Current state and future of IVF.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Trounson.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
During February 1979 to December 1983, 831 infertile couples were treated by in vitro fertilisation and embryo transfer. The problems they faced included deciding on the number of oocytes to be collected at laparoscopy, the numbers to be donated or fertilised, the numbers of embryos to be transferred and frozen, and whether abnormal embryos should be used for research or discarded. The 831 patients received a total of 1530 treatment cycles. Of the 763 patients for whom complete data were available, 136 (17.8%) became pregnant. The rate of pregnancy, however, increased dramatically from 7.4% when only one embryo was transferred to 21.1% and 28.1% when two and three embryos were transferred, respectively. The chance of multiple pregnancy also increased with the number of embryos transferred, but the risk (2% for twins) was far outweighed by the relatively poor result after transferring a single embryo. Out of 40 embryos freeze-thawed, 23 survived thawing and were transferred; of these, 4 (17%) resulted in pregnancy. Thirty four transfers of donor oocyte embryos also resulted in four pregnancies (12%), but two of these ended in abortion. Neither microscopy nor any other available test can determine the potential of an oocyte to result in pregnancy, so that discarding oocytes that may look abnormal simply reduces the chances of conception--both for the patient and for any prospective recipient of donor oocyte embryos. In any case, abnormal embryos tend to die when growth is allowed to continue in vitro. Probably all oocytes harvested from a patient should be inseminated and the utilisation of the embryos decided once the number developed is known.
Studies on in vitro fertilization were begun at Monash University in 1970. A review is presented summarizing developments since then, culminating in pregnancy rates of 18% in 1980, 22% in 1981, and 19% in 1982.
Eighteen two- to four-cell embryos, cultured in vitro for 32-65 hr after insemination, were examined by transmission electron microscopy to assess their normality and developmental potential. These stages are now being widely used for embryo transfer in in vitro fertilization clinics. They were obtained by inseminating preovulatory oocytes aspirated at laparoscopy, with or without ovarian stimulation, by methods which have yielded normal pregnancies. The organization of seven embryos was apparently normal and their blastomeres had cellular organelles usually present in fertilized ova. Details of their ultrastructure including subtle changes observed on prolonged culture are described. Other embryos showed some normal and obvious abnormal features, such as partial fragmentation and multinucleated blastomeres, or evidence of degeneration.
The effects of supplementing culture medium with protein for the culture of mouse embryos from two cells to blastocysts were examined in vitro. The proportion of embryos developing was affected by the type of protein and concentration. The highest rates were obtained in protein-free medium, fetal calf serum, and A Grade bovine serum albumin at all concentrations tested (2-16 mg/ml). Reduced rates of embryo development were observed in proteins of human origin, particularly at the highest concentrations tested. Purification of human and bovine serum albumin resulted in a marked reduction of embryo development. Significantly more normal fetuses were found in pregnant mice receiving transferred embryos grown in protein free-medium than in medium containing fetal calf serum. It is concluded that protein supplementation of culture medium may adversely affect embryo development and viability. These observations could have important implications for human in vitro fertilization.
The reinsemination of human oocytes that failed to show any evidence of fertilization 12 to 14 hours after insemination was examined to determine whether this would increase success of in vitro fertilization or be of use in determining the fertilizing capacity of the husband's spermatozoa. Reinsemination with spermatozoa of a donor of known fertility resulted in a significantly higher fertilization rate than reinsemination with the husband's spermatozoa. However, the rate of the spontaneously delayed fertilization in oocytes that were not reinseminated was not significantly different from fertilization rates following reinsemination with either the donor's or the husband's spermatozoa. One pregnancy that miscarried at 12 weeks' gestation was obtained from reinseminated oocytes, and none was obtained from oocytes that were spontaneously delayed in fertilization. It is concluded that at present neither reinsemination nor embryo replacement in utero of embryos resulting from delayed fertilization is useful for human in vitro fertilization.
The aetiology of idiopathic infertility largely appears to lie within the female genital tract. The causes may be related to psychological, hormonal or biological factors that could influence sexual behaviour or function of the cervix, uterus, tubes or ovaries. Carefully controlled prospective studies are needed to evaluate diagnoses and therapy. Management of cases of long-standing idiopathic infertility in an IVF programme is indicated if the pregnancy rates of the programme are greater than 10%, as it will aid in both diagnosing the underlying cause as well as offering a significantly higher chance of pregnancy than either expectancy or other treatments.
The use of donor eggs and embryos is indicated in those infertility cases where the recipient's eggs are either absent, unavailable or inappropriate for in vitro fertilization (IVF) and embryo transfer (ET) programmes. Donor eggs may be fertilized by either the sperm of the recipient's husband (donor egg programme) or by donor sperm (donor embryo programme), in vitro or in vivo and may be transferred as either fresh or frozen-thawed embryos. Human pregnancies and livebirths have recently been reported following the donation of embryos fertilized both in vitro and in vivo. The development of this new technique will allow the achievement of normal pregnancy in infertile women who hitherto had no possible chance of pregnancy.
In vitro fertilisation after stimulation of the ovulatory cycle has led to successful pregnancy. If more oocytes are recovered than are needed they may be left unfertilised, preserved, or donated to a recipient couple from whom oocytes cannot be obtained. A case of human pregnancy initiated by transfer of a donated embryo fertilised in vitro is reported. The donor was a 42 year old woman with primary infertility from whom six follicles were aspirated after stimulation of the ovulatory cycle. The recipient was a 38 year old infertile woman who had undergone several unsuccessful attempts for artificial insemination from a donor. Five oocytes were recovered from the donor's six follicles, four of which were inseminated with spermatozoa of the donor's husband and the fifth with a frozen sample of semen. Three of the four embryos fertilised by her husband were returned to the donor and the fifth was transferred to the recipient. No pregnancy was recorded in the donor, but pregnancy was confirmed in the recipient, though spontaneous abortion occurred after 10 weeks. This case will give useful information for further study of in vitro fertilisation, but also raises many ethical issues.
The ultrasound results in 141 patients through 203 cycles stimulated with clomiphene citrate prior to oocyte collection and in vitro fertilization are analyzed. A wide range in the size and number of follicles was seen. Bivariate analysis of the size of the largest follicle, compared with the time of the spontaneous luteinizing hormone (LH) surge, has shown a highly significant correlation (r = 0.720; P less than 0.001) between these two variables, but the accuracy of prediction of the LH surge in a specific cycle, as expressed by the standard error of estimate, was 34.3 hours. As an isolated observation, ultrasound results are no better than the menstrual history in predicting the time of the LH surge in stimulated cycles. Multiparameter assessment of follicular development is required.
Explore the source record for details and available documents.
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 a program of human in vitro fertilization (IVF), the results of 204 attempted intracervical embryo transfers (ETs), using a variety of catheters in three trials over 18 months, have been analyzed for the ease of transfer and pregnancy rate. In nulliparous patients, transfers were more difficult than in multiparous patients; and a closed-end Teflon catheter was found to be more easily passed through the smaller cervical canal than an open-end catheter. The overall pregnancy rate was 17% (March 1980 to August 1981) and was not related to catheter type, although when chemical pregnancies were excluded, it was found that transfers using open-end catheters were more successful. The transfer procedure developed finally for routine use incorporates a consideration of these results.
The technique of in vitro fertilization (IVF) is now established as a successful clinical procedure for the treatment of infertility in at least two world centres (Cambridge, England; Melbourne, Australia). These two centres are achieving a success rate of establishing pregnancy in more than 20% of patients undergoing attempted oocyte recovery. As a consequence of the independent success of these two groups, there is a rapid proliferation of clinics developing experience with IVF and within a short time there will be many successful and viable IVF clinics operating throughout the world. Already pregnancies are being reported in the USA, France and other clinics in Australia and England. Although much of the initial work towards a viable IVF procedure has been done, application of the procedure for treatment of infertility and the development of many other possible areas for exploration as a result of successful IVF will keep innovative researchers and clinicians busy for a very long time.
An analysis of nine pregnancies resulting from in vitro fertilization and embryo transfer was made in order to identify factors common to all of the pregnancies. These factors included clomiphene stimulation; general anesthesia for laparoscopy; identification of large follicles (greater than 8 ml) and a mature oocyte; preincubation of the oocyte for 4.7 to 6.5 hours in vitro before insemination; insemination with 0.8 to 1.3 x 10(6) fresh spermatozoa from fertile samples; transfer to the uterus of two-, four-, and eight-cell embryos, 38 to 50 hours after insemination; and uncomplicated uterine transfers of embryos. It was difficult to determine whether these factors are causal or coincidental in the attainment of successful pregnancies. The detailed analysis was useful in demonstrating factors which did not prevent the establishment of pregnancy by in vitro fertilization and embryo transfer. These factors included a variety of causes of infertility, including idiopathic and male infertility; age of the infertile woman over 35 years; the presence of T-mycoplasma in the genital tract; the use of human chorionic gonadotropin; a variety of agents used for general anesthesia; the use of carbon dioxide to induce pneumoperitoneum; a delay of up to 50 minutes in the interval between the induction of general anesthesia and oocyte recovery; the use of antiprostaglandins at the time of embryo transfer; and a brown discharge from the vagina following embryo transfer.
IVF may be used for diagnostic or therapeutic reasons. In patients with idiopathic infertility IVF may distinguish between defects in the spermatozoa or oocyte. At present IVF and ET offers patients with either tubal or idiopathic infertility only a small chance of becoming pregnant (4 to 13 per cent). General application of IVF and ET will be determined by future success rates and incidence of fetal malformation. Selection, preparation and management of patients requires a specialized team, meticulous attention to detail and intense work. The results at four steps in the procedure can be analysed: the rate of oocyte collection is 85 to 90 per cent, the rate of fertilization, 80 to 90 per cent, the rate of embryo development, 50 to 70 per cent, and the pregnancy rate per laparoscopy, 4 to 13 per cent. The factors determining success are not known. The collection of mature oocytes, the use of particular culture media and ease of embryo transfer are important. There are advantages in using clomiphene citrate HCG stimulation rather than the natural cycle. Pregnancy has occurred despite factors thought to be deleterious to IVF: general anaesthesia, carbon dioxide pneumoperitoneum, prolonged anaesthesia before oocyte collection and bleeding before or after ET. Ethical and legal aspects of IVF and ET require consideration by the community, legal profession and religious groups, and suitable guidelines need to be established for scientists and doctors.
Explore the source record for details and available documents.