In Vitro Fertilization Attempts Research Articles

A low number of retrieved oocytes at in vitro fertilization treatment is predictive of early menopause

Objective: To investigate whether women with a low number of retrieved oocytes at the first in vitro fertilization (IVF) attempt have an increased risk of early menopause. Design: Nested case-control study. Setting: Twelve IVF clinics in the Netherlands. Patient(s): Women participating in a nationwide Dutch cohort study (OMEGA) of ovarian stimulation for IVF and subsequent gynecologic diseases (n = 26,428). Each patient who experienced natural menopause at or before 46 years (n = 38) was individually matched to five controls (n = 190) who had not yet entered menopause at the age the patient became postmenopausal. Intervention(s): None. Main Outcome Measure(s): Relative risk of reaching natural menopause at an early age (≤46 years), according to the number of retrieved oocytes at the first IVF attempt. Result(s): Women with a poor response (zero to three oocytes) had a relative risk of 11.6 (95% confidence interval: 3.9–34.7) of having an early menopause as compared with women who have a normal response (> three oocytes). Women who were stimulated with gonadotropins during IVF treatment but did not undergo an IVF puncture because of an anticipated poor response (canceled IVF cycle) had a relative risk of 8.3 (95% confidence interval: 2.9–23.9). Conclusion: These results suggest that women with a low number of retrieved oocytes at the first IVF treatment are more likely to become postmenopausal at an early age than women with a higher number of retrieved oocytes. Our study is the first longitudinal study to provide strong evidence for the quantitative aspect of the ovarian concept of reproductive aging.

Early pregnancy loss in in vitro fertilization (IVF) is a positive predictor of subsequent IVF success

Objective: To determine the significance of biochemical pregnancy losses and clinical spontaneous abortion (SAB) on outcomes of future IVF cycles. Design: Retrospective cohort study. Setting: Academic IVF program. Patient(s): Women with a history of unsuccessful IVF attempts undergoing IVF. Intervention(s): None. Main Outcome Measure(s): Clinical pregnancy rate. Result(s): Patients with an early pregnancy loss had a greater ongoing clinical pregnancy rate in the immediate next cycle when compared with those women who had a negative pregnancy test (37.3% vs. 27.3%). Patients with a history of a biochemical pregnancy or a clinical spontaneous abortion had an ongoing clinical pregnancy rate in the next cycle of 38.4% and 42.3%, respectively, compared with 27.3% in women who had a history of a negative pregnancy test. The cumulative pregnancy rate after the first IVF attempt was 54.1% in patients with a previous biochemical pregnancy loss, 61.4% in those with a previous clinical SAB, and 46.5% in women with a previous negative pregnancy test. Conclusion(s): Women who experience an early pregnancy loss after IVF have a greater likelihood of success in subsequent IVF cycles when compared with patients who fail to conceive.

Inherited thrombophilia and in vitro fertilization implantation failure

Inherited thrombophilia and in vitro fertilization implantation failure

Oocyte donation in infertility treatment

Oocyte donation in infertility treatment

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.

Comparison between intracytoplasmic sperm injection and in-vitro fertilization (IVF) with high insemination concentration after total fertilization failure in a previous IVF attempt

The aim of this prospective study was to evaluate whether couples with total fertilization failure in a previous in-vitro fertilization (IVF) attempt should be offered an additional IVF treatment with elevated insemination concentration or should be treated with intracytoplasmic sperm injection (ICSI). In 23 cycles 228 sibling metaphase II (MII) oocytes were randomly divided: 143 and 85 oocytes were utilized for ICSI and IVF respectively. Of the 143 injected (ICSI) oocytes, 90 (62.9%) were normally fertilized (two pronuclei), whereas 21 (14.7%) oocytes were damaged by the ICSI procedure. Of the fertilized oocytes 72 (80%) developed into transferable embryos. No fertilization at all was observed in the 85 sibling MII oocytes which were inseminated (P < 0.001). In all 23 cycles at least one embryo, obtained by ICSI, could be replaced. Eight pregnancies were achieved of which six resulted in the delivery of nine healthy children. In conclusion, for couples with no or almost no fertilization of oocytes in previous IVF attempts, ICSI appeared to be far superior to an additional IVF attempt with further elevated insemination concentrations.

Treatment of Male Infertility Due to Sperm Surface Antibodies: IUI or IVF?

This prospectively designed study was aimed at comparing the results of two different treatment protocols in 29 infertile couples with proven male immunological infertility, i.e. a positive (>50%) mixed antiglobulin reaction (MAR) test (IgG and/or IgA). In the first protocol (group I, n = 14) couples were treated with ovarian stimulation/ intrauterine insemination (IUI), followed by in-vitro fertilization (IVF) if no pregnancy occurred after three IUI cycles. In the second protocol (group II, n = 15), patients were treated with IVF as a first choice procedure. The decision to follow protocol 1 or 2 was made by the couples after information about financial costs and expected success rates (according to the literature) for both treatment options. In group I, nine patients (64.3%) conceived after a maximum of three IUI cycles whereas seven patients (46.6%) of group II became pregnant during the first IVF cycle. The take-home baby rate per started IUI or IVF cycle was 27.3% (9/33) and 44.4% (16/36) respectively with a take-home baby rate of 64.3% after three IUI cycles and 93.3% after three IVF attempts. To conclude, both IUI and IVF yielded unexpectedly high pregnancy rates in this selected group of patients with long-standing infertility due to sperm surface (predominantly IgG) antibodies. Since cost benefit analysis comparing superovulation IUI with IVF may favour a course of four IUI cycles, we advocate superovulation IUI as the first line therapy in male immunological infertility.

Predictive value of the results of a first in-vitro fertilization cycle on the outcome of subsequent cycles.

This study examines the relationship between the first cycle of in-vitro fertilization (IVF) and subsequent cycles. The results of all IVF cycles conducted at The Hammersmith Hospital or The Royal Masonic Hospital between 1988 and 1995 were studied including those cycles where egg recovery was abandoned due to poor ovarian response. All patients underwent a standardized treatment protocol. Of those women who achieved a clinical pregnancy during their first IVF attempt, 33% achieved a pregnancy during their second cycle, statistically significantly different from the 24% of patients conceiving during a second cycle who had failed to conceive during their first. 36% of those who achieved a biochemical pregnancy in their first cycle became pregnant in their second. Age was an important factor in the success of IVF treatment, with pregnancy rates of 48% in the 20-25 year age group falling to 8% in those aged > or =41 years. Cumulative pregnancy rates were 26% after one cycle, increasing to 43% after two cycles and reached 80% after seven cycles. A previous pregnancy significantly improved a couple's probability of conception in a later IVF cycle. Overall pregnancy rates per cycle were constant for the first three attempts. Cumulative pregnancy rates continued to rise to 72% after six cycles. Thus the more cycles a couple undergo (up to six) the greater their chance of a pregnancy.

Fertilization and early embryology: Zona opening of human embryos using a non-contact UV laser for assisted hatching in patients with poor prognosis of pregnancy

The aim of this study was to examine the safety and the efficiency of a 'non-contact' UV laser to assist hatching through zona opening of human embryos. Between January and November 1995 we performed zona drilling for assisted hatching using a new laser system (PALM UV Laser microbeam), operating in a 'non-contact' mode to create a hole in the zona pellucida of human embryos. In a randomized study, laser zona opening was applied on embryos from two groups of patients with repeated in-vitro fertilization (IVF) failures (two to four attempts): group A was composed of 107 patients who received mixed embryos (216 laser-treated and 223 not treated) and group B of 72 patients who received 218 laser-treated embryos only. Both groups were compared with a control group of 98 patients whose embryos were not laser treated (n = 407) (group C). The mean ages of all groups (38.1, 38.2 and 37.8 years respectively) and the number of IVF attempts (two to four attempts) were similar. The resulting clinical pregnancies were 39 (36.4%) in group A, 32 (44.4%) in group B and 19 (19.3%) in group C. The implantation rates/embryo were 9.3% in A, 16% in B and 5.1% in the control group. In total, 17 normal babies have been delivered (10 in group A and seven in group B). These results show that laser zona drilling increased the pregnancy and implantation rates in all the treated patients. The increase was slight but significant in patients of group A (P < 0.01 and P < 0.02), it was even higher in the patients of group B (P < 0.05).

The effect of human menopausal gonadotrophin and highly purified, urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down-regulated normogonadotrophic women

It has been suggested that the luteinizing hormone (LH) activity of human menopausal gonadotrophin (HMG) preparations used for ovarian stimulation in in-vitro fertilization (IVF) may have adverse effects on reproductive outcome. In the present prospective, randomized trial of 218 infertile couples this notion was investigated. A total of 114 women were treated with Pergonal (HMG group) and 104 with Fertinorm HP (HP-FSH group). The two groups were comparable with regard to duration of infertility, cause of infertility, age and number of previous IVF attempts and all had normal basal gonadotrophin concentrations before treatment was started. A standard hormonal treatment consisting of pituitary down-regulation with gonadotrophin-releasing hormone analogue (GnRHa) for 14 days starting on cycle day 21, followed by either HMG or highly purified follicle stimulating hormone (HP-FSH), three ampoules (225 IU) per day for 7 days, was used in all cases. The daily hormone dose was thereafter individualized according to the ovarian response. A maximum of two pre-embryos were transferred after 3 days of culture. Luteal support with progesterone (300 mg per day intravaginally) was used in all cases. Serum concentrations of oestradiol, FSH and LH were measured on days 1 and 8 of stimulation and on the day of oocyte retrieval. The mean number of days of stimulation, mean number of ampoules of HMG or HP-FSH used, mean total motile sperm count on the day of oocyte retrieval and mean numbers of oocytes retrieved (13.4 versus 13.7) or pre-embryos transferred (1.8 versus 1.8) were similar for both groups. Significantly (P < 0.05) more cycles in the HP-FSH group (17 = 16%) were cancelled due to complete failure of fertilization than in the HMG group (7 = 6%). The mean fertilization rate was significantly (P < 0.05) higher in the HMG group (56%) than in the HP-FSH group (50%), and significantly more transferable pre-embryos were obtained in the HMG than in the HP-FSH group (mean: 4.0 versus 3.2; P < 0.01). Serum hormone concentrations were similar to the two groups on stimulation day 1, but differed significantly with regard to FSH, LH and oestradiol on stimulation day 8. The clinical outcome was similar in the two groups, with an ongoing pregnancy rate (> 12 weeks of gestation) per started cycle of 33% in the HMG group and 29% in the HP-FSH group. The clinical abortion rates were similar (10 and 14%), and the implantation rate was 30% in each group. In conclusion, no detrimental effect of the LH activity of HMG on the clinical outcome of IVF in GnRHa down-regulated normogonadotrophic women was found. To the contrary, some beneficial effects of HMG on fertilization rates and pre-embryo development as compared with HP-FSH were demonstrated. These effects, as well as the differences in serum hormone concentrations during ovarian stimulation, may be caused by differences in LH content and/or in the composition of FSH isoforms of the HMG and HP-FSH preparations.

Are the characteristics of spermatozoa in the insemination medium useful for predicting in-vitro fertilization results?

To determine whether the characteristics of Percoll-selected spermatozoa are more predictive of in-vitro fertilization (IVF) results than are those of native semen, 118 semen samples from patients undergoing an IVF attempt were studied. Motility, using computer-assisted sperm analysis, and morphology were recorded before and after sperm selection on a Percoll gradient. Percoll selection increased the percentage of morphologically normal spermatozoa (58.2 +/- 19.9% versus 47.9 +/- 17.9%; p < 0.0001). This increase concerned almost all abnormalities and especially abnormalities of the midpiece (cytoplasmic droplets and bent tails). However, morphology of spermatozoa in the Percoll fraction had the same predictive value for IVF as did that for whole semen. Concerning motility, all parameters, except linearity, were improved by Percoll preparation, and their predictive value for IVF results was significantly higher in the Percoll fraction than in native semen. Therefore, it is concluded that, even if sperm characteristics are improved dramatically after Percoll selection, only motility analysis then gave more practical information than did analysis of sperm characteristics in native semen. This suggests that impairment of spermiogenesis, which presumably induces sperm abnormalities, is more important than are the actual characteristics of the spermatozoa.

Salpingectomy improves the pregnancy rate in in-vitro fertilization patients with hydrosalpinx

The objective of this study was to assess the impact on pregnancy outcome of excising hydrosalpinx(ges) in patients with repeated in-vitro fertilization (IVF) failures. A group of 15 patients who had previously undergone failed IVF attempts and had unilateral or bilateral hydrosalpinx was subjected to an operative laparoscopy with excision of the affected tube(s). Of these, 10 patients underwent a unilateral salpingectomy and five had a bilateral salpingectomy. Stimulated cycles of IVF and/or cryo-thaw cycles were then carried out post-salpingectomy and the results were compared to those of pre-salpingectomy cycles. There was no statistically significant difference between the number of mature eggs retrieved, peak oestradiol concentrations, number of days to human chorionic gonadotrophin administration, or number of pre-zygotes frozen in the stimulated cycles pre- versus post-salpingectomy. Pre-salpingectomy, 15 patients underwent 38 stimulated cycles and eight patients underwent 14 cycles with cryopreserved-thawed embryos, achieving one pregnancy from a fresh transfer that resulted in a miscarriage. Post-salpingectomy, eight patients underwent 12 stimulated cycles, achieving five clinical pregnancies (two miscarriages and three ongoing pregnancies, i.e. either delivered or a pregnancy > or = 20 weeks), and nine patients underwent 10 cycles with cryopreserved-thawed embryos, achieving four clinical pregnancies (one miscarriage and three ongoing). We conclude that excision of hydrosalpinx(ges) improves the pregnancy potential after IVF, and that new and repeat IVF patients should be counselled accordingly.

Autoimmune disorders: another possible cause for in-vitro fertilization and embryo transfer failure.

This study was undertaken to investigate the role of autoantibodies in association with in-vitro fertilization (IVF) and embryo transfer failure. Anticardiolipin, lupus anticoagulant, anti-deoxyribonucleic acid and antinuclear antibody, rheumatoid factor and antithyroid antibody concentrations were measured. The study group comprised 50 IVF patients with three or more previously failed cycles after embryo transfer. The control group comprised 80 computer-matched women: 40 who had conceived and delivered following three or less IVF and embryo transfer cycles, and 40 who were healthy nulligravidas. The incidence of autoantibodies in the study group was 22.0%, compared with 2.5% in the IVF control group (P < 0.05) and 7.5% in the nulligravida group (P < 0.05). In the study group, no statistical difference was found between the patients with unexplained infertility and those with mechanical infertility (23.0 and 20.8% respectively). The high occurrence of autoantibodies found in patients who failed at least three IVF and embryo transfer cycles could imply that these autoantibodies may be one of the possible causes of IVF failure in either mechanical or unexplained infertility. Further investigations are required to indicate the autoantibody profile as part of the work-up after three or more failed IVF and embryo transfer attempts.

Color-doppler velocimetry of uterine arteries in pregnant and nonpregnant patients during multiovulation induction for IVF

To evaluate uterine artery resistance during multiovulation induction in relation to the implantation rate in patients attending in vitro fertilization (IVF) cycles. Multiovulation induction for IVF was monitored by daily determination of the pulsatility index (PI) of the uterine arteries, obtained by a transvaginal probe (6.5 MHz) implemented with color-flow imaging. Doppler data were obtained from 5 days before hCG administration to the day of follicular aspiration. One IVF cycle was monitored in 70 patients. In 17 patients, 41 IVF cycles were monitored until a successful attempt occurred. In the 70 patients studied during one IVF attempt, the PI of the uterine arteries significantly varied (P < 0.001) in the different phases of the cycle. In the 24 patients who conceived, a significantly lower PI (P < 0.03) was found throughout the cycle. This result was mainly due to a highly significant difference of PI values observed the day after hCG administration (P < 0.005). In the 17 patients who conceived after 1 to 4 negative in vitro fertilizations, no significant difference in PI was observed in the uterine artery resistance in cycles in which implantation was or was not successful. Uterine artery resistance varies significantly during phases of the induction therapy. Uterine artery resistance is lower throughout the course of multiovulation induction in patients with higher pregnancy rates. The PI on the day after hCG administration was the best index of pregnancy rate. Low uterine artery resistance was present even in negative attempts in patients who eventually achieved a successful implantation. PI values < or = 3 can be considered a favorable prognostic factor for future IVF cycles.

Fertilization and early embryology: Morphometric parameters of living human in-vitro fertilization embryos; importance of the asynchronous division process

A total of 304 human pronuclear zygotes and cleaved embryos from the 2- to 9-cell stages, obtained during invitro fertilization attempts, were photographed and retrospectively analysed after transfer for their morphology and size in relation to their developmental stage, using the Imagenia programme of a Biocom 500 image analyser. Morphometric parameters were calculated from the perimeters, surface measurements, theoretical diameters and circularity factors for the different structures analysed. This report provides the morphometric characteristics of living embryos. For the whole population the mean values were: 157.4 microns for the external zona pellucida diameter, 121.8 microns for the internal zona pellucida diameter, 17.9 microns for the thickness of the zona pellucida and 117.2 microns for the embryo cell mass diameter. The morphometric characteristics of the pronuclear-stage population were significantly different from the cleaved cell stages. If the zona pellucida and cell mass embryo diameters increased slowly from the 2- to 9-cell stages, embryonic external diameters were higher and zona pellucida thicknesses were lower in odd than even number blastomere embryos. Preliminary results show that in cases where implantation occurs, the embryo has a lower zona pellucida thickness. A comparison of the different embryo cell stages confirmed the existence of an asynchronous division process during early embryo development. Global results show no evidence of morphometric differences between subpopulations of the embryos according to their microscopic grading. Deviations from the normal asynchronous division process, however, appear to be a new parameter to take into account during embryo scoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Pregnancy and birth after high serum progesterone concentrations during the follicular phase in an in-vitro fertilization cycle with gonadotrophin-releasing hormone agonist suppression

This case illustrates the possibility of achieving a pregnancy and birth when elevated progesterone concentrations (> 4 ng/ml) are present during the follicular phase (from 6 days before human chorionic gonadotrophin injection) of a gonadotrophin-releasing hormone agonist/menotrophin cycle for in-vitro fertilization (IVF). The present patient underwent three IVF/embryo transfer cycles in which progesterone concentrations were repeatedly increased from the midfollicular phase onwards. A pregnancy was achieved after the first IVF attempt but ended in a miscarriage in the 19th week of gestation. During the second IVF attempt an endometrial biopsy taken on the day of oocyte retrieval revealed an endometrial advancement of 2 days. A successful pregnancy and birth was again achieved after the third IVF attempt although progesterone concentrations were considerably increased from 6 days before the ovulatory stimulus.

Risk of thromboembolism in relation to an in-vitro fertilization programme: three case reports

Severe thrombotic events following ovarian stimulation for in-vitro fertilization (IVF) procedures in three women are reported. None of these patients presented any concomitant clinical sign of ovarian hyperstimulation syndrome. Coagulation inhibitors were in the normal range but cardiovascular risk factors were present. It is postulated that early thrombosis could be favoured by high endogenous plasma oestrogen concentrations subsequent to ovarian stimulation when associated with another risk factor. Our data are discussed in relation to previous publications. It is suggested that risk factors must be considered individually before each IVF attempt. In patients at high risk, clinical management of the post-transfer period is recommended.

Infertility: Five years' follow-up in two patients with borderline tumours of the ovary hyperstimulated by gonadotrophin therapy for in-vitro fertilization

In two women (36 and 30 years old) during infertility evaluation by ultrasound, an ovarian cyst was found on the left side (5 x 7 and 6 x 9 cm respectively). In both cases, it was decided to perform a unilateral salpingo-oophorectomy, keeping the other ovary (after a negative biopsy) for a future in-vitro fertilization (IVF) procedure with their own oocytes. The histology report for each patient showed the cyst was an epithelial borderline tumour. The first woman achieved a pregnancy and delivered a healthy baby after the first IVF attempt, while the second is currently undergoing her third attempt. This paper reports on a follow-up 5 years after the first IVF attempt.

Experience with subzonal insemination (SUZI) and intracytoplasmic sperm injection (ICSI) on unfertilized aged human oocytes

The aim of this study was to assess the fertilizability of unfertilized aged human oocytes from failed in vitro fertilization (IVF) cycles using SUZI and ICSI. A total of 363 oocytes which showed no fertilization after conventional IVF was subjected to assisted fertilization using SUZI or ICSI. The microinjected oocytes which were derived from 72 patients undergoing their first IVF treatment had an intact polar body and no signs of degeneration. SUZI was carried out in 265 oocytes and ICSI in the remaining 98. Significantly more oocytes were damaged after ICSI (9 vs 0.3%, P < 0.01). Normal fertilization rates were higher at 24 hr in both groups and occurred more frequently after ICSI, although the difference did not reach statistical significance. Abnormal fertilization occurred significantly more often after SUZI at 48 hr (P < 0.005), but not at 24 hr. Cleavage rates were significantly higher after ICSI (94.4 vs 57.1%, P < 0.025) at 24 hr, but this was not observed at 48 hr, although the ICSI group still showed better cleavage rates (33.3 vs 19.1%). There was no difference in embryo quality in either group. Our results indicate that micromanipulation rather than reinsemination should be carried out on unfertilized human oocytes from failed IVF attempts. Both techniques can be used to achieve fertilization which occurs more often after ICSI. However, the trauma from the former technique on the microinjected oocytes may impair the potential of the generated embryos to achieve pregnancy compared to SUZI. Prospective randomized trials are necessary to address the problem.

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.