plasma P of 0.9 ng/mL (2.9 nmol/L) was taken as an arbitrary cutoff value. Group A included 485 IVF cycles in which plasma P was < or = 0.9 ng/mL (2.9 nmol/L); group B included the remaining 100 cycles in which plasma P was > 0.9 ng/mL (2.9 nmol/L). RESULTS: The number of mature oocytes retrieved, the oocyte cleavage rate, and the number of embryos obtained were similar in groups A and B. In contrast to this apparent similarity in oocyte quality, a decrease in pregnancy rate (PR) and a trend for a decrease in embryo implantation rate were observed in group B in comparison with group A. CONCLUSIONS: The similar fertilization and cleavage rates obtained in groups A and B suggest that pre-hCG elevation in plasma P does not lead to decreased oocyte quality. Yet the lower PR observed when plasma P rises prematurely suggests that the prolonged but discrete elevation in plasma P occurring in these cases might alter endometrium receptivity to embryo implantation.     

Limiting multiple pregnancy in in vitro fertilization/embryo transfer (IVF-ET) cycles

PURPOSE: Our purpose was to assess how the number of embryos transferred can be adjusted to limit multiple gestations. METHODS: A retrospective analysis of 535 consecutive embryo transfers for the years 1991-1993 was conducted. RESULTS: Fewer than three embryos were associated with a low pregnancy rate. Pregnancy rates were highest in women less than 35 when four or more embryos were transferred. With four or more embryos, multiple gestation pregnancy correlated with the number of high-quality embryos transferred. The risk of triplets and quadruplets was greatest for women less than 40. CONCLUSIONS: Multiple-embryo transfer carries a risk of plural gestation. The risk of multiple pregnancy cannot be eliminated without decreasing the pregnancy rate. The risk of high-order multiple pregnancy was best correlated with the number of good-quality embryos transferred. While all are at risk, patients younger than 40 were at highest risk.     

The correlation between follicular measurements, oocyte morphology, and fertilization rates in an in vitro fertilization program

OBJECTIVE: To explore the relationship between follicle size and the morphology of the oocyte-cumulus-corona complex with fertilization rates in stimulated cycles of IVF. DESIGN: Retrospective comparison of measurements and observations of 2,429 oocytes from 215 patients undergoing 324 stimulated IVF cycles. SETTING: A large hospital-based IVF program. MAIN OUTCOME MEASURES: Individual follicles were measured by ultrasound before transvaginal aspiration and the size was recorded. The oocyte-cumulus-corona complex from each follicle was examined and classified. The oocytes were checked for evidence of fertilization 17 to 22 hours after insemination. RESULTS: The fertilization rate of all oocytes regardless of morphological type revealed a positive linear correlation with increasing follicle diameter. The fertilization rates of type I oocytes was marginally higher than type II oocytes, controlling for follicle diameter; however, this difference did not achieve statistical significance. Oocytes from follicles with a mean diameter > or = 16 mm had significantly higher fertilization rates than did oocytes from follicles with a mean diameter < or = 14 mm. CONCLUSIONS: Follicle size is a better predictor of fertilization than is morphological characterization of the oocyte-cumulus-corona complex in IVF.     

The results of an in vitro fertilization program: two regimens of superovulation

Gonadotropin-releasing hormone (GnRH) agonists are increasingly used in ovarian hyperstimulation protocols in in vitro fertilization (IVF) programs. From March 1992 to June 1993, 565 patients attending our Institute underwent superovulation in 1104 IVF program cycles. Of these cycles, 650 were stimulated with clomiphene citrate and gonadotropins (human menopausal gonadotropin/hMG), and 454 with the GnRH agonist buserelin and hMG in a group of patients who had earlier failed to respond or did not conceive after clomiphene citrate/hMG stimulation. The ovarian response was similar in both groups, however, with the use of buserelin more oocytes were recovered -4.9 +/- 3.2 and 3.5 +/- 2.3 oocytes, respectively. The clinical pregnancy rate per transfer in the group of patients superovulated with buserelin/hMG was twice that of the clomiphene citrate/hMG group (21.0% vs. 10.4%). The relatively high pregnancy rate with the buserelin/hMG regimen in the group of 'poor responders' may be connected with GnRH agonist-induced pharmacological hypophysectomy and the sequelae thereof: normalization of some endocrinopathies, absence of an endogenous luteinizing hormone (LH) surge and better endometrium receptivity, oocytes and embryo quality.     

Effect of maternal age on clinical outcome in women undergoing in vitro fertilization and embryo transfer (IVF-ET)

Angiographic visualization of the hepatic vascular bed by selective angiography can be profitably complemented with the evaluation of functional portal-systemic shunting by D-sorbitol bioavailability. Seventeen patients requiring diagnostic arterial catheterization were studied: most of them had biopsy-proven liver cirrhosis. Patients were studied at rest and after overnight fasting on two subsequent days, in which a sterile pyrogen-free solution (1.5%) of D-sorbitol was administered by direct infusion (15 mg/min for 20 min) into the superior mesenteric artery and an antecubital vein, respectively. The fractional bioavailability (Fma) of D-sorbitol was calculated as the ratio between the net cumulative urinary outputs obtained after infusion through the catheter into the superior mesenteric artery and the systemic vein, respectively. A good correlation was found between the estimated fractional portal-systemic shunting, which in the present study ranged between 1.4% and 96.7%, and a suitable index scoring the clinical evidence of collateral circulation. Since the hepatic removal of D-sorbitol is not affected by sinusoidal capillarization and its hepatic extraction ratio is quite high and only slightly modified by reduction in the number or functional activity of hepatocytes, the measured Fma can be assumed as a parameter reflecting the entity of portal-systemic shunting. The test is safe and inexpensive, and appears potentially useful in several situations in which portal-systemic shunting is pathophysiologically relevant.     

Age-dependent decrease in embryo implantation rate after in vitro fertilization

OBJECTIVE: To investigate the relation between the implantation rate per embryo after replacement in IVF-ET in relation to female age. DESIGN: Retrospective study using linear and biphasic models in a multivariate analysis. SETTING: Academic tertiary care institution. INTERVENTION(S): In vitro fertilization-ET and determination of gestational sacs at 6 to 7 weeks of pregnancy buy ultrasound. MAIN OUTCOME MEASURE(S): Implantation rate as defined by the number of gestational sacs per embryo replaced. RESULT(S): Woman's age and embryo morphology were strongly related to the implantation rate, indication for IVF-ET and cycle rank number also were related significantly but less strongly. A linear model was built describing the decrease in implantation rate with age, resulting in a decrease of approximately 7%. A biphasic model was tested also and performed significantly better, resulting in a yearly decrease of > 20% after 37 years of age. CONCLUSION(S): The most important independent factors related to the ability of embryos to implant are female age and embryo morphology. The best way to describe the relation with female age is biphasic model with a discontinuity at approximately 37 years of age.     

Preimplantation genetic diagnosis increases the implantation rate in human in vitro fertilization by avoiding the transfer of chromosomally abnormal embryos

OBJECTIVE: To verify the percentage of chromosomally abnormal preimplantation embryos in patients with a poor prognosis and possibly to increase the chance of implantation by selecting chromosomally normal embryos. DESIGN: A prospective, randomized, controlled study. SETTING: In vitro fertilization program at the Reproductive Medicine Unit of the Società Italiana Studi Medicina della Riproduzione, Bologna, Italy. PATIENT(S): In a total of 28 stimulated cycles, the maternal age was > or = 38 years and/or the patient had > or = 3 previous IVF failures, factors that indicated a poor prognosis. After consent, 11 patients underwent preimplantation genetic diagnosis for aneuploidy, whereas 17 controls underwent assisted zona hatching. INTERVENTION(S): Simultaneous analysis of chromosomes X, Y, 13, 18, and 21 in a blastomere biopsied from day-3 embryos. Chromosomal analysis was performed with fluorescence in situ hybridization. Assisted zona hatching was performed on day-3 embryos from the control-group patients. MAIN OUTCOME MEASURE(S): Embryo morphology, results of fluorescence in situ hybridization, clinical pregnancies, and implantation. RESULT(S): In the study group, a total of 61 embryos were analyzed by fluorescence in situ hybridization, and 55% were chromosomally abnormal. Embryo transfer with at least one normal embryo was performed in 10 cycles. Four clinical pregnancies resulted, with a 28.0% implantation rate. In the control group, 41 embryos were transferred in 17 cycles after the assisted zona hatching procedure, yielding four clinical pregnancies and an 11.9% implantation rate. CONCLUSION(S): Infertile patients classified as having a poor prognosis have a high percentage of chromosomally abnormal embryos. The advantage of selecting and transferring embryos with normal fluorescence in situ hybridization results has an immediate impact on implantation.     

Incidence of apoptotic bodies in membrana granulosa of the patients participating in an in vitro fertilization program

Vagal primary afferent neurons have their cell bodies located in the nodose (inferior) and jugular (superior) vagal ganglia and send terminals into the nucleus tractus solitarii (NTS) which lies in the dorsomedial medulla. The presence of glutamate (Glu)-containing neurons in the rat nodose ganglion was investigated using immunohistochemistry. Glu-immunoreactivity on nodose sections was found in neuronal perikarya and nerve fibers, but not in non-neuronal elements such as Schwann cells and satellite cells. Both immunoreactive and non-immunoreactive ganglion cells were observed. The immunoreactive ganglion cells amounted to about 60% of the nodose population. No specific intraganglionic localization was observed for the non-immunoreactive cells. Immunoreactive perikarya were slightly smaller than the non-immunoreactive ones, but no relationship was found between size and staining intensities of immunoreactive neurons. The present data indicate that immunodetectable Glu is present in a large population of vagal afferent neurons. They therefore add to a growing body of evidence suggesting that Glu may be the main neurotransmitter released by vagal afferent terminals within the nucleus tractus solitarii.     

Evaluating effects of exposures on embryo viability and uterine receptivity in in vitro fertilization

We consider models for the occurrence of pregnancy following in vitro fertilization. In this clinical protocol, implantation depends on two factors: the receptivity of the uterus and the viability of at least one of the embryos transferred to the uterus. This work is motivated by the need to identify reliable bio-markers for these two factors, in order to enhance the success rate for couples undergoing this procedure. We present a general latent variable structure model for outcomes that take either one of two possible forms: as summed Bernoullis, based on an ultrasound count of gestational sacs, or as aggregated Bernoullis, based only on the outcome of a biochemical pregnancy test. We allow both uterine receptivity and embryo viability to be influenced by covariates. The proposed latent variable structure allows us to utilize the existing statistical packages to maximize an otherwise intractable likelihood function. The method is sufficiently flexible to permit any valid choice of link function. We illustrate by applying the method to a recent study of in vitro fertilization carried out in North Carolina. The number of cells at transfer is evidently a marker for embryo viability.