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Four subfertile mares (at least 2 barren years) were used as donors in an embryo transfer program. The embryo recovery rate was 50%, varying between 0-100. The transfer of 9 embryos resulted in the pregnancy rate of 44%. The efficiency of embryo transfer using subfertile mares is low. In this material 20% of flushings resulted in a pregnancy.
The high rate of implantation failures in infertile patients after in vitro fertilization must be regarded as the major problem of the kind of treatment. Usually, no information on the development of the embryo can be obtained for the time between embryo replacement and rising beta-hCG levels. Own studies on the early pregnancy factor (EPF) showed a positive reaction few hours following the contact of a fertilized oocyte with the endometrial surface. Therefore, we used the EPF as a marker for the viability of the embryo in 82 patients after in vitro fertilization and embryo transfer. Within two days after embryo transfer the EPF was positive in 52 (63%) patients and negative in 30 (37%) patients. In these women the embryos may have been lost during handling or may have discontinued further development. Between day 3 and day 12 after transfer the EPF turned to negative values in 35 patients--especially between day 6 and 10. These cases must be regarded as true implantation failures. After day 12 following embryo transfer, rising beta-hCG levels could be measured in 17 women (21%), but only in 12 patients (15%) could a growing embryonic sac be detected by ultrasound. From these figures, we may conclude, that about half of the embryos are lost already during the step of embryo transfer and the other half during implantation. Therefore, more attention should be given to the handling of the embryos to increase the pregnancy rate after in vitro fertilization.
In vitro fertilization and embryo transfer (IVF) may be considered as a particular application of modern medical therapeutics linked to human reproduction. The treatment of human sterility therefore involves some fundamental human values such as life, love and death. The quality of this highly technological treatment with fast knowledge of outcome at the end of the patient's menstrual cycle has been evaluated since the early 80s. It is a typically multidisciplinary team effort involving medical doctors, biologists, laboratory technicians, nurses and clerks that is representative of modern medical practice. IVF covers much more than just embryology, as this review will explain. IVF developed in close relation with clinical and experimental research protocols, which are the major topics of this paper. The newness of the techniques used led to the necessary interactions between clinicians and biologists working on animal experimental embryology.
In vitro fertilization (IVF) and embryo transfer (ET) have resulted in the birth of nine babies, including twins. One of the twins had a congenital cardiac malformation and seven of the nine babies were girls. Labor occurred preterm in two pregnancies; and in six delivery was by cesarean section. Plasma human chorionic gonadotropin (hCG), progesterone (P), and estriol (E3) measurements and ultrasonic scans showed no obvious differences from pregnancies resulting from natural conception. Cytogenetic studies from cord blood and histologic examination of the placentas were unremarkable. The theoretic risks of pregnancy following IVF and ET are discussed. Definite conclusions cannot be drawn until a large number of babies are delivered and a long-term follow-up is completed. Initial results from the current small sample are encouraging.
In vitro fertilization (IVF) and embryo transfer (ET) were successful in 24 clomiphene citrate stimulated cycles in 22 patients. Ovarian follicular growth was monitored by ultrasound (US) and serum estradiol (E2) concentrations in order to determine the most favorable time for the induction of ovulation by administration of human chorionic gonadotropin (hCG). The day of the hCG injection was considered day 0. After an almost linear growth the mean diameter of the dominant follicle reached 19.3 +/- 2 mm on day 0. Serum E2 concentrations also increased in almost linear fashion up to a maximum of 1,037 +/- 322 pg/ml on day +1. On day 0 the mean serum E2 concentration was 862 +/- 279 pg/ml. A mean serum E2 concentration per dominant and codominant follicle of 328 +/- 100 pg/ml was found on day 0. There was no linear correlation between the follicular diameters and the serum E2-values on the same day. The time of ovum recovery was often different to the time at which ovulation would have been expected in a normal cycle.
The relationship between the ATP content of mature human oocytes and developmental potential after uterine transfer of sibling embryos was examined in 20 non-male factor in-vitro fertilization (IVF) patients matched for age, fertility history, ovarian stimulation protocol, oocyte quality and number, stage and morphology of embryos at uterine transfer. ATP content was determined for uninseminated and unfertilized oocytes for each cohort, and for embryos that developed after dispermic fertilization or which showed significant fragmentation. The effect of reduced ATP content on meiotic maturation, fertilization and preimplantation development was examined in cultured mouse oocytes treated with uncouplers of mitochondrial oxidative phosphorylation. The results demonstrated that meiotic maturation occurs in both mouse and human oocytes over a wide range of ATP contents, and that the ATP content of normal-appearing, metaphase II human oocytes can differ significantly between cohorts; however, a higher potential for continued embryogenesis and implantation in the human is associated with embryos that develop from cohorts of oocytes with ATP contents > or = 2 pmol/oocyte. The findings are discussed with respect to possible aetiologies and developmental consequences for embryonic development of different oocyte ATP contents, and the extent to which mitochondrial function may determine or influence the continued developmental capacity of embryos which appear normal and developmentally viable at the early cleavage stages.
In the decade since the birth of the first child conceived as a result of in vitro fertilization and embryo transfer much has been achieved in the field of assisted conception. Although in vitro fertilization (IVF) was successful first for the treatment of tubal disease, the indications for its use have now widened to include unexplained infertility, oligozoospermia, endometriosis and infertility due to immunological disorders. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are now used commonly for the treatment of couples where the woman has patent fallopian tubes. The huge increase in the demand for therapy using these techniques of assisted conception places considerable strain on the finances available for health care, and has led some to question the wisdom of such use of limited resources. To reduce the cost of treatment, and because repeated IVF-ET attempts may be necessary before achieving pregnancy, the initial laparoscopic approach for oocyte recovery has been largely replaced by ultrasound-guided techniques. Non-surgical embryo transfer techniques have changed little since originally described. However, where the tubes are patent, one-cell zygotes or cleavage stage embryos may be transferred into the fallopian tube (ZIFT and tubal embryo stage transfer respectively). On the other hand if the tubes are blocked, surgical embryo transfer (SET) may be performed. Most recently, some success has been achieved following the transfer of embryos into the fallopian tube by the technique of retrograde fallopian tube catheterisation.
Peak systolic velocity (PSV) of individual follicles has been correlated with oocyte recovery, fertilization rate and embryo quality [in women undergoing in-vitro fertilization (IVF) and embryo transfer]. The present study assessed the role of quantitative and qualitative indices of follicular vascularity in predicting pregnancy after IVF and embryo transfer. A total of 106 women undergoing IVF treatment for infertility who were considered to be at risk of failure (>37 years of age, history of low response to gonadotrophin stimulation, or multiple failed IVF cycles) constituted the study group. PSV was measured from the three largest follicles on both the right and left ovaries on the day of human chorionic gonadotrophin (HCG) administration using an Acuson Sequoia with a 4-8 MHz transvaginal probe. The quality of follicular flow was graded from 1 to 4 according to the amount of visible colour flow around the follicle (grade 1 when one-quarter of the follicle, grade 2 when one-half, grade 3 when three-quarters, and grade 4 when the entire follicle was surrounded by colour). Clinical pregnancies resulted in 11 (10%) of the 106 high-risk women. Women who had PSV >/= 10 cm/s in at least one follicle on the day of HCG administration more often became pregnant than those with PSV <10 cm/s (P = 0.05). All pregnancies occurred in women with grade 3 or 4 follicular blood flow. Qualitative as well as quantitative measurements of follicular flow predict pregnancy after IVF and embryo transfer.
OBJECTIVE: To study the role of serum anticardiolipin antibody in embryo implantation in an in-vitro fertilization and embryo transfer program. METHODS: 150 in vitro fertilization and embryo transfer (IVF-ET) treatment cycles from Nov. 1994 to May, 1996 were studied. Serum anticardiolipin antibody was measured by enzyme-linked immunosorbent assay (ELISA), and the clinical pregnancy outcome observed. RESULTS: Lower pregnancy rate 9.5% was found in 21 cycles of anticardiolipin antibody seropositive women compared with 26.3% in 129 cycles of anticardiolipin antibody seronegative women (P < 0.05). Patients with biochemical pregnancy and no pregnancy had seropositive anticardiolipin antibody in 20.0% and 16.2% compared with 5.6% in the patients with clinical pregnancy (P < 0.05). CONCLUSIONS: Failure of embryo implantation is associated with many factors. Our study demonstrated the serum anticardiolipin antibody in patients may play a part in embryo implantation and very early postimplantation loss.
It seems that assisted reproduction technology does not increase the rate of chromosome abnormalities, and up to now, a few cases have been reported. The case we describe here is the first one of monosomy 4q31 in a full-term liveborn after a combined GIFT-IVF procedure. Once more, this case raises the question of whether pregnancies resulting from IVF should be monitored for chromosome abnormalities or not.
BACKGROUND: It is suggested that the skill of the physician performing the embryo transfer may influence the outcome of the procedure. In this study we investigated the effects of a change in embryo transfer technique on the variability in success rates among physicians. METHODS: Retrospectively 4439 transfer cycles in which two different embryo transfer techniques were applied by seven physicians were studied. In the first 2210 cycles, transfers were performed using the 'clinical touch' method. In the following 2229 cycles, the so-called fixed distance technique was used. RESULTS: With the clinical touch method pregnancy rates differed greatly among providers, whereas after the introduction of the fixed distance technique these differences disappeared. Furthermore, the overall clinical pregnancy rate increased from 33.6 to 40.4% per transfer. Using smoothing spline curves we failed to detect a sudden rise in pregnancy rates at the time the transfer method was changed. CONCLUSIONS: The introduction of the fixed distance technique greatly reduced the variation in pregnancy rates among physicians. The overall increase in pregnancy rates after the introduction is likely to be related to the change in technique although definite proof is difficult. Both observations are suggested to be attributable to the atraumatic character of the fixed distance technique.
The outcomes of 1028 assisted reproductive technology cycles were studied retrospectively, considering two different periods of embryo transfer. In the first period, 262 cycles in women < 36 years old were studied, in which three embryos were transferred, followed by 157 cycles in women > or = 36 years, in which four embryos were transferred. In the second period, 332 cycles were evaluated in women < 36 years and 277 cycles in women > or = 36 years old, reducing the number of embryos transferred to two and three respectively. Embryos were only scored morphologically, and the best embryos were chosen for transfer. In the first period, in women < 36 years old, a clinical pregnancy rate of 55.7% was achieved, compared with 42.5% in the second period (P < 0.01). In women > or = 36 years old, the first period of embryo transfer showed a clinical pregnancy rate of 39.5%, compared with 28.5% in the second period (P < 0.01). The number of twin pregnancies in the three groups of patients in whom one to four embryos were transferred was not significantly different (24.2, 28.4, 24.8%). It is concluded that even with the biases induced by a retrospective study, the reduction in the number of embryos transferred, from three to two in women < 36 years of age, and from four to three in women > or = 36 years of age, without any selection other than pre-transfer morphological score, adversely affects the outcome of treatment, without a significant reduction in twin gestation rate. Other strategies are to be implemented in gametes and embryo selection, and patients must be aware that, even with a reduction in pregnancy rate, the goal is to achieve a high cumulative pregnancy rate, reducing the complications induced by multiple pregnancies.
This study used between-breed embryo transfer in the horse to investigate the effects of maternal size and uterine capacity on fetal growth and postnatal cardiovascular and neuroendocrine functions. Equine embryos were transferred to establish eight Thoroughbred-in-Thoroughbred (TinT), seven Pony-in-Pony (PinP), five Thoroughbred-in-Pony (TinP) and eight Pony-in-Thoroughbred (PinT), pregnancies. Maternal and foal weights and placental microscopic area were measured at birth. At 6 days of postnatal life, arterial blood pressure and heart rate were monitored and blood samples were taken for hormone analysis before, during and after a 10 min period of nitroprusside-induced hypotension. Values for maternal and foal weights and placental area at birth were larger in TinT than in PinP pregnancies (P < 0.05). PinT pregnancies resulted in larger placentae and heavier foals relative to PinP (P < 0.05). TinP had smaller placentae and lighter foals relative to TinT (P < 0.05). Growth-enhanced (PinT) foals showed elevated basal arterial blood pressure and baroreflex threshold, reduced baroreflex sensitivity, diminished plasma catecholamine responses to acute stress, and increased cortisol responsiveness to ACTH. Conversely, growth-restricted (TinP) foals showed no change in basal arterial blood pressure, baroreflex threshold or adrenocortical responsiveness to ACTH, but had enhanced baroreflex sensitivity and augmented plasma catecholamine responses to acute stress. The data show that fetal growth acceleration as well as fetal growth restriction, resulting from between-breed embryo transfer in the horse, leads to altered postnatal regulation of blood pressure and the circulating concentrations of cortisol. These findings suggest that deviations in the pattern and rate of fetal growth both above and below the normal trajectory may influence cardiovascular function in postnatal life.
We reported on the first pregnancy achieved in the Erlangen IVF program after cryopreservation and embryo transfer. After hMG stimulation in the first treatment cycle, nine oocytes were retrieved by laparoscopy from a 31-year-old woman and three embryos transferred. Five other oocytes were fertilized and developed to four- to eight-cell embryos, which were subsequently cryopreserved. Transfer of these embryos two cycles later resulted in a singleton pregnancy and the birth of a healthy girl.
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The current study was undertaken to develop a successful procedure for the nonsurgical transfer of pig embryos. A total of 663 embryos were surgically collected on Day 4 or 5 from 55 donors, of which 542 embryos of acceptable quality were nonsurgically transferred to 46 recipients. Nonsurgical recipient gilts were sedated 15 min prior to transfer with 20 mg im acepromazine maleate. A disposable insemination spirette with an attached 3-way stopcock was manipulated into the cervix of each gilt. Embryos were expelled from a tomcat catheter into the spirette, and 10 to 12 ml of Whitten's medium were used to flush embryos through the spirette into the reproductive tract. Sixteen (34.8%) recipient gilts did not return to estrus before Day 36, and 10 (21.7%) gilts farrowed with an average litter size of 4.3 +/- 0.7. Embryos were collected from an additional 20 donors and were surgically transferred to an additional 19 recipients. Surgical transfers conducted at the same time as the nonsurgical transfers resulted in 12 (63.2%) gilts farrowing and 7.1 +/- 0.6 pigs were born per litter. In conclusion, a procedure has been developed for nonsurgical transfer of swine embryos which simplifies the process of embryo transfer and which may increase the potential for utilization of embryo transfer technologies by swine producers.
The high incidence of multiple pregnancy is a major side effect of assisted reproductive technology that has recently given rise to justified criticism from different sides. The reasons for the high incidence of multiple pregnancies are discussed and a brief review is given of the steps that have been proposed to solve or at least reduce the problem. In this article, attention is particularly focused on the prevention of twin pregnancies because in terms of perinatal morbidity and associated costs, they outweigh the effect of high-order multiple pregnancies when expressed in absolute figures. The only efficacious measure to reduce the incidence of twin pregnancies is a policy of single-embryo transfer. We report on our experience with elective single-embryo transfer in good prognosis patients (age <37 years, first two in vitro fertilization (IVF) cycles and at least two embryos of high quality). About one-third of the couples meeting these criteria agreed to have a single embryo transferred, at least during their first IVF cycle. Pregnancy rates in women who had an elective single-embryo transfer (more than one high-quality embryo available) were only slightly lower than those in the group with elective double (i.e., more than two high-quality embryos available) transfer (37.9 vs. 40.0%) but the incidence of twins was 0.0 versus 27.1%. This strategy resulted in a substantial decrease of the twin pregnancy rate from 27.0 to 14.9%, without affecting the overall pregnancy rate. The conditions that are to be fulfilled before this policy can and will be applied on a large scale are discussed.