Received IVF Treatment Research Articles

Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort.

BACKGROUNDLong-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown.METHODSWe identified a nationwide historic cohort of 19 146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile women not treated with IVF. In 1997–1999, data on reproductive risk factors were obtained from 65% of women and data on subfertility (treatment) were obtained from the medical records. The incidence of ovarian malignancies (including borderline ovarian tumours) through 2007 was assessed through linkage with disease registries. The risk of ovarian malignancies in the IVF group was compared with risks in the general population and the subfertile comparison group.RESULTSAfter a median follow-up of 14.7 years, the risk of borderline ovarian tumours was increased in the IVF group compared with the general population [standardized incidence ratio (SIR) = 1.76; 95% confidence interval (CI) = 1.16–2.56]. The overall SIR for invasive ovarian cancer was not significantly elevated, but increased with longer follow-up after first IVF (P = 0.02); the SIR was 3.54 (95% CI = 1.62–6.72) after 15 years. The risks of borderline ovarian tumours and of all ovarian malignancies combined in the IVF group were significantly increased compared with risks in the subfertile comparison group (hazard ratios = 4.23; 95% CI = 1.25–14.33 and 2.14; 95% CI = 1.07–4.25, respectively, adjusted for age, parity and subfertility cause).CONCLUSIONSOvarian stimulation for IVF may increase the risk of ovarian malignancies, especially borderline ovarian tumours. More large cohort studies are needed to confirm these findings and to examine the effect of IVF treatment characteristics.

MicroRNA array and microarray evaluation of endometrial receptivity in patients with high serum progesterone levels on the day of hCG administration

BackgroundTo determine the effect of higher progesterone (P) level on endometrial receptivity.MethodsThis was a prospective analysis conducted in the Reproductive Medical Center of Peking University Third Hospital. All patients received IVF treatment and canceled embryo transfer in the same cycle and were divided into group 1 (normal P; 7 patients) and group 2 (elevated P; 12 patients). Endometrial biopsies were performed 6 days after oocyte retrieval. The global miRNA and mRNA gene expressions in endometrial biopsies were investigated with a V4.0 miRNA probe and 22 K Human Genome Array. Fold ratios were derived to compare gene regulation between the groups. Spp1 and Ang gene expression was selected to verify the array results by RT-PCR and the protein expression of osteopontin and VEGF was determined using an immunohistochemical method.ResultsThere were 4 miRNA (all down-regulated) and 22 mRNA (13 up-regulated and 9 down-regulated) exhibiting differential expression between the groups on the microRNA and microarray chips. miRNA-451, Spp1, and Ang expression in RT-PCR verified the array results. Osteopontin and VEGF were also shown to have positive expression in the endometrium.ConclusionsData from microRNA and microarray analysis suggests dissimilar endometrial receptivity in patients with high P levels on the day of hCG, and elevated osteopontin and decreased VEGF had poor pregnancy rates.

Hormonal regulation of endometrial olfactomedin expression and its suppressive effect on spheroid attachment onto endometrial epithelial cells

Olfactomedin (Olfm) is a member of a diverse group of extracellular matrix proteins important for neuronal growth. Recent microarray studies identified Olfm as one of the down-regulated transcripts in receptive endometrium at the time of embryo attachment and implantation. However, the underlying molecular mechanisms that govern Olfm expression and its effect on embryo attachment and implantation remain unknown. The expression of Olfm in the human endometrium was investigated by real-time PCR, western blotting and immunohistochemistry on human endometrial biopsies from natural and ovarian stimulated cycles. To investigate the function of Olfm in trophoblast-endometrial cell attachment, an in vitro spheroid-endometrial cell co-culture study was performed. Human endometrial Olfactomedin-1 and -2(Olfm-1 and -2) transcripts decreased significantly from the proliferative to the secretory phases of the menstrual cycle. Olfm protein was strongly expressed in the luminal and glandular epithelium and moderately in the stromal cells of human endometria. Ovarian stimulation significantly decreased (P < 0.05) the expression of endometrial Olfm-1 and -2 transcripts in patients receiving IVF treatment when compared with those in the natural cycle. Importantly, recombinant Olfm-1 suppressed JAr spheroid attachment onto Ishikawa cells and this was not associated with changes of β-catenin and E-cadherin expression in trophoblast and endometrial cells. Decreased expression of Olfm during the receptive phase of the endometrium may allow successful trophoblast attachment for implantation.

Onset of late posttraumatic seizure after dehydroepiandrosterone treatment

To describe the first reported case of a seizure in a patient using the dietary supplement DHEA in an attempt to improve ovarian oocyte production. Case report. University-affiliated teaching hospital, neurologic department. A 30-year-old woman with fragile X syndrome and no history of any convulsive disorder who was receiving IVF treatment. Daily treatment with the dietary supplement DHEA. Generalized seizure. After 1 month of DHEA treatment, the patient was admitted with a generalized seizure. A generalized seizure, associated with concurrent intake of DHEA.

No Increased Incidence of Chromosomal Aberrations in Human Spermatozoa with Large Vacuoles by Injection into Mouse Oocytes

The effect of IMSI on avoiding fertilization with chromosomally abnormal sperm was examined in the present study. Normal shaped human sperm with large vacuoles were identified at 1,000× magnification on an inverted microscope with a 100×oil objective lens and were then cytogenetically analyzed after injection into mouse oocytes. In all semen samples from ten consenting patients receiving IVF treatment, more than 90% of the oval shaped sperm were determined to be abnormal, having vacuoles of various sizes on the head. Our cytogenetic analysis showed that the incidence of chromosome aberrations did not differ in sperm with large vacuoles from infertile patients and normal sperm from fertile donors. In addition, the risk of structural chromosome aberrations deriving from DNA lesions was very low in sperm with large vacuoles (9.1%) compared with elongated sperm (33.3%), the data for which was previously reported by us (2004). In conclusion, sperm DNA fragmentation dose not seem to explain the phenomenon reported by Berkovitz et al. (2006) in which injection of sperm with large vacuoles reduced pregnancy outcome. We also doubt whether IMSI is needed, since sperm with large vacuoles were easily identified at even 400 × magnification.

Shame in receiving IVF treatment affects the decision making process of the fate of cryopreserved embryos in Japanese infertility patients

Shame in receiving IVF treatment affects the decision making process of the fate of cryopreserved embryos in Japanese infertility patients

Intermittent vaginal injections of gonadotrophins for ovarian stimulation in IVF treatment

Intermittent vaginal administration of recombinant human FSH (rhFSH), for ovarian stimulation in IVF employing the concept of uterine first-pass effect and mesotherapy, was investigated. Injection of rhFSH (437 IU, counted as six ampoules) was carried out every 3 days into the vaginal mucosa of 66 participants receiving IVF treatment between November 2004 and August 2006. The primary outcomes were number of mature oocytes, number of good grade embryos, and term live birth rate (≥37 weeks gestation). On average, 2.94 days of injection and 16.35 ampoules of rhFSH were required to achieve proper follicular growth. Although fewer mature oocytes (5.27 ± 3.69) were retrieved, the number of good grade embryos (3.05 ± 1.95), number of embryos transferred (2.66 ± 1.70), pregnancy rate per cycle started [37.9%; 95% confidence interval (CI), 27.1–49.9], implantation rate (25.5%; 95% CI, 18.0–33.0), and term live birth rate (31.8%; 95% CI, 21.8–43.8) were comparable with conventional IVF treatments in this clinic.

Influence of pituitary suppression with triphasic or monophasic oral contraceptives on the outcome of in vitro fertilization and embryo transfer

To compare the clinical outcome of IVF treatment after pituitary suppression with two different oral contraceptives (OCs). 65 patients who received IVF treatment was classified into 2 groups based on the difference of OCs they used for pituitary suppression before ovarian hyperstimulation. Group 1 included 36 patients who received monophasic OCs. Group 2 included 29 patients who received triphastic OCs. Both groups received the OCs from the 5th day of the cycle for consecutive 21 days. The hormone profiles after OCs and clinical outcome of IVF treatment were compared between two groups. Two-sample t-tests and X2 tests were used for statistical analyses. P < 0.05 was considered statistically significant. The mean age and basal hormone profiles were comparable between two groups. After ovulation suppression with different OCs, the day 2 FSH and LH value revealed statistically significant difference between two groups(4.2+/-1.8 vs 6.0+/-2.6; 2.7+/-2.0 vs 4.2+/-3.3 respectively). The numbers of oocyte per retrieval and fertilization rate were comparable between two groups, but higher quality embryos as revealed by the cleavage speed were noted in the triphastic OCs group. Although statistically not significant, higher implantation rate and pregnancy rate were also noted in the triphastic OCs group. Different OCs for pituitary suppression can result in different hormone profiles. Ovulation induction in IVF treatment should be individualized according to these hormone changes to achieve the optimal clinical outcome. Triphastic OCs exceeds monophastic OCs in producing good quality embryo in IVF-ET treatment.

Endometrioma undergoing laparoscopic ovarian cystectomy: its influence on the outcome of in vitro fertilization and embryo transfer (IVF–ET)

To evaluate the effect of laparoscopic ovarian cystectomy for endometrioma on the clinical outcome of IVF treatment. Patients who received IVF treatment were retrospectively classified into two groups. Group 1 included 95 patients who received IVF due to tubal occlusion. Group 2 included 127 patients who had received laparoscopic ovarian cystectomy for endometrioma(s) followed by IVF treatment. Clinical outcomes of IVF treatment were compared between two groups. More oocytes were harvested per retrieval in Group 1 than Group 2 (p < 0.05). The fertilization rate was higher in Group 1 than Group 2 (p < 0.05). Although the implantation rate was higher in Group 2 (p < 0.05), the clinical pregnancy rate revealed no statistically significant difference between the two groups. Women who received ovarian cystectomy for endometriomas have fewer oocytes harvested during IVF treatment. However, their chance of pregnancy was comparable to patients with tubal problems who underwent IVF treatment.

Increased risk of early menopausal transition and natural menopause after poor response at first IVF treatment.

Our aim was to examine whether women who had a low number of retrieved oocytes at their first IVF attempt reach the menopausal transition and/or the natural menopause earlier than women of similar ages with a high number of retrieved oocytes. We conducted a retrospective cohort study among women in The Netherlands who received IVF treatment between 1983 and 1995. For the present study, we selected all cohort members who had a regular menstrual cycle at the time of the first visit to the gynaecologist (n = 4601). After a median follow-up of 5.5 years, 3871 (84%) women still had a regular menstrual cycle pattern, 547 (12%) women had entered the menopausal transition (i.e. no menses for 3-11 months, use of HRT or irregular menstrual cycles) and 27 (1%) women had reached natural menopause. We examined whether the quantity and the quality of the retrieved oocytes were related to an early menopausal transition and early menopause. The live birth rate per embryo transfer was used as indicative of the quality of the oocytes. The age-adjusted odds ratio (OR) for having entered the menopausal transition/natural menopause for women with a poor response (0-3 oocytes) at their first IVF attempt was 3.1 [95% confidence interval (CI) 2.4-3.8] compared with women with a normal response (>3 oocytes). Women who were stimulated with gonadotrophins during IVF treatment but did not undergo an IVF puncture because of an anticipated poor response (cancelled IVF cycle) had an age-adjusted OR of 3.2 (95% CI 2.3-4.3). There was no significant difference in the odds of reaching the menopausal transition/natural menopause, after adjustment for age and the number or retrieved oocytes, between women who did and did not have a live birth following their first embryo transfer (OR = 1.3; 95% CI 0.95-1.7). These results indicate that a low remaining quantity of oocytes, as reflected by a low number of retrieved oocytes at first IVF treatment, is an important predictor of the risk of an early menopausal transition/natural menopause. The quality of the oocytes did not affect the risk of an early menopausal transition/natural menopause once the number of retrieved oocytes had been taken into account. Our findings support the concept that the number of remaining follicles in the ovaries is one of the main aspects of reproductive ageing.

Embryo donation: attitudes toward donation procedures and factors predicting willingness to donate.

The aim of the study was to assess infertile couples' attitudes toward the procedures of embryo donation (ED) and to identify factors predicting interest in donation. Fifty-one couples who had received IVF treatment and had subsequently had embryos cryopreserved for >3 years were located and sent written information about the procedures for ED and possible implications of donation. A total of 49 couples agreed to participate in the study with 36 women and 31 men subsequently returning questionnaires describing their reasons for not claiming unused embryos and attitudes towards ED. Patients were supportive of donor screening procedures, but less comfortable sharing non-identifying information. Comfort levels declined as information became increasingly personal. Support for unconditional (i.e. the donation of embryos without conditions attached) and conditional (i.e. where couples could limit the donation of their embryos to persons/couples according to their preferences) models of donation was highly polarized and a substantial minority expressed strong opposition to each model. Willingness to donate was associated with greater comfort about disclosing personal information, a desire to know the outcome of donation and willingness to have future contact with a child, but not with current family size. Comfort in sharing information with a recipient couple is more important than acceptance of screening procedures, or attainment of family size goals in predicting willingness to donate embryos. Offering the option of conditional donation could increase the acceptability of ED for some patients.

Waiting for in vitro fertilization treatment: Spontaneous and ART live births

This study analysed the live birth rates in 760 couples referred in 1994 to St Mary's Hospital, Manchester, a non-fee-paying National Health Service (NHS) centre, who had waited for up to 4 years for IVF treatment. These live birth rates were compared with those of 199 couples referred at a similar time to Manchester Fertility Services, a fee-paying unit, where they received IVF treatment shortly after referral. The waiting time was advantageous in that 17.8% (135 of 760) of the couples referred to St Mary's Hospital conceived without IVF treatment, 60% within one year of referral. However, the waiting time was detrimental to women aged 30–34 in whom treatment was delayed by 3–4 years. Only 26.8% (204 of 760) of couples originally referred eventually received NHS-funded IVF treatment at St Mary's. A waiting time not exceeding 18 months would allow most spontaneous conceptions and reduce the adverse effect of prolonged waiting on the take-up rate for treatment and on the chance of success in the older women.

Mortality in a cohort of IVF patients.

Risks associated with IVF and related assisted reproduction technologies include complications of ovarian stimulation, surgical procedures and pregnancy itself. Serious complications are uncommon but may be potentially life threatening. The aims of this study were to compare the mortality rates of women who received IVF treatment, as well as those who were referred but were not treated, with the mortality rate in the general female population, to determine the maternal mortality rate following IVF conception and to establish whether any deaths had occurred as a result of treatment complications. Deaths were identified in a cohort of 29 700 Australian IVF patients by record-linkage with the National Death Index and a cancer registry. The all-cause mortality rates in IVF patients (treated and untreated) were significantly lower than in the general female population of the same age. In treated women, 72 deaths were observed and 125 deaths were expected giving an age-standardized mortality ratio of 0.58 (95% confidence interval 0.48-0.69). Two maternal deaths were identified in the 42 days of the puerperium. Complications of ovarian hyperstimulation syndrome could not be directly related to any of the deaths identified in this cohort. As well as providing some reassurance about the safety of IVF treatments, the findings point to the existence of a 'healthy patient effect' whereby the unhealthiest women in the population are deterred from pregnancy and infertility treatment.

Treatment of patients with long-standing unexplained subfertility with in vitro fertilization

Objective: To evaluate whether IVF is an effective treatment for long-standing unexplained subfertility. Design: Retrospective cohort study. Setting: Tertiary care infertility center in a university hospital. Patient(s): Two hundred two couples with unexplained subfertility of 2 years’ duration or more who attended the center for their first IVF attempt. Intervention(s): Couples were placed on a waiting list for IVF. They received no treatment until IVF was started. Main Outcome Measure(s): Pregnancy rate (PR) while on the waiting list and PR after IVF treatment. Result(s): Complete data sets were available for 131 couples. Seventeen of 131 women became pregnant while waiting for IVF treatment (PR 0.9% per exposure cycle), whereas 45 of 119 receiving IVF treatment became pregnant (PR 17% per IVF attempt). Conclusion(s): IVF treatment has substantial added value over waiting and is an efficient treatment for long-standing unexplained subfertility.

R-050. Is the presence of antiphospholipid antibodies meaningful in a group of patients randomly selected from those receiving IVF treatment?

R-050. Is the presence of antiphospholipid antibodies meaningful in a group of patients randomly selected from those receiving IVF treatment?

The relation between immunoglobulin G antibodies to Chlamydia trachomatis and poor ovarian response to gonadotropin stimulation before in vitro fertilization

Objective: To determine whether a relation exists between previous exposure to Chlamydia trachomatis and impaired ovarian response to gonadotropin stimulation. Design: Controlled clinical study. Setting: Two university IVF centers. Patient(s): Two hundred forty-two patients receiving IVF treatment and 81 control patients. Ninety-four patients with a poor response to IVF, defined by cycle cancellation in response to a daily stimulation dose of 300 IU of FSH, and 148 patients with a good response were matched for age. Twenty-eight pregnant controls and 53 controls of proven fertility also were included. Intervention(s): Serum samples were obtained from patients and controls. Serum levels of immunoglobulin (Ig) G antibodies to C. trachomatis were determined by ELISA. Main Outcome Measure(s): The prevalence of serum IgG antibodies to C. trachomatis in critically defined poor responders was compared with that of age-matched good responders. Result(s): A significantly higher proportion of poor responders had serum IgG antibodies to C. trachomatis compared with good responders (44.7% and 30.4%, respectively). Patients undergoing IVF had a significantly higher prevalence of IgG antibodies to C. trachomatis (36%) than did either pregnant or nonpregnant controls (12%). Conclusion(s): A significantly higher prevalence of serum IgG antibodies to C. trachomatis was observed in critically defined poor responders, suggesting a possible detrimental effect of C. trachomatis on subsequent ovarian function.

A randomized trial of in vitro fertilization versus conventional treatment for infertility

To evaluate the effectiveness of IVF in couples with infertility. Two hundred forty-five consecutive couples with infertility were randomized to receive one cycle of IVF treatment (experimental group) or to wait for a period of 6 months before receiving IVF treatment, during which time other infertility treatments could have been undertaken (control group). Patients were referred to the Fertility Clinic at Chedoke-McMaster Hospitals, a university-associated institution in Hamilton, Ontario, Canada, in which IVF has been offered to couples since 1984. Couples with infertility (mean duration of 65 months) not corrected by conventional treatment. They came from all socioeconomic classes, and the costs of IVF treatment, except medication, were covered by the Ontario Health Insurance Plan. Pregnancy was confirmed by ultrasound documentation of a gestational sac or histologic examination of tissue. Outcomes included livebirth, spontaneous abortion, and ectopic pregnancy. The overall pregnancy rate (PR) and the interval-to-pregnancy duration were compared in each group. Univariate analysis demonstrated a significant beneficial effect of IVF treatment in patients with bilateral severe tubal disease. Although in other diagnostic categories the crude and cumulative PRs in the experimental group were higher than in the control group, the differences did not reach statistical significance. Among the early IVF group, those with endometriosis had significantly more pregnancies when compared with other diagnostic categories. Although IVF increases the likelihood of pregnancy by 40% with severe tubal disease, the overall 31% increase associated with IVF was not statistically significant. There was a significant difference in favor of treatment in patients with severe bilateral tubal disease. For couples with other causes of infertility, the confidence limits around the treatment effect included unity. To reject the null hypothesis of no treatment effect, a larger sample size or a meta-analysis to combine the results of similar trials is required.