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PubMed1990

IVF in the Nordic countries 1981-1987: a collaborative survey.

This report concerns the development of in-vitro fertilization (IVF) in the Nordic countries from the start of 1981 to January 1, 1988. All the 24 clinics in the Nordic countries which treat infertile couples with IVF participated in the study. The number of IVF clinics in the Nordic countries has increased from four in 1981 to 24 in 1987. In the same period, the number of people who spent some of their professional time as a part of an IVF team increased from 17 to 150. The majority of the clinics (19) based their activity mainly on governmental funding, while five of the clinics were private. During the period from 1981 to 1987, the Nordic clinic changed their methods of oocyte retrieval. In 1981, all oocyte retrievals were done using laparoscopy. Transvesical, ultrasound-guided follicular punctures domainated in 1985 and transvaginal ultrasound-guided punctures were used in 81.5% of the retrievals in 1987. A total of 852 pregnancies were reported. Of these, 313 (36.8%) were miscarriages, including 66 (7.7%) ectopic pregnancies. At January 1, 1988, 433 babies had been born, including 48 sets of twins, 14 sets of triplets and two sets of quadruplets. This gave a multiple birth rate of 18.2%. Premature births (less than 36 weeks of gestation) were reported in 14.6% of the births. Five babies (1.1%) died in the neonatal period and five (1.1%) were born with various types of malformation. One hundred and eight-eight pregnancies were in progress at January 1, 1988.

Adult↗
PubMed1991

A follow-up study of sperm preparation for IVF by swim-up in a solution of hyaluronate.

Spermatozoa prepared for in-vitro fertilization (IVF) by swim-up in a balanced salt solution containing hyaluronate gave rates of fertilization, cleavage and pregnancy which were not significantly different from those obtained with sperm prepared by swim-up in standard IVF medium followed by centrifugation. However, the content of prostaglandin F2alpha in the final sperm suspension was higher using hyaluronate but this seemed to be of no consequence for IVF. Thus, preparation of normal sperm samples for IVF may be simplified by performing swim-up in a balanced salt solution containing hyaluronate.

Cell Separation↗
PubMed1994

Immunity to zona pellucida in women with low response to ovarian stimulation, in unexplained infertility and after multiple IVF attempts.

A retrospective study was designed to assess the presence of antizona pellucida autoantibodies in in-vitro fertilization (IVF) patients in relation to low ovarian response, multiple IVF attempts and unexplained infertility. Antizona pellucida and antisperm antibodies were determined in serum samples obtained from 37 women undergoing IVF-embryo transfer and 20 fertile women. Antizona pellucida antibodies were measured using enzyme immunoabsorbent assay. Antisperm antibodies were evaluated by the immunobead binding method. Three of 10 patients with low response to ovarian stimulation had antizona pellucida antibodies in serum and one patient had antisperm antibodies. None of the other participants in the study and the control groups demonstrated measurable levels of serum antigamete antibodies. The results in this small group suggest an association between antizona pellucida antibodies and suboptimal response to gonadotrophins. It is indicated that repeated stimulation and puncture of ovaries in IVF procedures do not elicit autoimmunity to gametes.

Adult↗
PubMed2002

Risk factors for strong regret and subsequent IVF request after having tubal ligation.

OBJECTIVES: To identify and describe pre-sterilisation characteristics most consistently associated with intensive post-sterilisation regret and subsequent request for IVF. DESIGN: Case control study. SETTING: Fertility clinic in a tertiary referral urban hospital, Sydney, Australia. SAMPLE CASES: Ninety-seven sterilised women who underwent evaluation for IVF during the period 1986-1996; CONTROLS: 101 sterilised women who remained satisfied with their tubal ligation. MAIN OUTCOME MEASURES: Variables known at the time of sterilisation including age, number of living children, history of abortion, underlying medical diseases, marital status, race, education, and timing of sterilisation. RESULTS: In the multivariate analysis of data, age at the time of sterilisation had the most pronounced effect on strong regret. Women younger than 30 years old at the time of sterilisation were more likely to request IVF treatment than women 30 to 34 years old. A concurrent caesarean section was associated with a threefold risk (95% CI, 1.05-10.03) relative to an interval procedure. A strong protective effect (OR = 0.07; 95% CI, 0.01-0.65) was found for women with more than two children compared to childless women. The overwhelming reason stated by women requesting IVF was change in marital status, and the desire to have a child with the new partner. CONCLUSIONS: Women with such characteristics who are considering tubal ligation need further caution and counselling.

Adult↗
PubMed1996

The combination of two semen preparation techniques (glass wool filtration and swim-up) and their effect on the morphology of recovered spermatozoa and outcome of IVF-ET.

The aim of this prospective study was to relate sperm quality, especially sperm morphology, to the outcome of IVF results, when glass wool filtration (GWF) and swim-up were used in combination for the preparation of spermatozoa. A total of 60 ejaculates were analysed. GWF was compared with glass wool filtration/swim-up (GWF-SU) by using aliquots from the same semen samples to increase the precision of the comparison and to establish the cumulative effect of these two semen preparation methods on the morphology of the recovered spermatozoa. Sperm parameters were examined in native semen, in semen preparation samples after GWF and GWF-SU. The mean percentages for motility, morphology and velocity were improved significantly over those in fresh semen only when GWF-SU was used. GWF alone resulted only in a significantly higher recovery of motile spermatozoa. In semen preparation, 10% of spermatozoa with normal morphology appeared to be the cut-off point as there was a significantly higher recovery in fresh semen samples containing > 10% morphologically normal spermatozoa after GWF-SU. Outcome of IVF-ET following preparation with GWF-SU showed better results in comparison to the swim-up procedure alone, though this difference was not statistically significant. The cut-off point was also > 10% morphologically normal spermatozoa. Improvement in all aspects of IVF-ET occurred when native semen contained > 10% morphologically normal spermatozoa. It is concluded that GWF alone did not produce significantly better results but, in combination with swim-up, it resulted in significantly better sperm morphology and in an improved outcome of IVF-ET for fresh semen samples with > 10% morphologically normal spermatozoa.

Adult↗
PubMed2004

Seminal elastase-inhibitor complex, a marker of genital tract inflammation, and negative IVF outcome measures: role for a silent inflammation?

There is no consensus on whether and how male genital tract inflammation affects sperm fertilizing potential. The aims of this prospective study were to evaluate the elastase-inhibitor complex in seminal plasma (s-EI) level, a marker of male genital tract inflammation, in men undergoing in vitro fertilization (IVF) having no clinical signs of inflammation, and its association with semen characteristics, and the predictive role of s-EI for the outcome of IVF in terms of fertilization, embryo development to the blastocyst stage and pregnancy. The study involved 104 male partners of infertile couples with normal spermiogram undergoing IVF. On the day of oocyte retrieval, spermiogram and s-EI assessment using homogeneous immunoassay were performed. The outcome of IVF according to the s-EI level was assessed in 85 cycles with two or more oocytes. In 67 cycles embryos were cultured to the blastocyst stage. Spearman's and Pearson's correlation tests, chi-square test, and multiple linear and logistic regression analyses were used for statistical evaluation. Increased s-EI level (> or =250 microg/L) was detected in semen of 32% of men, and in 24% of men without leucocytospermia. We found an association between the s-EI level and semen leucocytes (r = 0.49, p = 0.004) but not with classical sperm characteristics. No correlation between the s-EI level and fertilization was observed. Increased s-EI levels were associated with a poorer blastocyst development rate (p = 0.03) and a higher number of arrested embryos (p = 0.04). Extended embryo culture to the blastocyst stage shows a negative effect of clinically silent male genital tract inflammation on embryo developmental potential.

Enzyme Inhibitors↗
PubMed1998

A rational basis for the use of combined heparin/aspirin and IVIG immunotherapy in the treatment of recurrent IVF failure associated with antiphospholipid antibodies.

PROBLEMS: 1) Does the administration of heparin and aspirin (H/A) in combination with intravenous immunoglobulin G (IVIG) improve in vitro fertilization (IVF) implantation and birth rates in patients with recurrent IVF failure? 2) Is the effect of such treatment related to the antiphospholipid antibody (APA) status of the patients concerned? METHOD OF STUDY: Subjects consisted of 89 women younger than 36 years of age whose infertility was a result of causes other than male infertility and who had experienced four or more failed IVF/embryo transfer procedures. Fifty-two women were APA+ (group A), and 37 were APA- (group B). All patients, regardless of their APA status, received H/A (5000 U sq bid), aspirin (81 mg po qd) from the inception of menotropin therapy along with IVIG (20 g) through a single infusion 3 to 10 days before egg retrieval. RESULTS: Twenty-two (42%) of group A and 7 (19%) of group B patients achieved live births (P = 0.020). CONCLUSIONS: IVF outcome is significantly improved when H/A and IVIG are administered to APA+ women with repeat IVF failures. APA- women do not seem to benefit from such treatment.

Adult↗
PubMed2005

Serum matrix metalloproteinase and tissue inhibitor of metalloproteinase concentrations in infertile women achieved pregnancy following IVF-ET.

PROBLEM: Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) play important roles throughout various stages of pregnancy, including embryo implantation, trophoblastic invasion, placentation in early gestation, and cervical dilatation in later gestation, and feto-maternal membrane lysis. It would be beneficial if assessment of serum concentrations of MMP and TIMP could predict successful implantation following in vitro fertilization-embryo transfer (IVF-ET). This study was performed to compare serum MMP and TIMP concentrations between patients with and without the establishment of pregnancy following ET. METHOD OF STUDY: Ten patients who conceived and 10 patients who did not after IVF-ET were entered in the present study. Only intra-uterine single pregnancies with uneventful courses to term were included in the study subjects. Blood samples were obtained at 7, 14 and 21 days after oocyte retrieval. Serum concentrations of MMP-1, MMP-2, MMP-3, and TIMP-1 were measured using enzyme-linked immunosorbent assay. These variables were compared with estradiol (E(2)), progesterone (P(4)), and betahCG levels in the patients' sera. Clinical pregnancies were diagnosed only when fetal heartbeat was visualized on ultrasound. RESULTS: There were no significant differences in serum MMP concentrations between the pregnant group and the non-pregnant group. However, serum TIMP-1 concentrations on Days 14 and 21 in the pregnant group were significantly higher than those in non-pregnant group [Day 14: 223.1 +/- 11.9 versus 177.5 +/- 20.6 ng/mL (P = 0.004); Day 21: 215.4 +/- 27.8 versus 181.5 +/- 27.4 ng/mL (P = 0.03)]. Serum TIMP-1 concentrations were also correlated with serum E(2) and P(4) levels (P < 0.0001), but not with those of the MMPs. None of MMP nor TIMP-1 were correlated with serum betahCG level. CONCLUSIONS: It was demonstrated that the patients who successfully conceived after IVF-ET showed significantly higher levels of TIMP-1 at 14 and 21 days after IVF-ET, but not at day 7; further work will be required to determine if serum TIMP-1 can be used to improve prediction of pregnancy outcome in these patients.

Adult↗
PubMed2006

IgG-antiphospholipid antibodies in follicular fluid of IVF-ET patients are related to low fertilization rate of their oocytes.

PROBLEM: Patients undergoing in vitro fertilization and embryo transfer (IVF-ET) failures show an increased incidence of antiphospholipid antibodies (aPL) in their blood. The physiological manifestations of aPL in this patient group are nonetheless controversial. Pathological effects of aPL on embryos in vitro have been documented. We questioned whether aPL if found in follicular fluids (FFs) could result in embryonic damage. METHOD OF STUDY: Blood from 44 patients with three or more IVF-ET failures were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of immunoglobulin (Ig)G, IgM and IgA aPL. Both the 29 aPL-positive and 15 aPL-negative patients gave permission for FF collection during their next IVF-ET attempt for additional aPL determinations. RESULTS: Patients with no aPL in their blood, had no aPL in their FFs. Patients with IgG and/or IgM aPL in their blood had IgG but not IgM in their respective FFs. CONCLUSIONS: The presence of IgG aPL in FFs and increased infertility length were significantly related to lower fertilization rates, independently. Follicular fluid IgG aPL appears as a risk factor in association with successful IVF-ET outcomes.

Adult↗
PubMed2003

The serum concentration of estradiol after embryo transfer and the decline from preovulatory levels may influence the success of IVF treatment.

AIM: To establish the influence that serum estradiol concentrations prior to oocyte retrieval and 3 days after embryo transfer have on the establishment of in vitro fertilization (IVF) pregnancy. METHOD: Preovulatory (day-0) and luteal-phase (day-6) estradiol concentrations were retrospectively analyzed in 310 infertile patients, undertaking 1st-cycle conventional IVF or intracytoplasmic sperm injection. RESULTS: The IVF treatment success is significantly reduced in patients with an estradiol level <600 pg/ml and also when a rapid decline in luteal-phase estradiol concentrations from preovulatory concentrations (day 0:day 6 ratio) was exhibited. CONCLUSION: A day 0:day 6 estradiol ratio >5 and a serum estradiol concentration <600 pg/ml may adversely impact on the establishment of pregnancy in IVF.

Adult↗
PubMed2006

Role of latent genital tuberculosis in repeated IVF failure in the Indian clinical setting.

Genital tuberculosis is reported to be a major pelvic factor causing infertility in Indian women and often exists without any apparent signs and symptoms. The role of latent tuberculosis in repeated IVF failure in unexplained infertility is examined. 81 women with unexplained infertility having repeated IVF failure tested for Mycobacterium tuberculosis using PCR, ZN staining and BACTEC-460 culture were selected. Fresh IVF-ET or frozen embryo transfer (FET) was attempted on patients successfully treated with anti-tubercular drugs (ATD). ATD-treated fresh cycles (group A1) and frozen cycles (group B1) were compared to previously failed fresh cycles (group A2) and FET attempts (group B2), respectively. Main outcome measures were gonadotropin required, terminal E2, number of oocytes retrieved, fertilization rate, embryo quality, endometrial thickness and sub-endometrial blood flow (V(max)). Gonadotropin required in group A1 was significantly less as compared to group A2. Number of oocytes retrieved and grade I embryos, endometrial thickness and V(max) were significantly higher in group A1. Endometrial thickness and V(max) were significantly increased in group B1 as compared to B2. The study indicates that latent tuberculosis should be considered in young Indian patients presenting with unexplained infertility with apparently normal pelvic and non-endometrial tubal factors and repeated IVF failure.

Adult↗
PubMed1997

The neonatal consequences and neonatal cost of reducing the number of embryos transferred following IVF.

This clinical audit project examined the effects of change of policy between 1990 and 1993 transferring an average two (maximum three for particular cases) embryos to women undergoing IVF in the West of Scotland programme. All women who achieved clinical pregnancy in 1990 (92 women) and 1993 (93 women) as a result of the IVF programme were included in the study. The hospital records of women via the programme were analysed. The results of the study showed that there was a significant reduction in the rate of multiple pregnancy, preterm birth and low birth weight babies in the 1993 group (new policy). The cost of neonatal intensive care in 1993 for babies born following IVF was about nine times lower than that in 1990 (old policy). This study concluded that a policy of transferring two embryos (or three for particular cases) to women in an IVF programme, had improved the perinatal outcome and reduced the cost of the neonatal service for those babies.

Chi-Square Distribution↗
PubMed1988

Hysteroscopy in an IVF-ER program. Clinical experience with 360 infertile patients.

Three hundred and sixty patients underwent hysteroscopy before entering the IVF program. The procedure was successful in 332 patients; obstructive tubal disease was present in 247 (70%); 148 showed uterine abnormalities (44.5%) such as endometrial polyps, adhesions, hypoplasia, malformations, or severe cervical stenosis; 114 patients had normal hysterographic findings, in whom hysteroscopy revealed a false-negative rate of 36.8%. In 281 patients (84.6%) hysteroscopy was carried out under general anesthesia, in most cases associated with laparoscopy. There were no anesthetic complications, uterine perforations or other significant problems. In an IVF program, hysteroscopic evaluation can reduce the failure rate due to intra-uterine abnormalities. Hysteroscopy, which permits one to optimize an IVF attempt, becomes an essential procedure before introducing a patient into an IVF program.

Adult↗
PubMed1996

Does hyperandrogenism explain lower in vitro fertilization (IVF) success rates in smokers?

BACKGROUND: Our aims were to elucidate whether a decreased fertility in smoking women treated by in vitro fertilization (IVF) could be related to a divergent hormonal response to the controlled stimulation prior to IVF, to study the effect of smoking on the ovarian endocrine milieu and to possibly identify factors that might be detrimental to oocyte fertilization. METHODS: Serum and follicular fluid concentrations of estradiol-17 beta (E2), progesterone (P), testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), DHA sulfate (DHAS), sex hormone-binding globulin (SHBG) and serum cortisol were studied in 50 non-smoking and 50 smoking women in an IVF program. Follicular fluid concentrations were also compared in follicles which gave rise to cleaved oocytes (TYPE I) and follicles which failed to yield fertilized oocytes (TYPE II) in the same woman. RESULTS: The fertilization rate did not differ significantly between the two groups, but the live birth rate was 30% in non-smokers and 4% in smokers. During treatment, serum A-4, DHAS and the T/SHBG-ratio were significantly higher in smokers than in non-smokers. In the TYPE I follicles, smokers had higher follicular fluid concentrations of A-4 and DHA and a higher E2/P ratio. The TYPE II follicles in smokers had higher A-4 and T and lower E2 levels. CONCLUSIONS: Smoking women have a relative hyperandrogenism of ovarian origin, which may contribute to the lower pregnancy rate at IVF in this group.

Adult↗
PubMed1992

Embryo associated immunosuppressor factor(s) secreted by preembryo and serum estradiol levels are predictive of pregnancy outcome: effect of gonadotropin releasing hormone agonist (GnRHa) treatment of patients undergoing in vitro fertilization and embryo transfer (IVF-ET).

The aim of the present study was to determine whether (i) the secretion of embryo associated immunosuppressor factor (EASF) by preimplantation embryo and serum estradiol (E2) play a cooperative role in pregnancy outcome and (ii) whether this association was affected by gonadotropin releasing hormone agonist (GnRHa) pretreatment of IVF-patients for ovarian stimulation. EASF activity was measured using concanavalin A-induced lymphocyte proliferation assay in 251 IVF-culture media obtained from 59 patients undergoing IVF-ET. EASF activity in embryo growth media, cycle day 3 serum E2 level and peak E2 levels were correlated with pregnancy outcome. Results indicate that in GnRHa non-treated patients (i) the immunosuppressive activity of embryo growth media significantly (p less than 0.05) differed between the patients with varying concentration of day 3 serum E2, (ii) the presence of immunosuppressive activity in the embryo growth media was associated with success of pregnancy in patients with day 3 serum E2 level of 21-40 pg/ml (p less than 0.005) and in patients with peak E2 level in serum of less than = 1500 pg/ml (p less than 0.05). No association in immunosuppressive activity, serum E2 level and successful pregnancy was seen in GnRHa treated patients. This preliminary study suggests that the concentration of serum hormones and factors that are altered due to GnRHa pretreatment of IVF-patients may affect the cooperative role played by EASF, E2 and other factors in the success of pregnancy.

Blastocyst↗
PubMed1995

Hormonal profiles in successful and unsuccessful implantation in IVF-ET after combined GnRH agonist/gonadotropin treatment for superovulation and hCG luteal support.

The luteal phase of in vitro fertilization-embryo transfer (IVF-ET) cycles has come under great scrutiny as the cause for the discrepancy between fertilization rates (> 70%) and pregnancy rates (around 20%) in most IVF programs is sought. The effects of the various stimulation protocols on the subsequent hormonal events of the luteal phase are both important and controversial but information regarding cycles where ovarian stimulation has been carried out with gonadotropins under pituitary suppression is scanty. The effect of high levels of estrogen in the late follicular phase and around the time of implantation is a matter of concern. As combined gonadotropin-releasing hormone analog (GnRH-a) gonadotropin treatment for superovulation is associated with supraphysiological ovarian steroid levels, both in the follicular and luteal phase of IVF cycles, we compared preovulatory (estradiol), midluteal (estradiol, progesterone and prolactin) and late luteal (estradiol and progesterone) hormone levels in on-going pregnancies, abortions and non-conception cycles in 222 patients accomplishing their first IVF-ET attempt who received such ovarian stimulation therapy. For both successful and unsuccessful implantation cycles, estradiol on the day of human chorionic gonadotropin (hCG) administration correlated positively with progesterone and estradiol levels and negatively with the progesterone/estradiol ratio in the midluteal phase. Mean peak follicular estradiol, midluteal estradiol and progesterone levels, mean mid- and late luteal progesterone/estradiol ratio, and mean midluteal prolactin concentration, were similar in the three groups studied. The mean late luteal estradiol and progesterone in the on-going pregnancy group were significantly higher than in non-conception cycles (p < 0.005 and p < 0.001, respectively) as a reflection of trophoblastic hCG production. Forty-eight patients (21.6%) had hyperprolactinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Do changes in growth hormone levels correlate with IGF-I levels in patients undergoing IVF-ET?

It has been suggested that adjunctive growth hormone (GH) therapy improves ovarian response and in vitro fertilization (IVF) outcome in specific groups of patients. The correlation between insulin-like growth factor (IGF) and GH is well established. The aim of this study was to determine whether changes in plasma GH correlate with IGF blood levels in patients during IVF treatment. Thirty-six women undergoing IVF and embryo transfer (ET) were examined. Ovarian stimulation was carried out by gonadotropin-releasing hormone agonists (GnRHa) and gonadotropins. Blood was drawn at the early and late follicular phase, on the day of human chorionic gonadotropin (hCG) injection and at the mid- and the late luteal phases. The samples were assayed for IGF-I, IGF-II, IGF-binding protein-3 (IGF BP-3), GH and estradiol. According to the IGF-I and GH plasma levels, patients were divided into three major groups: Group I consisted of patients in whom peak levels of GH reached more than 4 ng/ml and IGF-I decreased significantly. In this group, estradiol levels were 1863 +/- 149 pg/ml. Group II consisted of patients in whom peak blood GH levels did not exceed 2.5 ng/ml and the IGF-I level remained unchanged. In this group estradiol levels were 630 +/- 57 pg/ml. Group III consisted of patients in whom blood GH levels were low and remained unchanged while estradiol levels were 1600 +/- 420 pg/ml. In this group no significant increase in IGF-levels were observed. There was no significant change in the levels of either IGF-II or IGF BP-3 in any of the groups. We can conclude that (1) there is a negative correlation between GH and IGF-I plasma levels in patients undergoing controlled ovarian hyperstimulation (COH)-IVF, when levels of estradiol and GH are elevated; (2) plasma levels of IGF-I under ovarian hyperstimulation are probably regulated by a multifactorial system; and (3) no correlation was found between the plasma levels of IGF-I and those of IGF-II and IGF BP-3 in all patient groups.

Adult↗
PubMed1999

[The comparison of efficiency of supplement of the second phase in the program IVF-ET by dydrogesterone and progesterone].

The retrospective study was carried out to compare effectiveness of progesteron and dydrogesteron luetal phase support following in vitro fertilisation and embryo transfer. Two hundred and fifty eight patients undergoing IVF ET received progesteron in itramuscular injections. Two hundred sixty patients received dydrogesteron three times daily p.o. There were no differences in stimulation protocols, indications for IVF and IVF procedures. Pregnancy rate, implantation rate and spontaneous abortion rate were similar in both groups. The effectiveness of luteal phase support in patients undergoing IVF ET program by dydrogesteron and progesteron is similar with significantly lower costs for the last one.

Adult↗