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PubMed1997

No evidence for a decreased fertilizing potential after in-vitro fertilization using spermatozoa from polyzoospermic men.

Polyzoospermia is generally recognized as a male factor contributing to infertility and/or recurrent abortion. Although a reduced spermatozoal fertilizing capacity is assumed to be involved, so far there is no conclusive explanation for the assumed reduced reproductive performance in these patients, and data on the fertilizing capacity of spermatozoa from polyzoospermic men are lacking. The present study therefore aimed at analysing the outcome after in-vitro fertilization (IVF)-embryo transfer in polyzoospermic patients. Retrospective analysis showed that only 0.5% out of 7863 IVF cycles were performed with spermatozoa from polyzoospermic men. The outcome of these IVF cycles shows neither a reduction in spermatozoal fertilizing capacity nor an increase in pregnancy wastage in cycles in which a pregnancy was obtained. These results may suggest a normal reproductive potential in polyzoospermic patients and therefore the question may be raised whether polyzoospermia represents a real pathological entity leading to infertility.

Embryo Transfer↗
PubMed1990

Chromosomal analysis of unfertilized oocytes and morphologically abnormal preimplantation embryos from an in vitro fertilization program.

In vitro fertilization cycles yield a low percentage of pregnancies. Eighty-five to ninety percent of the transferred embryos do not implant, and the abortion rate approaches 30%. Aneuploidy is assumed to be responsible for a major portion of this pregnancy wastage. The purpose of this study was to determine if there was any correlation between morphology and chromosomal content of unfertilized oocytes and rejected embryos. To assess the chromosomal content of oocytes and embryos, we used the method described by Tarkowski in 1966. Sixty oocytes fron 28 women, aged between 27 and 41 years, were analyzed. Sixty-seven percent were aneuploid; of these, 23.35% were hyperhaploid, 23.35% were hypohaploid, 8.35% were hyperdiploid, 3.35% were diploid, and 8.35% showed premature chromosome condensation. Of 20 preimplantation embryos analyzed, 80% were aneuploid, 10% were diploid, 5% were haploid, and 5% showed structural anomaly. Correlation was found between maternal age and aneuploidy in oocytes and between morphology and genetic balance in preimplantation embryos.

Adult↗
PubMed1993

Appraisal of in vitro fertilization.

In-vitro fertilization and embryo transfer techniques are now used all over the world (53 countries). The results of 492 of all world units were collected from national surveys and registries of different countries. Since 1985, more than 53,635 women were treated and 34,316 babies were born by 224,473 treatment cycles, followed by more than 160,518 transfer cycles. Only about 65%-75% of all resulting pregnancies attained live births. The remainder ended with spontaneous abortions (26%), or ectopic pregnancies (5.54%). The multiple pregnancy rate (22%) was higher than the normal population and contributed to higher rates of preterm deliveries and perinatal mortality. No increased incidence of chromosomal aberrations and malformations were noted during the years (2.25%). Success rates did not improve significantly within the 5-year period surveyed, in most parts of the world. The indications for treatment were broadened during the years and the procedure became a final step for diagnosis and treatment of unexplained infertility. We conclude that IVF/ET is not an empirical treatment anymore and is a relatively safe procedure, although it should be used only when properly indicated. Male infertility and infertility of unexplained origin may be accepted indications for IVF/ET. More research and centralization of treatment in fewer but large units should be established in order to improve success rates and lower the cost per live birth child. Quality control by professional or public associations should be regulated.

Abortion, Spontaneous↗
PubMed2005

[GnRH agonists versus antagonists during in vitro fertilization].

During in vitro fertilization (IVF) GnRH antagonists or agonists are used to optimize the control of organization of oocyte collection. The choice of stimulation protocol also takes into account the ovulatory, clinical, biological and ultrasound characteristics of the FIV candidate, as well as any stimulation measures already taken. Age appears to be the major predictive factor of oocyte response to stimulation and ultrasonography on the 3rd day is a predictive element of the success of oocyte collection. Determination of hormonal parameters on the 3rd day of the cycle (FSH, oestradiol, inhibin B, anti-mullerian hormone) makes it possible to refine the choice of therapy. All these elements are used to define various categories of patients in terms of response to hormonal stimulation. Agonists induce a suppression of pituitary secretion which inhibits the preovulatory LH peak and blocks natural ovulation. Nevertheless, there is an initial transient stimulating effect (flare-up) for a few days and a risk of prolonged ovarian desensitization responsible for side effects. The antagonists, administered just before the supposed ovulatory phase, provoke a rapid diminution in LH while avoiding the flare-up and prolonged ovarian desensitization. Various meta-analyses to compare both types of treatments currently suggest that agonists are superior in terms of number of oocytes produced, though the percentage of mature oocytes obtained as well as the levels of fertility are comparable whatever the type of treatment. In practice, organization of stimulation protocols using agonists is easier especially for teams working in a sequential manner. However, protocols using antagonists may be particularly useful in poor responders and are globally better tolerated.

Age Factors↗
PubMed1990

Anomalies of human oocytes from infertile women undergoing treatment by in vitro fertilization.

During in vitro fertilization treatment, three types of oocyte anomalies were observed in four infertile women. These anomalies were related to (1) failure of oocyte maturation from the germinal vesicle stage of meiosis, (2) failure of polar body formation and cleavage, and (3) absence of oocytes in otherwise mature follicular aspirates. These anomalies are considered to contribute to these patients' infertility.

Adult↗
PubMed1995

[Genetic risks of in vitro fertilization].

In-vitro fertilization (IVF) with embryo transfer is a well established therapy in infertility. With the increase of andrological problems as reasons for IVF the question of possible genetic risks is gaining additional attention. For the patients, the incidence of congenital malformations in their offspring resulting from IVF as well as the incidence of spontaneous abortions are of particular interest. In this review population genetic data of congenital malformations are compared to those found in IVF populations. On average, congenital malformations occur in 3% of all livebirths in an unselected population, whereas there were 1.5% newborns with congenital malformations reported in the IVF population. This is well within this basic background risk for congenital malformations. Bearing maternal age and especially careful follow-up of early pregnancies after IVF in mind, the rate of spontaneous abortions after IVF (21 to 27%) is also not significantly increased above the rate of 15% in the unselected general population. The introduction of microinvasive techniques into IVF has given the question of possible genetic risks for the offspring from IVF using these techniques, a great deal of topical interest. The range of indications of subzonal or intracytoplasmatic sperm injection (ICSI) includes andrological problems to a high degree which themselves could be the result of chromosomal anomalies or hereditary disorders. One example is the vas deferens aplasia in one form of CF mutations. Cytogenetic and clinical genetic evaluation should be recommended especially in cases of andrological or idiopathic sterility and infertility. Some examples of autosomal dominant syndromes in which clinical genetic evaluation and genetic counselling are advisable are listed in a summarizing table.

Abnormalities, Multiple↗
PubMed1987

Isolation of a histamine releasing factor from human embryo culture medium after in-vitro fertilization.

In-vitro fertilization (IVF) of human oocytes in our laboratories gave a percentage pregnancy rate per transfer close to 20% during 1985. Embryos were grown until the two-four cell stage and then transferred to the maternal uterus. The media from these embryo cultures were collected and subjected to chromatography on heparin-Sepharose affinity columns. The bound protein fraction contained a factor capable of inducing histamine release from sensitized basophils. The effect of this embryo-derived histamine-releasing factor (EHRF) was to induce a maximum 56 +/- 7% release of the total histamine available. This value varied between 20 and 60%, resulting from 10-30 micrograms/ml of EHRF. Since the histamine release assay performed with basophils from non-atopic donors gave no positive results, we conclude that the release was not due to a cytotoxic mechanism. This was also supported by the absence of histamine release when the assay was performed at 0 degree C, or in the presence of 2 mM EDTA, suggesting that release was dependent on an immunological interaction between EHRF and some receptor on the basophils. The immunosuppressive role of histamine is well known, and a model involving EHRF and histamine is suggested here to explain the mechanism mounted by the embryo to escape maternal immune rejection.

Culture Media↗
PubMed1988

Ovarian stimulation for in-vitro fertilization.

In-vitro fertilization (IVF) and embryo transfer has become an accepted clinical method for the treatment of sterility. Different types of ovarian stimulation have been used successfully. The therapeutic principles behind the stimulation treatment in an IVF programme are the same as those applied in the treatment of normal and hypogonadotrophic ovarian insufficiency. These include clomiphene therapy with subsequent HCG administration, combined clomiphene/HMG administration and stimulation with HMG alone, followed by HCG. A new approach to the stimulation of follicular development and oocyte maturation is the use of pure FSH and GnRH analogues. The principal indications, results, advantages and disadvantages of these different schemes of ovarian stimulation for oocyte retrieval are discussed.

Embryo Implantation↗
PubMed2005

Benefits and challenges brought by improved results from in vitro fertilization.

Abstract In vitro fertilization (IVF), in which preimplantation-stage embryos are produced after ovarian stimulation and retrieval of preovulatory oocytes, now accounts for almost 2% of all births in Australia. For clinics performing in the top quartile of national results, the chance of a live birth for a woman under 35 years from one round of egg retrieval and IVF treatment is greater than 50%, albeit still with a greater than 20% risk of twins or higher order multiple pregnancy. Similar or better live birth rates are now obtainable with the elective transfer of a single embryo at the stage of blastocyst (5-6 days in culture), a policy that if adopted for younger women can reduce the risk of twins in a clinic to less than 15%. Current developments centre around improvements to embryo culture and the testing of embryos for chromosomal normality and other genetic and epigenetic variables before transfer, made possible by licences for embryo research protocols now being issued under the Commonwealth's Research Involving Human Embryos Act 2002.

Abortion, Spontaneous↗
PubMed1994

Absence of hepatitis B virus (HBV) DNA in children born after exposure of their mothers to HBV during in vitro fertilization.

During in vitro fertilization, 22 human embryos were exposed to hepatitis B virus (HBV) in contaminated human serum present in the culture medium. All mothers experienced hepatitis B during the first trimester of pregnancy, and two had hepatitis B surface antigen and HBV DNA, as determined by PCR, at the time of delivery. No HBV DNA was found in serum or lymphocytes from the exposed 22 infants. HBV DNA was also absent from one infant at autopsy.

Culture Media↗
PubMed1997

Improving the cost-to-benefit ratio of in-vitro fertilization.

In-vitro fertilization (IVF) has been criticized for being too costly to permit ready access to needy patients, either through their own funds or through those of third party providers. European groups have managed to offer these procedures at a fraction of the cost incurred by their United States counterparts by streamlining their protocols. Accordingly, we present our methods for reducing the cost of IVF. The main modification was made by performing the IVF procedures in the clinic under i.m. analgesia, avoiding the costs of a surgery suite and anaesthesia. In addition, donor, oocyte, micromanipulation, and cryopreservation services were not offered, reducing overall personnel and equipment costs. Overall costs were reduced from customary levels of $7,000--$11,000 in the United States to $3,409 per cycle initiated, while maintaining good ongoing/delivered pregnancy rates (30.0% versus 18.6% nationally) per cycle reaching aspiration. We conclude that, through the elimination of less necessary and/or utilized procedures, IVF may be performed in a more cost-effective manner while maintaining good success rates. For the patients who desire IVF services not offered under such a system, referral to a more specialized IVF center is appropriate.

Clinical Protocols↗
PubMed1995

The role of luteinizing hormone in human follicle development and oocyte fertility: evidence from in-vitro fertilization in a woman with long-standing hypogonadotrophic hypogonadism and using recombinant human follicle stimulating hormone.

To evaluate the relative importance of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in follicular development and oocyte fertility in the human species, the use of recombinant human FSH, human menopausal gonadotrophin (HMG), and very highly purified urinary human FSH (FSH-HP) plus oestradiol valerate for ovarian stimulation and in-vitro fertilization (IVF) were compared in three cycles in a woman with isolated congenital gonadotrophin deficiency who had never been treated with ovarian stimulating agents. The total number of ampoules of gonadotrophins used was lower in the HMG treatment cycle. Ovarian response and IVF outcome in the three treatment cycles were as follows: (i) HMG cycle: normal follicular growth, normal pattern of oestradiol and inhibin through the menstrual cycle, high fertilization rate (93%); (ii) recombinant FSH cycle: normal follicular growth, low oestradiol and abnormal inhibin, finally poor rate of fertilization (28%); (iii) FSH-HP plus oestradiol valerate cycle: normal follicular growth, normal pattern of inhibin and poor fertilization rate (27%). Luteal plasma progesterone concentrations were much higher in the HMG treatment cycle. This case shows that FSH is the only factor required in order to induce follicular growth in the human, although LH or a product derived from its action may assist in order to achieve full follicular maturity and oocytes capable of fertilization. Though oestradiol might have a mediatory role in the process of follicular maturation, our results favour a direct primary role of LH in complete maturation of the follicle.

Adult↗
PubMed1992

Natural oocyte retrieval with intravaginal fertilization: a simplified approach to in vitro fertilization.

To simplify in vitro fertilization (IVF), we have combined natural-cycle oocyte retrieval with intravaginal fertilization. Our subjects ranged in age from 28-40 years and were monitored by ultrasound and steroid hormone levels. Oocyte retrieval was carried out under vaginal ultrasound-guided aspiration 32-36 hours after the onset of the LH surge. The oocyte was identified and placed in a sealed capsule containing culture media and sperm. The capsule, in a sealed cryoflex envelope, was placed in the woman's vagina and removed 42-48 hours later. The embryo was then isolated and transferred to the woman's uterus. Fifty-one retrieval cycles were attempted in 45 patients. At least one oocyte was retrieved in 88% of cycles, and fertilization was achieved in 84% of oocytes. Of the five clinical pregnancies (10%), four have delivered and one is ongoing. The cost of this procedure is approximately one-third that of standard IVF. The advantages of our method are the elimination of the use of gonadotropins, the simplicity of monitoring and oocyte retrieval, and the lack of need for expensive laboratory equipment. Natural oocyte retrieval with intravaginal fertilization may prove appropriate for those women requiring IVF who fear multiple pregnancies, have side effects from controlled ovarian hyperstimulation, or cannot afford standard IVF.

Adult↗
PubMed1996

The indirect immunobead test for seminal antisperm antibodies and fertilization rates at in-vitro fertilization.

A series of 183 patients with positive indirect immunobead tests on semen was studied to determine the correlation in semen between specific antibody types, binding sites, antibody concentration, and fertilizing ability. IgM was present in only 44 ejaculates and was present in sufficient quantity to cause significant binding to immunobeads (i.e. >20% of motile donor spermatozoa) in only three of them. There was no correlation between the percentages of motile donor spermatozoa that bound IgA and IgG immunobeads but the two classes of beads generally bound to the same region of the spermatozoa. A total of 63 couples went on to attempt in-vitro fertilization (IVF) treatment, all with mature eggs recovered. Of these mature eggs, 44% were fertilized and cleaved normally in comparison to 68% in a group of patients with tubal disease. Fertilization rates in individuals followed a bimodal distribution with a substantial number of couples experiencing zero or very poor rates (0-20%), the mode for the remainder lying between 60 and 80%. The fertilization rate tended to decrease as the amount of antibody increased. The percentage of donor spermatozoa that bound to immunobeads, taken as the greater of IgA and IgG, was selected by logistic regression as a significant predictor of poor fertilization (rate <=25%). The predictive power of the equation was improved by including the motile normal sperm concentration but the equation could only account for a small proportion of the total variation in fertilization rate. The presence of antibodies to the sperm head was highly correlated with the antibody concentration but was not selected as a predictor of fertilization. We conclude that the nature of the antigen against which the seminal antisperm antibody is directed may be as important as the antibody concentration in affecting sperm function. There seems to be little practical value in measuring IgM in seminal plasma.

Adult↗
PubMed1992

The use of ejaculated boar semen after freezing in 2 or 6% glucerol for in vitro fertilization of porcine oocytes matured in vitro.

Two concentrations of glycerol in a freezing diluent were tested with respect to the in vitro fertilizing capacity of frozen-thawed boar spermatozoa which, before exposure to oocytes, were subjected to 3 methods of fractionation. These were 1) the upper fraction, 2) the swim-up and 3) percoll gradinet-centrifugation. The highest proportions of motile spermatozoa were obtained by the swim-up procedure, while acrosomal integrity was best preserved by the upper fraction procedure. Raising the glycerol concentration from 2 to 6% (v/v) during freezing decreased the proportion of spermatozoa with a normal apical ridge. Spermatozoa separated by the upper fraction method showed the greatest penetration of oocytes and produced the highest incidence of polyspermy. The glycerol level affected penetration and polyspermy only with spermatozoa separated in a percoll gradient, where the higher level of glycerol increased oocytes penetration and polyspermy. Pronuclei formation was influenced by the separation procedure and by the glycerol concentration in the freezing diluent. The results indicate that frozen boar semen can be used for in vitro fertilization more successfully than fresh semen since penetration by frozen upper fraction spermatozoa was similar to, the degree of polyspermy was lower, and the formation of two pronuclei was greater (P<0.01) than in oocytes exposed to fresh semen.

Journal Article↗
PubMed1995

The creation of mouse models for human diseases associated with reproductive disturbances by in vitro fertilization and embryo transfer.

The induction of ovulation by hormone treatment, preparation of fertilized eggs by in vitro fertilization and recovery of offspring by embryo transfer were studied in five strains of mutant mice: C57BL/6-dy/dy progressive muscular dystrophy model, C57BL/6-ob/ob obesity model, and BALB/c-rl/rl, BALB/c- shi/shi and C57BL/6-mld/mld motor ataxia models. The homozygotes of these mutant mice are all affected with the disease about 2 weeks after birth, followed by reproductive disturbances. Ovulation could be induced by injection with PMSG-hCG in the females. Sperm was obtained from the cauda epididymis of males and used for in vitro fertilization. The success rate of the in vitro fertilization was as low as 71.6% in C57BL/6-dy/dy mice, but was over 85% in the other strains. When 2-cell embryos obtained by in vitro fertilization were transferred to the oviducts of pseudopregnant recipients, offspring were obtained from 39.2-57.7% of the transferred embryos. These offspring developed the expected diseases about 2 weeks after birth, and it was confirmed that the disease characters were reliably reproduced. These results demonstrate that the experimental system of in vitro fertilization and embryo transfer enables production of the offspring homozygous for a mutant gene and use of them for experiments before the onset of the disease which has been impossible.

Animals↗
PubMed1999

Effect of in-utero diethylstilboestrol exposure on human oocyte quality and fertilization in a programme of in-vitro fertilization.

Genital tract abnormalities and adverse pregnancy outcome are well known in women exposed in utero to diethylstilboestrol (DES). Data about adverse reproductive performance in women exposed to DES have been published, including controversial reports of menstrual dysfunction, poor responses after ovarian stimulation, oocyte maturation and fertilization abnormalities. We compared oocyte quality, in-vitro fertilization results and embryo quality for women exposed in utero to DES with a control group. Between 1989 and 1996, 56 DES-exposed women who had 125 in-vitro fertilization (IVF) attempts were retrospectively compared to a control group of 45 women with tubal disease, who underwent 73 IVF attempts. Couples suffering from male infertility were excluded. The parameters compared were oocyte quality (maturation abnormalities, immature oocyte, mature oocyte), fertilization and cleavage rate (per treated and metaphase II oocytes), and embryo quality (number and grade). We found no significant difference in oocyte maturational status, fertilization rates, cleavage rates, embryo quality and development between DES-exposed subjects and control subjects. These results suggest that in-utero exposure to DES has no significant influence on oocyte quality and fertilization ability as judged during IVF attempts.

Adult↗
PubMed1982

[Evaluation of the fertility of human sperm by interspecies (man-hamster) in vitro fertilization].

An "in vitro" fertilization test employing zona-free hamster eggs was used to analyse human spermatozoal fertilizing ability. Sperms from 28 men (group 1) whose wives were candidates for "in vitro" fertilization and embryo transfer, and from 5 men belonging to infertile couples (group 2), were evaluated for their ability to penetrate and decondense in zona-free hamster ova. All men had spermiograms in the normal range. A total of 529 eggs were inseminated with spermatozoa from group 1 and the fertilization rate was found to range from 8% to 100% with an average of 57.5%. Of the 130 ova tested with sperm from group 2 individuals, only one showed any evidence of penetration. The fertilization rate and the degree of polyspermy failed to show a significant correlation with sperm concentration in the ejaculate or motility. This cross-species system is a useful additional test to the classic spermiogram and may have a potential value as a diagnostic tool in evaluating human spermatozoal fertilizing capacity, avoiding the ethical and logistical problems associated with fertilization of human eggs "in vitro".

Animals↗