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PubMed1990

Improved methods for preparation of culture media for in-vitro fertilization and gamete intra-fallopian transfer.

A new method for preparation of culture media for IVF-ET and GIFT was developed which eliminated the requirement for volumetrics and glassware. Water weight was used instead of volumetrics for preparation of media. Media prepared by the volumetric and water weight methods were compared for (i) preparation time, (ii) pH, (iii) osmolarity and (iv) the percentage of two-cell murine embryos developing to blastocysts. The time required for preparation of media was significantly less for the water weight method. Following equilibration with 5% CO2, no differences were observed between the two methods for pH, osmolarity or development of embryos to the blastocyst stage. Time for media preparation and osmolarity was less variable among preparation days for the water weight method. These results suggest that media can be prepared more efficiently and precisely with the water weight method than with the standard volumetric method used by most IVF laboratories. The former method eliminates considerable technician time which must be devoted to proper cleaning/sterilization of volumetrics and the possibility of media contamination by residual substances remaining on volumetrics following improper cleaning.

Animals↗

PubMed1994

Relationship of initial chorionic sac diameter to abortion and abortus karyotype based on new growth curves for the 16th to 49th post-ovulation day.

In order to determine whether initial chorionic sac diameter is related to subsequent abortion, abortus karyotype, or birth weight and length, chorionic sac diameter was prospectively measured by transvaginal ultrasound in 700 singleton pregnancies before post-ovulation day 31, the latest day cardiac activity becomes detectable in normal pregnancy. Results were compared to values for the 10th to the 90th centiles, determined from 227 measurements of in-vitro fertilization and gamete intra-Fallopian transfer pregnancies. The abortion rate was 23.9% [95% confidence interval (CI) 19.2%, 28.6%] when initial chorionic sac diameter was below the 50th centile, compared to 6.9% (95% CI 4.9%, 9.4%) when equal to or above the 50th centile. Chorionic sac diameter was below the 50th centile in all anembryonic abortions and in 62% of embryonic abortions. Triploidy, trisomy 47 + 16, or trisomy 16 and the presence of satellite bodies on chromosome 22 were the only abortus karyotypes significantly associated with small chorionic sac diameter. Initial chorionic sac diameter was not associated with birth weight or length. We conclude that chorionic sac diameter is decreased in anembryonic and embryonic abortion and that normal pregnancy outcome may be expected in 90-95% of pregnancies in which initial chorionic sac diameter is equal to or above average.

Abortion, Spontaneous↗

PubMed1994

Multiple pregnancy induction and selective fetal reduction in high genetic risk couples.

Couples at risk for an inherited disorder often have several pregnancy interruptions because of affected fetuses and difficulty in achieving their desired family. We evaluated the efficiency and acceptability of selective fetal reduction after chorionic villus sampling (CVS) of multiple pregnancy induced by ovarian stimulation and gamete intra-Fallopian transfer (GIFT). This approach has been offered to nine patients at risk of Mendelian diseases and one patient carrier of reciprocal translocation. The acceptance has been very high (90%). One patient at risk of an autosomic recessive disease opted for artificial donor insemination, one conceived spontaneously, and one was a poor responder to ovarian stimulation. Seven patients actually underwent a single GIFT procedure with six achieving pregnancy (86%), all but two being a multiple pregnancy (67%). All pregnancies concluded uneventfully at term and newborns were alive and healthy. Prenatal diagnosis, including fetal karyotyping in all cases, was performed at 8.5-11.5 weeks of gestation and confirmed either on amniotic fluid aspirated at reduction or at birth. The number of fetuses was reduced to one or two because the genetic disease was present and/or to reduce the risk of premature delivery and improve the likelihood of successful pregnancy. The new approach seems to be highly effective and might be considered a practical and useful alternative to preimplantation genetic diagnosis.

Abortion, Induced↗

PubMed1992

[A randomized prospective study comparing supplementation of the luteal phase and early pregnancy by natural progesterone administered by intramuscular or vaginal route].

Deficiency in the luteal phase has been shown during stimulated cycles using a protocol involving a GnRH agonist. The authors undertook a randomised prospective trial of supplementation by progesterone of the luteal phase and of early pregnancy in two hundred and seventy two patients requiring fertilisation in vitro (FIV), gamete inter-fallopian transfer (GIFT) or zygote inter-fallopian transfer (ZIFT). Either progesterone in solution in oil (50 mg/day) administered by intramuscular injection or micronized progesterone administered intra-vaginally (600 mg/d) were used as support for the luteal phase. Administration of progesterone in association with estradiol valerate was started on the day prior to oocyte puncture and was continued until the 12th week of pregnancy. The implantation rate was very close to the threshold of significance (P = 0.07) in favour of the patients given vaginal progesterone. There was a higher rate of clinical pregnancies (33.6 versus 26.7 p. cent) in the latter group, though this was not significant. While plasma progesterone (Pg) levels were lower in patients using vaginal progesterone, the abortion rate during the first three months was lower in this group (P < 0.05). Micronized progesterone administered vaginally was well tolerated by all patients. During stimulated cycles, notably by GnRHa, it thus proved to be more effective than Pg administered by intramuscular injection with regard to implantation and abortion rates.

Administration, Intravaginal↗

PubMed1995

Ultrasonographic appearance of polycystic ovaries is associated with exaggerated ovarian androgen and oestradiol responses to gonadotrophin-releasing hormone agonist in women undergoing assisted reproduction treatment.

While no single biochemical test is diagnostic of polycystic ovary syndrome (PCOS), most patients show a characteristic ovarian ultrasonographic appearance. It has been proposed that a dysfunction of cytochrome P-450c17 alpha in PCOS leads to an increased 17-hydroxyprogesterone (17-OHP) response to a gonadotrophin-releasing hormone (GnRH) agonist-induced gonadotrophin rise. We postulated that this abnormality of steroid metabolism might influence the ovarian response during assisted reproduction treatment. We investigated 106 patients undergoing a short 'boost' stimulation regimen for assisted reproduction treatment, including in-vitro fertilization and gamete intra-Fallopian transfers. The ovarian ultrasound pattern was correlated with serum testosterone, 17-OHP, androstenedione and oestradiol responses, and with the clinical outcome. Polycystic ovaries, defined ultrasonographically as the presence of > or = 10 follicles between 2 and 10 mm diameter in either ovary, were found in 48% of the whole study population. Dexamethasone was given to suppress adrenal androgen secretion. Functional ovarian hyperandrogenism (FOH) was defined as serum testosterone > 0.5 nmol/l after dexamethasone. There was a significantly (P < 0.001) higher prevalence of FOH in patients with polycystic ovaries (23%) compared with normal ovaries (7%). Patients with polycystic ovaries had approximately double the 17-OHP, androstenedione and oestradiol responses to a GnRH agonist as patients with non-polycystic ovaries. Exaggerated 17-OHP and oestradiol responses to GnRH agonist were found in 89% of patients with clinically diagnosed PCOS. The number of oocytes retrieved was positively correlated (r = 0.51, P < 0.001) with the oestradiol responses in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

PubMed1992

Serum inhibin levels in gonadotrophin stimulated in-vitro fertilization/gamete intra-fallopian transfer cycles.

Serum inhibin concentrations of 64 cycles of in-vitro fertilization--embryo transfer (IVF-ET) or gamete intra-Fallopian transfer (GIFT) have been analysed retrospectively. No significant difference was observed in serum inhibin levels of cycles stimulated with buserelin and human menopausal gonadotrophin (HMG) or HMG alone. During the late follicular phase, serum inhibin was higher in cycles resulting in pregnancy than in cycles without a pregnancy (peak values on day +1: 8.3 versus 6.4 IU/ml, respectively). The same difference was found between stimulation cycles resulting in a viable or a non-viable pregnancy (peak values on day +1: 8.3 versus 7.5 IU/ml). However, these differences were not significant. During the early luteal phase, serum inhibin values were similar in these groups of patients. Our results indicate that the use of the gonadotrophin-releasing hormone (GnRH) analogue buserelin, in combination with HMG, for ovarian stimulation does not affect inhibin production by granulosa cells in vivo. The late follicular and early luteal concentrations of serum inhibin have to be considered unsuitable as predictors in IVF/GIFT cycles with respect to pregnancy and pregnancy outcome.

Adult↗

PubMed1994

The obstetric outcome of singleton pregnancies following in-vitro fertilization/gamete intra-fallopian transfer.

The present study compares 465 singleton live deliveries from in-vitro fertilization/gamete intra-Fallopian transfer (IVF/GIFT) pregnancies with a large control population to evaluate the incidence of pre-term delivery and small for gestational age (SGA) or very small for gestation age (VSGA) babies resulting from IVF/GIFT pregnancies. Overall the incidence of SGA or VSGA from an IVF/GIFT pregnancy is higher than from the normal obstetric population (SGA odds ratio 1.76, 95% confidence interval (CI): 1.38-2.25 and VSGA odds ratio 1.61, 95% CI: 1.05-2.46) particularly among primiparous women (SGA odds ratio 1.99, 95% CI: 1.25-3.16 and VSGA odds ratio 1.97, 95% CI: 1.49-2.62). After stratifying by the cause of infertility, only women with unexplained infertility had a significantly higher proportion of SGA/VSGA babies. There was a significantly higher incidence of pre-term deliveries among the young primiparae (odds ratio 5.02, 95% CI: 3.09-8.13). Thus the excess risk of delivering a SGA/VSGA baby and pre-term delivery from an IVF/GIFT pregnancy seems to be largely confined to women with unexplained infertility and young primiparae.

Adult↗

PubMed2001

Ultrastructural evaluation of recurrent and in-vitro maturation resistant metaphase I arrested oocytes.

An infertile couple whose female partner showed recurrent retrieval of immature metaphase I (MI) oocytes that were resistant to in-vitro maturation, was studied. Four spermiograms revealed teratozoospermia. Consistent non-fertilization and negative pregnancy outcomes were obtained after intrauterine insemination, gamete intra-Fallopian transfer and IVF. Two intracytoplasmic sperm injection (ICSI) cycles were finally performed. All oocytes (n = 17) in both cycles were arrested at MI and failed to mature after 48 h culture. ICSI also resulted in total non-fertilization. In the last cycle, two oocytes were analysed by transmission electron microscopy and showed almost identical results. All organelles showed normal characteristics of an MI oocyte. The main abnormality found was related to the MI spindle, with absence of microtubules and dispersion of the female chromosomes. Minor abnormalities were observed (immature fibrous appearance of the zona pellucida; the presence of small vesicle aggregates which formed a foam-like body). The injected sperm nucleus was arrested in the middle of the chromatin decondensation process, with no visible nuclear envelope reformation. Normal disruption of sperm acrosomal and flagellar components were observed. Only a partial cortical reaction was observed. This represents the first documented case of developmental arrest due to complete absence of spindle formation in association with an otherwise mature ooplasm.

Acrosome↗

PubMed1990

Possibilities and limitations of techniques of assisted reproduction for the treatment of male infertility.

Since relatively few spermatozoa are needed for oocyte fertilization during gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF), these methods have been applied in couples with infertility due to male causes. Forty-six couples with male factor infertility were enrolled in this study and results were compared with those attained in 48 couples treated with the same techniques for other than male causes. Overall, GIFT resulted in 26% ongoing pregnancies. GIFT seems to be particularly successful when the sperm concentration is 20 x 10(6)/ml or more, but sperm motility and/or morphology are poor. Nine pregnancies occurred out of 26 GIFT cycles in 18 cases selected on this basis. The ongoing pregnancy rate after IVF was 16% per patient. The latter treatment should be attempted in male immune infertility and in cases with a low sperm concentration, with or without abnormal sperm motility and/or morphology. In these circumstances, five pregnancies were attained out of 28 cycles in 14 cases. For similar sperm concentrations, the conception rate per cycle attained with techniques of assisted reproduction was more than twice that attained with conventional treatment of male infertility.

Female↗

PubMed1992

Increased pregnancy failure rates after clomiphene following assisted reproductive technology.

The obstetric outcome of 1941 in-vitro fertilization (IVF) and 1436 gamete intra-Fallopian transfer (GIFT) pregnancies reported from 25 units in Australia and New Zealand have been reviewed. Recently, gonadotrophin-releasing hormone analogues (GnRHa) have replaced clomiphene as part of many ovarian stimulation protocols. Clinical abortion rates after clomiphene (24.4% for IVF; 23.0% for GIFT) were not significantly higher than after GnRHa (20.7% for IVF; 17.9% for GIFT) when IVF and GIFT data were considered separately. However, the abortion rate for combined IVF and GIFT was significantly higher after clomiphene than after GnRHa. This pattern was found for most maternal age groups and causes of infertility although differences were not significant in all categories. The combined IVF and GIFT ectopic pregnancy rate of 6.7% for clomiphene was significantly higher than 4.1% for GnRHa. Because the mechanism of action of clomiphene for oocyte recruitment during folliculogenesis means that GnRHa cannot be used with clomiphene, luteinizing hormone (LH) levels are higher in clomiphene cycles than in GnRHa cycles. Clomiphene itself could cause the increase in pregnancy wastage or increased levels of LH during follicule genesis associated with the use of clomiphene may cause the observed pregnancy failures.

Abortion, Spontaneous↗

PubMed1997

The cellular activity of different sized follicles in cycles treated with gonadotrophin-releasing hormone analogue.

The activity of granulosa cells derived from different sized follicles surrounding oocytes of apparently comparable maturity was evaluated in hyperstimulated ovaries. Granulosa cells were obtained from women undergoing gamete intra-Fallopian transfer procedures who had been treated with gonadotrophin-releasing hormone analogue and gonadotrophins. Only follicles with oocytes of apparently comparable maturity were considered. Granulosa cells from large and small follicles (> or = 18 and < 15 mm diameter respectively) collected from each patient were cultured separately for up to 48 h in the presence or absence of follicle-stimulating hormone (FSH: 50 ng/ml) or insulin (at varying doses, 0.005-25 mg/ml). We found that aromatase activity was elicited by FSH plus insulin, but not by FSH alone, in granulosa cells from both large and small follicles. Progesterone production was maximal in granulosa cells from large follicles, and in these cells was insensitive to further stimuli, in contrast with those collected from small follicles. Prostaglandin oestradiol was secreted in large amounts by granulosa cells from large follicles. Cyclic adenosine monophosphate (cAMP) concentration did not differ between cells from large and small follicles. Our data demonstrate that there are significant differences in granulosa cells derived from different sized follicles with oocytes of apparently comparable maturity.

Adult↗

PubMed1989

Oocyte donation by gamete intra-fallopian transfer to amenorrhoeic and cycling patients given replacement steroids.

Thirteen procedures of oocyte donation by the gamete intra-Fallopian transfer (GIFT) technique are described. The patients included six women with premature ovarian failure, four normally cycling women with unexplained infertility who responded poorly to super-ovulation induction in preparation for GIFT, and lastly one woman carrier of a 16/21 balanced translocation. Two patients had oocytes donated on two occasions. Oocyte donors were recruited either among the patients' relatives (n = 4), or among GIFT or IVF patients (n = 8), who altruistically donated their extra oocytes. Donors were superovulated and oocytes collected laparoscopically or vaginally under ultrasound guidance. Donors did not suffer any complications. Recipients were given exogenous estrogens, and exogenous progesterone was added from the day of donation. Seven clinical pregnancies were obtained (53.8% per attempt); one set of triplets aborted at 14 weeks. Donation took place on replacement day 12-18 and pregnancies were obtained in patients receiving oocytes throughout this temporal window. The increasing availability of embryo-freezing facilities will probably reduce the number of ova available for donation. Therefore, the patients' families may become a precious source of donated eggs, especially for those patients having large families, with strong family ties.

Adult↗

PubMed2003

The effectiveness of IVF in unexplained infertility: a systematic Cochrane review. 2002,.

BACKGROUND: IVF is an accepted treatment for unexplained infertility. The objective of this review was to determine whether, for unexplained infertility, IVF improves the probability of live birth compared with: (i) expectant management; (ii) clomiphene citrate (CC); (iii) intrauterine insemination (IUI); (iv) IUI with controlled ovarian stimulation; and (v) gamete intra-Fallopian transfer (GIFT). METHODS: This was based on a Cochrane review. Randomized controlled trials (RCTs) which compared the effectiveness of IVF with expectant management, CC, IUI with or without controlled ovarian stimulation and GIFT were included. Patients included couples with unexplained infertility. Live birth rate per woman/couple was the main outcome measure. RESULTS: Nine RCT were identified. Five RCTs were included in the final meta-analysis. There were no comparative data for CC and live birth rates for expectant management or GIFT. There was no significant difference in clinical pregnancy rates between IVF and expectant management. There was no evidence of a difference in live birth rates between IVF and IUI either without (OR 1.96, 95% CI 0.88 to 4.36) or with (OR 1.15, 95% CI 0.55 to 2.42) ovarian stimulation. Clinical pregnancy rates with IVF were significantly higher compared with GIFT (OR 2.14, 95% CI 1.08 to 4.22) as were the multiple pregnancy rates (OR 6.25, 95% CI 1.70 to 23.00). Clinical heterogeneity was present among the studies. There was no evidence of statistical heterogeneity. CONCLUSIONS: The effectiveness of IVF in unexplained infertility remains unproven. Larger trials with adequate power are warranted.

Female↗

PubMed1994

High ovarian response in Yoruba African women during ovulation induction for assisted conception.

Fertile Yoruba women from western Nigeria have a much higher incidence of naturally conceived multizygotic twin and triplet pregnancies than Caucasians. The objective of the present study was to determine whether there are differences between infertile Yoruba and Caucasian women in terms of ovarian response in stimulate cycles for assisted conception. A total of 11 Yoruba women were scheduled for 14 in-vitro fertilization (IVF) and one gamete intra-Fallopian transfer (GIFT) cycles from 1990 to 1992. The Caucasian group consisted of 209 women scheduled for 213 IVF and 22 GIFT cycles during the same period. Buserelin, 500 micrograms subcutaneously daily, was started in the mid-luteal phase to achieve pituitary desensitization. Ovarian stimulation was with variable amounts of menopausal gonadotrophins. Human chorionic gonadotrophin (HCG) was given to trigger the ovulatory process. The Yoruba and Caucasian groups were similar in age and body weight, but significantly more Yorubas (45 versus 11%; P < 0.005) had ultrasound features of polycystic ovary syndrome (PCOS). The serum oestradiol concentration (3024 versus 2058 pg/ml; P < 0.05) and number of follicles > 14 mm in diameter (15.5 versus 9.5; P < 0.05) on the day of HCG were higher in the Yoruba group. The ovarian hyperstimulation syndrome (OHSS) was also more prevalent in the Yoruba group (20 versus 5%; P < 0.05). No difference was found in clinical pregnancy or embryo implantation rates. These results show a higher tendency toward exaggerated ovarian response in infertile Yoruba than Caucasian women, associated with a higher prevalence of PCOS. The risk of developing symptomatic OHSS is higher in Yoruba women.

Embryo Implantation↗

PubMed1997

Cumulative pregnancy and live birth rates after gamete intra-Fallopian transfer.

To evaluate the efficacy of gamete intra-Fallopian transfer (GIFT) the Kaplan-Meier life table method was used to analyse a patient cohort treated with GIFT between 1991 and 1994. In a tertiary referral centre for reproductive medicine, 1628 women with a median age of 33 years and various causes of infertility were included to calculate cumulative pregnancy and live birth rates. Age and cause of infertility were main factor variables and the study was based on a total of 2941 consecutive GIFT cycles, leading to a first clinical pregnancy, and 3052 cycles, leading to a first live birth. The cumulative pregnancy and live birth rates were 49.6 and 38.8% respectively, after three initiated cycles and 64.1 and 52.0% respectively, after five initiated cycles. The multiple pregnancy rate was 22.6%. The implantation rate of 13.1% after GIFT demonstrates that the developing embryo benefits from a period of exposure within the environment of the Fallopian tube. The present results indicate that approximately 50% of couples will have at least one live baby after five initiated GIFT cycles. Advancing age was a major negative prognostic factor for the cumulative live birth rate because of higher cancellation rates, lower implantation rates and higher pregnancy failure rates.

Adult↗

PubMed2004

Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study.

We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization-embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the delta-5 steroid synthesis pathway in the adrenals and/or in the ovary.

Adult↗

PubMed1999

Psychosocial stress and treatment outcome following assisted reproductive technology.

This study investigated the association between psychosocial stress and outcome of in-vitro fertilization and gamete intra-Fallopian transfer treatment. Ninety women, enrolled for treatment at a private infertility clinic, completed two self-administered psychometric tests (Bi-polar Profile of Mood States, POMS; and State-Trait Anxiety Inventory, STAI) and a questionnaire to ascertain demographic and lifestyle characteristics before the start of treatment. Approximately 12 months later an outcome measure was determined for each participant in terms of whether she was pregnant or not pregnant and the number of treatment cycles undertaken to achieve clinical pregnancy. The women's scores on the psychological tests were similar to published normative scores. On univariate analysis, history of a previous pregnancy was positively related to the probability of pregnancy and full-time employment, a more 'hostile' mood state and higher trait anxiety were associated with a lower cumulative pregnancy rate. A Cox multiple regression model found previous pregnancy history, trait anxiety, and the POMS agreeable-hostile and elated-depressed scales to be the most important lifestyle and stress variables predictive of pregnancy. The results emphasize the importance of psychosocial stress in treatment outcome but indicate that the relationships are complex. Further studies are required to validate whether these findings can be generalized to other populations.

Adult↗

PubMed1996

Heterotopic pregnancy after GIFT managed with expectancy: a case report.

A 29-year-old female patient visited our out-patient department (OPD) due to primary infertility in March 1993. Hysterosalpingography revealed cervical canal stricture. Gamete intra-Fallopian transfer (GIFT) was performed on Apr. 10, 1993 after ovulation induction. Three oocytes were placed into each Fallopian tube, then the patient was afflicted with lower abdominal discomfort and fullness 2 weeks later. Ovarian hyperstimulation syndrome (OHSS) was diagnosed. Ultrasonography showed intrauterine twin pregnancy and bilateral tubal pregnancy. During admission, supportive care for OHSS and expectant management only for ectopic pregnancies were given. OHSS resolved gradually. After a series of sonographic follow-up, disappearance of fetal heart beat (FHB) in the left ectopic gestational sac, resolution of bilateral ectopic gestational sacs and normal growth of intrauterine pregnancies were noted. On Dec. 16, 1993, the patient received cesarean section (C/S) due to twin pregnancy with vertex and breech presentation at the 37th gestational week. Twin A was female. Birth weight was 2590 gm. Apgar scores at 1 and 5 min. were 7 and 9. Twin B was also female. Birth weight was 2930 gm. Apgar scores at 1 and 5 main. were 8 and 9. Urinary bladder was injured accidentally at C/S. Repairment was done. The patient and her twins were discharged one week later in stable condition. Literature on heterotopic pregnancy after assisted reproductive technique (ART) was reviewed and discussed in this article.

Adult↗