Assisted Reproduction Treatment Outcome Research Articles

Upregulation of steroidogenic enzymes and ovarian 17beta-estradiol in human granulosa-lutein cells by Cordyceps sinensis mycelium.

There is increasing evidence that 17beta-estradiol (E2) directly influences the quality of maturing oocytes and thus the outcome of assisted reproduction treatment. Although Cordyceps sinensis (CS) mycelium, a Chinese herbal medicine, is believed to enhance libido and fertility in both sexes, the mechanism of its effect in women has not been determined. The aim of the present study was to evaluate the effects of CS on steroidogenic enzyme expression and E2 biosynthesis in human granulosa-lutein cells (GLC). We found that CS induced E2 production by GLC in a dose- and time-dependent manner and that a 3-h treatment with CS induced increased levels of mRNAs coding for the P450 side chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and aromatase. Western blot analysis demonstrated that, after treatment with CS for 3 h, protein levels of steroidogenic acute regulatory protein (StAR) and aromatase were upregulated while P450scc and 3beta-HSD levels showed no substantial change. New protein synthesis was required for CS-induced E2 production because it was abrogated by cycloheximide pretreatment. Addition of 22(R)-hydroxycholesterol, thus bypassing the need for StAR protein, did not induce as much E2 production as CS treatment, indicating that upregulation of StAR protein was not the only factor contributing to CS-induced steroidogenesis. Cotreatment of GLCs with CS and aminoglutethimide, an aromatase inhibitor, completely abolished CS-induced E2 production. In conclusion, treatment of GLCs with CS results in increased E2 production due, at least in part, to increased StAR and aromatase expression. These data may help in the development of treatment regimens to improve the success rate of in vitro fertilization.

Concentrations of gonadotrophins and steroids in pre-ovulatory follicular fluid and serum in relation to stimulation protocol and outcome of assisted reproduction treatment

In this prospective, randomized study, concentrations of gonadotrophins and steroids in pre-ovulatory follicular fluid (FF) and serum were related to type of stimulation protocol as well as to the outcome of assisted reproduction in 280 women subjected to the long protocol gonadotrophin-releasing hormone (GnRH) agonist pituitary down-regulation and ovarian stimulation with either human menopausal gonadotrophin (HMG) or recombinant FSH. In the women treated with HMG, concentrations of LH, FSH, oestradiol and androstenedione in FF were significantly higher, and those of human chorionic gonadotrophin (HCG) and progesterone significantly lower, than in the women treated with recombinant FSH (rFSH). More women became pregnant and delivered in the HMG than in the rFSH group. These differences, however, were not statistically significant. Concentrations of FSH in serum and of FSH and LH in FF were significantly higher in conception than in non-conception cycles, whereas all other hormone concentrations in FF and serum were similar. The present study demonstrates that the pre-ovulatory follicular fluid hormone profile is significantly influenced by the gonadotrophin preparation used for ovarian stimulation, and suggests that ovarian stimulation with HMG results in an intra-follicular hormone profile more similar to that characterizing conception cycles than stimulation with rFSH. However, as the present data represent means of FF hormone profiles, they do not allow the conclusion of a direct correlation between the intra-follicular concentration of a certain hormone and the ability of the corresponding embryo to implant and establish an ongoing pregnancy.

LH serum levels during ovarian stimulation as predictors of ovarian response and assisted reproduction outcome in down-regulated women stimulated with recombinant FSH.

There has been much debate about the effect of 'residual' LH levels in normogonadotrophic women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH ovarian stimulation. The aim of this prospective study, where receiver-operating characteristic (ROC) analysis was used, was to assess further the usefulness of serum LH levels as predictors of ovarian response, assisted reproduction treatment outcome, and the outcome of pregnancy when measured throughout the ovarian stimulation period in a large cohort of such assisted reproduction treatment women. A total of 246 consecutive women undergoing their first cycle of IVF or ICSI treatment were included in this study. Blood samples for hormone analyses were obtained on day S0 (the day when pituitary suppression was evidenced) and every other day from stimulation day 5 (S5) until the day of hCG injection. LH serum levels throughout ovarian stimulation treatment were similar for cancelled (n =32) versus non-cancelled (n = 214) cycles, non-conception (n = 132) versus conception (n = 82) cycles, and ongoing pregnancy (n = 66) versus early pregnancy loss (n = 16) groups. There was no correlation between LH serum levels in non-cancelled cycles and parameters of ovarian response and assisted reproduction treatment outcome. ROC analysis showed that serum LH concentration during ovarian stimulation was unable to discriminate between cancelled and non-cancelled cycles, conception versus non-conception cycles, or early pregnancy loss versus ongoing pregnancy groups. Serum LH measurements during ovarian stimulation with recombinant FSH under pituitary suppression in normogonadotrophic women undergoing assisted reproduction treatment cannot predict ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy. Thus, there is little underlying physiological support for the addition of LH in stimulation protocols if daily doses of an appropriate GnRH agonist (leuprolide or triptorelin having lower potency than buserelin) and a step-down regimen of recombinant FSH administration are used.

Does egg-sharing compromise the chance of donors or recipients achieving a live birth?

To evaluate the effect of egg-sharing and the outcome of assisted reproductive treatment (ART) in standard IVF/ICSI patients, egg-sharing donors and egg-sharing recipients. Descriptive cohort study to evaluate 276 egg-sharing cycles involving 192 egg-sharers, 274 recipient cycles receiving eggs from egg-sharers and 1098 non-egg-sharing standard IVF/ICSI cycles from January 1998 to December 2002. Patients were divided into three groups: group A, egg-sharers; group B, non-egg-sharers, age <36 years, FSH <10 IU/l, BMI <30 kg/m(2); and group C, egg-sharing recipients, all ages. Duration and amount of gonadotrophin required to achieve follicular maturity, number of eggs collected and donated, fertilization rate, pregnancy rates and live birth rates were compared between donor, recipient and standard IVF/ICSI patients. The chi(2 )test was used to test for statistical significance (P < 0.05). There was no significant difference in pregnancy rate and live birth rate of egg-sharers, group A (42.0%, 33.0%), non-egg-sharers, group B (40.0%, 30.9%) and recipients, group C (41.4%, 28.6%). The number of oocytes collected, number of mature follicles and amount of gonadotrophin used was not significantly different between the two groups (A and B). The average number of embryos transferred and the mean number of eggs allocated between egg-sharers and recipients was not statistically different. Egg-sharing does not compromise the chance of achieving a pregnancy or live birth for the egg-sharer or the recipient as compared to standard IVF/ICSI patients. The egg-sharers were not at a higher potential risk of ovarian stimulation syndrome and there was no imbalance of egg allocation.

Conception rates following assisted reproduction in poor responder patients: a retrospective study in 300 consecutive cycles

Poor response to ovarian stimulation for assisted reproduction treatment is a therapeutic challenge. Oocyte donation may be unacceptable to some patients, and many couples opt to continue with treatment despite low follicle numbers. Minimal data are available regarding conception rates in poor responders who elect to undergo oocyte retrieval. This study summarizes the outcome of assisted reproduction treatment in poor responders who produced four or fewer oocytes during ovarian stimulation, in order to provide better counselling to such patients in the future. Embryo transfers were performed in 208 of 300 cycles demonstrating poor ovarian response. Pregnancy rate (PR) (15.9%) was significantly higher in patients in whom four oocytes were retrieved, compared with patients in whom one or two oocytes were retrieved (2.3 and 4.3% respectively). Younger patients (≤34 years) had significantly higher PR (19.5%) compared with older patients (≥35 and ≤39 years, PR 7.2% and ≥40 years, PR 1.5% respectively). One hundred and twenty-six age-matched normal responders in whom three embryos were transferred had higher implantation rates (15.3%) and PR (37.3%) compared with poor responders in whom three embryos were transferred (6.6 and 16.6% respectively; P < 0.05). In this regard, patient age, number of oocytes retrieved and number of embryos available for transfer determine prognosis for the success of IVF in patients who respond to ovarian stimulation with four or fewer follicles for assisted reproduction treatment.

Cycle-to-cycle variation in utero-ovarian hemodynamic indices in ovarian stimulation and natural cycles of the same women and its effect on the outcome of assisted reproduction treatment

Objective: To investigate the blood flow parameters between cycles of the same women to assess whether parameters predicting a successful pregnancy in a stimulation cycle could be used to determine the outcome of subsequent natural cycles. Design: A prospective study. Setting: Assisted reproduction unit, the University of Hong Kong. Patient(s): Fifty-eight IVF cycles and 40 natural cycles were evaluated. Intervention(s): Assessments of the utero-ovarian pulsatility indices (PIs), resistance indices (RIs), and endometrial color signals. Result(s): In IVF cycles, the pregnancy rate (27%) was similar to that in frozen-thawed embryo transfer (FET) (28%) cycles. The utero-ovarian PIs and RIs in IVF cycles were significantly lower than those in the natural cycles. There was a significant correlation between the uterine PI in stimulation cycles and that in natural cycles. In IVF cycles, the pregnancy rate declined significantly when the uterine PI was >2.70 and the RI was >0.9. In FET cycles, no decline in pregnancy rate was seen. Conceptional FET cycles showed significantly higher uterine PI, uterine RI, and endometrial color signals compared with conceptional IVF cycles. Conclusion(s): Hemodynamic parameters in stimulation cycles are different from those in natural cycles, and the values of various parameters in predicting pregnancy are also different.

Effects of previous ovarian surgery for endometriosis on the outcome of assisted reproduction treatment

Endometriosis affects 2–50% of women at reproductive age. Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility. Also, the removal of ovarian endometrioma might lead to a reduction in the follicular reserve and response to stimulation. Therefore, the aim of this study was to evaluate the effect of previous ovarian surgery for endometriosis on the ovarian response in assisted reproduction treatment cycles and its pregnancy outcome. A total of 61 women, with primary infertility and previously having undergone ovarian surgery for endometriosis, who had received 74 IVF/intracytoplasmic sperm injection (ICSI) cycles, were studied (study group). A further 74 patients with primary infertility who underwent 77 IVF/ICSI cycles within the same period of time, at the same clinic and without previous ovarian surgery or endometriosis were studied as a control group. Patients were matched for age and treatment performed. Patients ≤35 years with previous ovarian surgery had fewer retrieved oocytes than the patients in the control group ( P = 0.049). The number of ampoules used for ovulation induction, duration of folliculogenesis (days), number of follicles and fertilization rate was similar in both groups. The same was observed for pregnancy rates, with 24 patients (53.3%) having had previous ovarian surgery and 27 (56.2%) in the control group becoming pregnant. Patients >35 years with previous ovarian surgery needed more ampoules for ovulation induction ( P = 0.017) and had fewer follicles and oocytes than women in the control group ( P = 0.001). Duration of folliculogenesis was similar in both groups, as was fertilization rate. A total of 10 patients achieved pregnancy in the study group (34.5%) and 14 (48.3%) in the control group. Although a lower pregnancy rate was observed in patients who had undergone previous ovarian surgery, this difference was not statistically significant ( P = 0.424). In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. Therefore, for infertile patients, non-surgical treatment might be a better option to avoid reduction of the ovarian response.

Uterine leiomyomas and their effect on in vitro fertilization outcome: a retrospective study.

The effect of uterine leiomyomas on the outcome of in vitro fertilization (IVF) treatment has been controversial. This study was undertaken to clarify influence of fibroids on IVF success, in a large population with age and other potential confounding variables controlled for in the analysis. A population of 141 patients with and 406 without leiomyomata undergoing their first IVF cycle was studied. The association between uterine leiomyomas and assisted reproduction treatment outcome was not statistically significant (OR = 0.73, 95% CI: 0.49-1.19, p = 0.21) after controlling for age and other risk factors. Also, fibroids neither affected the risk of spontaneous abortion (OR = 1.06, 95% CI: 0.44-2.60) nor the risk of ectopic pregnancy (OR = 0.78, 95% CI: 0.08-8.02). Location of fibroids (intramural vs. submucosal/subserosal) and their size had no significant effect on pregnancy outcome. Results from our analyses indicated that in vitro fertilization outcome was not affected by the presence of uterine leiomyomas. Therefore, in patients with normal uterine cavities and fibroids less than a certain size (i.e., < 7 cm), undergoing myomectomies as a prerequisite for assisted reproduction treatment is seriously questionable.

Day 3 serum inhibin B and FSH and age as predictors of assisted reproduction treatment outcome.

Recent reports investigating the value of basal inhibin B determination as a predictor of ovarian reserve and assisted reproduction treatment have led to discordant results. This study was undertaken to further assess the relative power of day 3 inhibin B and follicle stimulating hormone (FSH) (defined before treatment) and the woman's age both as single and combined predictors of ovarian response and pregnancy in an in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme. A total of 120 women undergoing their first cycle of IVF or ICSI was included. Forty consecutive cycles cancelled because of poor follicular response were initially selected. As a control group, the nearest completed IVF/ICSI cycles before and after each cancelled cycle (i.e. the closest cycles in temporal relationship to the index cycle) were used. Mean age and basal FSH concentrations were significantly higher in the cancelled than in the control group (P: < 0.01 and P: < 0.001 respectively), whereas basal inhibin B was significantly higher in the latter (P: < 0.05). The association of basal FSH (with an accuracy or predictive value of ovarian response of 79%) with cancellation rate was significant, independent of, and stronger than the effects of age and inhibin B (P: < 0.05). Any two or all three of these variables studied did not improve the predictive value of FSH alone. Woman's age was the only variable independently associated with pregnancy rate. It is concluded that the stronger predictors of success in patients undergoing their first IVF/ICSI treatment cycle are age and basal FSH rather than inhibin B. Basal FSH concentration was a better predictor of cancellation rate than age, but age was a stronger predictor of pregnancy rate.

Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1,186 infertile women

Objective: To investigate the effect of differences in endometrial thickness and pattern as visualized with present-day high-resolution transvaginal ultrasound equipment on the outcome of assisted reproductive treatment. Design: Prospective cohort study. Setting: Two large infertility units in university hospitals. Patient(s): The endometrial characteristics of 981 patients during 1,600 assisted reproductive treatment cycles were compared with those of 205 untreated women. In addition, abnormal echogenic patterns of the endometrium were characterized histologically in 44 patients. Intervention(s): None. Main Outcome Measure(s): Pregnancy rates. Result(s): The endometrium was significantly thinner in untreated women and women treated with IUI than in women treated with IVF or intracytoplasmic sperm injection. The exponential proliferation of the endometrium was similar in conception and nonconception cycles. The odds for a successful pregnancy were significantly lower in the presence of a thin endometrium in women treated with IUI but not in women treated with the long stimulation protocol for IVF or intracytoplasmic sperm injection. Singleton pregnancies were more common than multiple pregnancies in patients with thin endometria. Conclusion(s): The pregnancy rates of assisted reproductive procedures are influenced only marginally by the degree of endometrial proliferation, and treatment should not be canceled because of inadequate endometrial thickness.

Effect of intramural, subserosal, and submucosal uterine fibroids on the outcome of assisted reproductive technology treatment

Objective: To investigate the effect of subserosal, intramural, and submucosal fibroids on the outcome of assisted reproductive technology (ART) treatment. Design: A retrospective comparative study. Setting: A tertiary referral center for infertility. Patient(s): Treatment outcome of 106 ART cycles in 88 patients with uterine fibroids (33 subserosal, 46 intramural without cavity distortion, and 9 submucosal) was compared with that of 318 ART cycles in age-matched patients without fibroids. Intervention(s): Controlled ovarian hyperstimulation and ART. Main Outcome Measure(s): Findings on transvaginal uterine ultrasonography performed before the initiation of treatment and pregnancy and implantation rates. Result(s): The pregnancy rates per transfer were 34.1%, 16.4%, 10%, and 30.1% in the patients with subserosal fibroids, intramural fibroids, submucosal fibroids and no fibroids, respectively. The implantation rates were 15.1%, 6.4%, 4.3%, and 15.7%, respectively. Both rates were significantly lower in patients with intramural fibroids than in those with subserosal fibroids or no fibroids. Conclusion(s): Pregnancy and implantation rates were significantly lower in the groups of patients with intramural and submucosal fibroids, even when there was no deformation of the uterine cavity. Pregnancy and implantation rates were not influenced by the presence of subserosal fibroids. Surgical or medical treatment should be considered in infertile patients who have intramural and/or submucosal fibroids before resorting to ART treatment.