IVF-ET Outcome Research Articles

Cycle-specific and cumulative fecundity in patients with endometriosis who are undergoing controlled ovarian hyperstimulation-intrauterine insemination or in vitro fertilization-embryo transfer

Objective: To compare controlled ovarian hyperstimulation-intrauterine insemination (COH-IUI) or IVF-ET pregnancy rates per cycle (PR) and cycle and cumulative fecundity (f and cf) with COH-IUI or IVF-ET in endometriosis. Design: Retrospective analysis. Setting: Endometriosis research institute. Patient(s): Women with endometriosis and infertility (n = 313) who underwent consecutive COH-IUI (202 patients, 648 cycles), IVF-ET (111 patients, 139 cycles), or IVF-ET after failed COH-IUI (56 patients, 68 cycles). Intervention(s): None. Main Outcome Measure(s): Crude PR and life table-estimated f and cf. Result(s): With COH-IUI, 69 patients conceived; 65 conceived with IVF-ET; and 30 conceived with IVF-ET after COH-IUI (PR 11%, 47%, and 44%). With COH-IUI, six-cycle cf was 41%, and f for cycles 1–6 was 15%, 12%, 8%, 7%, 7%, and 0. With IVF-ET, three-cycle cf was 73%, whereas f for cycles 1–3 was 47%, 27%, and 33%. First-cycle f with IVF-ET was significantly higher than cf of six COH-IUI cycles. When the data were stratified according to the stage of endometriosis and women’s age, the benefit of IVF over COH was even more pronounced. Prior COH-IUI failure did not adversely affect IVF-ET outcome. Conclusion(s): In endometriosis, PR, f, and cf are significantly higher with IVF-ET than COH-IUI, especially in stage IV and in women >38 years of age. Considering adverse effects of prolonged ovarian stimulation on endometriosis, IVF-ET should be the first-line approach in the management of infertility in this disease. If COH-IUI is attempted, it should not exceed three to four cycles.

The impact of peak follicular estradiol (E2) levels and its dramatic mid-luteal decline on the outcome of IVF-ET

Objective: Intense debate surrounds the influence of markedly elevated E2 levels at the late follicular phase and its mid-luteal decline following controlled ovarian hyperstimulation (COH) after pituitary suppression for IVF-ET (HR, 14:2777–82; 15:1903–8). Our objective was to quantify the decline in E2 levels from the day of hCG administration to the mid-luteal phase and to evaluate the impact of the absolute E2 level and its decline upon IVF-ET outcome.

Comparison of stimulation with clomiphene citrate in combination with recombinant follicle-stimulating hormone and recombinant luteinizing hormone to stimulation with a gonadotropin-releasing hormone agonist protocol: a prospective, randomized study

Objective: To compare IVF-ET outcome with a new stimulation protocol using clomiphene citrate (CC) with recombinant FSH and LH to stimulation with the standard long GnRH-a protocol. Design: Prospective randomized study. Setting: Outpatient infertility clinic in Vienna, Austria. Patient(s): Two hundred ninety-four infertile women undergoing IVF-ET; 154 IVF cycles stimulated with CC + recombinant FSH + recombinant LH (group A) and 140 cycles with long GnRH-a suppression + recombinant FSH (group B). Intervention(s): Controlled ovarian hyperstimulation, egg retrieval, and ET. Main Outcome Measure(s): Cycle parameters (number of oocytes, fertilization, number of embryos) and outcome (pregnancy rate, cancellation rate, ovarian hyperstimulation syndrome [OHSS]). Result(s): Pregnancy rate per ET was 42.9% (implantation rate, 21.3%) in group A and 36.6% (17.4%) in group B. Cancellation rates were similar. The OHSS occurred in four cases (3%) in group A and 12 cases (10%) in group B. Conclusion(s): Stimulation with CC + recombinant FSH + recombinant LH leads to comparable pregnancy rates vs. the long protocol. With this new stimulation, less gonadotropins are used and there is less need for monitoring (lower cost for patient and clinic). The risk of OHSS is reduced as well. Therefore, this protocol should be regarded as the first-line treatment.

Comparison of IVF-ET outcomes under various GnRH agonist dosages in a long down-regulation protocol

Comparison of IVF-ET outcomes under various GnRH agonist dosages in a long down-regulation protocol

Effect of long GnRH-agonist hormonal suppression on IVF-ET treatment in stage-III (moderate) or stage-IV (severe) grades of endometriosis-associated infertility

Objective: To evaluate the efficacy of prolonged gonadotropin-releasing hormone-agonist (GnRH-a) hormonal suppression on IVF-ET outcome in the patients with moderate/severe grades of endometriosis (AFS grades III & IV).

Clinical value of early cleavage embryo

Objective: This study was undertaken to see if embryo transfer containing early cleavage embryos resulted in better clinical pregnancy rate. Method: The treatment outcomes of IVF-ET were retrospectively reviewed. Out of 258 transfer cycles, 160 cycles contained no early cleavage embryos (Group I) and 98 cycles contained at least one early cleavage embryo (Group II). The definition of early cleavage embryo is the presence of two blastomeres 24–26 h after insemination. The implantation rate, clinical pregnancy rate were compared between two groups. Student's t-test and the Mann–Whitney U-test were used for continuous variables, and the Chi-squared (χ 2) test was used for binary variables. Differences were considered statistically significant at P<0.05. Result: The implantation rate and clinical pregnancy rate were 11.6% and 25.6% in Group I, 18.6% and 38.8% in Group II ( P<0.05). Conclusion: Early cleavage embryos possess greater implantation potential. Embryo transfer containing early cleavage embryos had a better clinical pregnancy rate.

Do lunar cycles influence in vitro fertilization results?

Our objective was to investigate the lunar influence on IVF-ET outcomes. Between 1992 and 1999 we have completed 7572 preprogrammed IVF-ET treatment cycles with the same stimulation protocol in two outpatient units. (Vienna, Austria and Budapest, Hungary) Multiple regression (SAS; proc Logistic) and two separate analyses were performed on pregnancy rates using a harmonic sinoidal trend based on the synodic and anomalistic lunar cycles respectively. The overall pregnancy rate was 30.9%. The amplitude of harmonic sinoidal, trend for the synodic lunar cycles was chi2 = 1.63,2d.f., p = 0.44 and chi2 = 6.27,2d.f., p = 0.044 for the anomalistic moon periods. For the anomalistic lunar months the amplitude of harmonic sinoidal trend was borderline in terms of higher pregnancy rates with the moon in Perigee. The cause of seasonal changes in IVF-ET outcomes is probably very complex. Our results indicate that lunar influence may only be one of the contributing factors. Further studies are needed to clarify unexplained fluctuations of pregnancy outcomes.

Does ovarian surgery for endometriomas impair the ovarian response to gonadotropin?

Objective: To evaluate the ovarian response to stimulation conducted for IVF treatment in women who have undergone conservative surgery for endometriomas.Design: Retrospective study with prospective selection of participants and controls.Setting: University infertility clinic.Patient(s): A series of 374 women who underwent in vitro fertilization (IVF). The study group consisted of 85 patients with ovarian endometriomas who had undergone laparoscopic surgery in an attempt to become pregnant, but had failed within a year of surgery. The control group consisted of 289 patients with tubal factor infertility.Intervention(s): IVF-embryo transfer procedures.Main Outcome Measure(s): Stimulation parameters, fertilization, implantation, and pregnancy rates were analyzed in both groups.Result(s): There was no significant difference between the two groups in stimulation parameters or IVF outcome.Conclusion(s): A total of 820 cycles were analyzed. A similar IVF-ET outcome was observed in patients with endometriosis after ablation of endometriomas compared to women with tubal factors. In conclusion, endometrioma surgery by internal wall vaporization does not impair IVF outcome. The clinical pregnancy rate was respectively 37.4% and 34.6% in the endometriosis group and the control group.

Beneficial effects of residual LH levels after GnRH agonist on ovarian response to rFSH, embryo quality, and IVF-ET outcome.

Objective: By the mid-follicular phase of the menstrual cycle, progressive LH secretion parallels the acquisition of LH receptors by the granulosa cells, a phenomenon that may assist final oocyte-follicular maturation and ovulation. In COH, GnRH agonist pretreatment often leads to extensive suppression of endogenous LH activity. By definition, defective LH activity is not subsequently compensated by FSH-only recombinant preparations and such an unbalanced endocrine milieu may alter oocyte-follicular quality. Yet, previous studies addressing this issue have led to divergent conclusions (Scott Sills et al., Hum Reprod, 1999; Fleming et al., Hum Reprod, 1998). Hence, to clarify this point, we assessed possible differences in ovarian response to COH, embryology data, and IVF-ET outcome in women having consistently low or high residual LH levels after pretreatment with GnRH agonist.

Effects of vaginal progesterone administration on uterine contractility at the time of embryo transfer

Objective: To investigate whether uterine contractility at the time of embryo transer (ET) can be reduced by early onset of luteal support with progesterone administered vaginally. Design: Prospective analysis. Setting: Assisted reproduction unit. Patient(s): Eighty-four women undergoing 84 GnRH-a and FSH/hCG cycles for IVF-ET were studied. Intervention(s): Vaginal progesterone was randomly started on the day of oocyte retrieval (group A, n = 43) or on the evening of ET (group B, n = 41). On the day of hCG administration and just before ET, 2-minute sagittal uterine scans were obtained by ultrasound and digitized with an image analysis system for assessing uterine contraction frequency. Main Outcome Measure(s): Uterine contraction frequency. Result(s): Whereas uterine contraction frequency was similar in both groups on the day of hCG (4.6 ± 0.3 and 4.5 ± 0.3 contractions per minute, respectively), only women in group A showed decreased uterine contraction frequency on the day of ET (2.8 ± 0.2 vs. 4.2 ± 0.3 contractions per minute). Conclusion(s): Vaginal progesterone administration starting on the day of oocyte retrieval induced a decrease in uterine contraction frequency on the day of ET as compared with preovulatory values. Uterine relaxation before ET is likely to improve IVF-ET outcome by avoiding the displacement of embryos from the uterine cavity.

Embryo score is a better predictor of pregnancy than the number of transferred embryos or female age

Objective: To compare the value of 17 IVF variables, including a new mean score of transferred embryos (MSTE), in predicting pregnancy rate. Design: Retrospective study. Setting: Private IVF unit. Patient(s): Women who underwent 10,000 embryo transfers. Main Outcome Measure(s): Duration of infertility, type of infertility, female age, rank of IVF attempt, type of ovarian treatment, progesterone level, sperm count, sperm motility, sperm morphology, number of retrieved oocytes, number of mature oocytes, maturation rate, number of embryos obtained, fertilization rate, number of transferred embryos, cumulative embryo score (CES), mean score of transferred embryos (MSTE), and pregnancy rate. Result(s): Outcome of IVF-ET was significantly correlated with female age, type of infertility, number of retrieved oocytes, number of mature oocytes, maturation rate, embryos obtained, fertilization rate, transferred embryos, CES, and MSTE. Multivariate analysis demonstrated that MSTE was a better predictor of pregnancy than the number of transferred embryos and female age. Conclusion(s): Embryo quality is the best predictor of pregnancy. The embryo score described herein should be used in IVF-ET programs to choose the best embryos for transfer.

Uterine Contraction Frequency at the Time of Embryo Transfer (ET) Is Correlated With Anxiety Levels

Objective: Circumstantial evidence indicates that the psychological status may impact on uterine contractility. During pregnancy, high anxiety levels have been associated with increased uterine contractility and preterm labor (Omer et al, 1988). In the non pregnant woman, uterine contraction (UC) frequency is high in a fraction of women on the day of ET which is detrimental to embryo implantation (Fanchin et al, 1998). Because the patient anxiety status has been shown to influence IVF-ET outcome (Stoleru et al, 1997), we elected to investigate the possible association between anxiety levels and UC in IVF-ET cycles. Design: Prospective study on the effects of anxiety (defined as “acute” or state anxiety and “chronic” or trait anxiety) on UC in IVF-ET. Materials and Methods: 48 women, aged 25–38, undergoing 48 GnRH-a and hMG/hCG cycles for IVF-ET were studied prospectively. Just before ET, state and trait anxiety levels were rated using standardized questionnaires (State-Trait Anxiety Inventory-STAI, which scores range from 20 to 80). Concomitantly, women underwent continuous monitoring of their blood pressure and cardiac frequency, serum cortisol levels were measured, and 2-minute sagittal ultrasound scans of the uterus were obtained with a 7.0 MHz vaginal probe (Siemens Elegra, France), and digitized with an image analysis system (IôDP, France) for the assessment of UC frequency. Three days after ET (ET+3), women underwent similar evaluation except for the trait anxiety measurement. Results: On the day of ET, overall mean trait and state anxiety scores were 40.1 ± 1.3 and 37.1 ± 1.8, respectively (mean ± SE). At ET+3, state anxiety scores did not change significantly (35.6 ± 1.5). Trait anxiety scores correlated positively with serum cortisol levels (r=0.36; P<0.02) but not with blood pressure and cardiac frequency. As illustrated, on the day of ET, UC rate correlated positively with trait anxiety scores. State-anxiety scores failed to correlate with hormones and UC on the days of ET and ET+3. Conclusion: The significant correlation between trait anxiety status and UC frequency at the time of ET provides plausible explanation for the reported relationship between high anxiety levels and poor IVF-ET outcome. These results instigate further investigation into the effectiveness of psychological care of IVF-ET patients to reduce uterine contractility at the time of ET and improve IVF-ET outcome.

Applicability of a hCG priming of unstimulated PCOS patients for improving IVM/IVF-ET outcome∗

Objective: It has been reported that the administration of hCG may become an alternative choice of treatments for improving IVF-ET outcome of unstimulated PCOS patients. This clinical study was conducted to further examine whether this system is applicable for our ART system employing different IVM/IVF/IVC programs.

New look at endometrial echogenicity: objective computer-assisted measurements predict endometrial receptivity in in vitro fertilization–embryo transfer

Objective: To determine whether endometrial echogenicity, assessed objectively by a computer-assisted system on the day of hCG administration, predicts endometrial receptivity in controlled ovarian hyperstimulation (COH) cycles for IVF-ET. Design: Prospective analysis. Setting: Assisted reproduction unit, Clamart, France. Patient(s): Two hundred twenty-one women (aged <38 years with a normal uterus and ≥2 grade A or B embryos transferred) undergoing 228 GnRH agonist and FSH/hCG cycles for IVF-ET. Intervention(s): On the day of hCG administration, uterine ultrasound scans were digitized with an image analysis system. Endometrial echogenicity was assessed as the ratio of the extent of the hyperechogenic transformation over the whole endometrial thickness. According to this, cycles were sorted arbitrarily into six groups: <30% (n = 34), 31%–40% (n = 37), 41%–50% (n = 37), 51%–60% (n = 55), 61%–70% (n = 37), and >70% (n = 28). Main Outcome Measure(s): Pregnancy and implantation rates. Result(s): The groups were similar in regard to population characteristics, ovarian response to COH, and embryology data. Pregnancy rates (59%, 57%, 35%, 20%, 16%, and 11%, respectively) and implantation rates (35%, 23%, 17%, 6%, 7%, and 3%, respectively) fell progressively and significantly from the low-echogenicity group to the high-echogenicity group. Conclusion(s): The present results confirm and extend previous observations that advanced hyperechogenic transformation of the endometrium is associated with poor IVF-ET outcome.

Impact of stage iii–iv endometriosis on recipients of sibling oocytes: matched case-control study

Objective: To evaluate the impact of severe endometriosis on IVF-ET outcome in women receiving oocytes from the same donor. Design: A matched case-control study. Setting: Oocyte donation program at the Instituto Valenciano de Infertilidad. Patient(s): Fifty-eight recipients were included in a matched case-control study of IVF-ET in our oocyte donation program. Twenty-five patients were diagnosed by laparoscopy with stage III–IV endometriosis (group I), while the remaining 33 were free of the disease (group II). On the day of retrieval, oocytes from a single donor were donated to recipients from both groups. Some of the donors supplied oocytes for more than 2 patients. Recipients received steroid replacement therapy for endometrial preparation. Intervention(s): Ovarian stimulation and oocyte retrieval in donors. Uterine embryo transfer (ET) in recipients after appropriate exogenous hormone replacement therapy (HRT). Main Outcome Measure(s): Pregnancy, implantation, miscarriage, and live birth rates. Result(s): The number of oocytes donated and fertilized, as well as the number of available and transferred embryos, was not statistically different between the two groups. Pregnancy, implantation, and miscarriage rates were not affected by stage III–IV endometriosis when compared with the control group. The live birth rate was 28.0% in the group with endometriosis and 27.2% in the control group. Conclusion(s): These results show that implantation is not affected by stage III–IV endometriosis. Given the contemporary methods of endometrial preparation for transfer of embryos derived from donor oocytes, any potential negative effect of severe endometriosis on the uterine environment is undetectable.

Effect of gonadotrophin‐releasing hormone (GnRH) antagonist during the LH surge in normal women and during controlled ovarian hyperstimulation

Several studies have suggested that GnRH is instrumental in triggering the LH surge. The present studies were performed to evaluate the effect of GnRH antagonist administration in women after the beginning of the LH surge. In study one, six normal cycling women were given a GnRH antagonist (20 mg Nal Glu s.c.) during an unstimulated cycle. Nal-Glu was administered when the LH level was higher than 10 U/l and associated with an oestradiol (E2) level higher than 730 pmol/l. In study two, a GnRH antagonist (3 mg Cetrorelix, ASTA-Medica, Frankfurt, Germany) was administered on day 8 of an IVF-ET cycle, in 157 women. Eighteen women among this cohort received the antagonist, when their LH level was higher than 10 U/l. In normal volunteers (study one), Nal-Glu was administered on day 13.7 +/- 1.4 (mean +/- SD) of the cycle when the LH level was 13.7 +/- 3.5 U/l with an E2 plasma level reaching 980 +/- 131 pmol/l. Twenty-four hours after administration of the antagonist, the LH surge had been interrupted in all subjects; it was postponed in three of the women, and abolished in the remaining three. LH levels fell by 68.5%, E2 by 42% and FSH by 53.2%. In study two, LH plasma levels 24 h after the antagonist administration fell by 94%. No premature ovulation occurred in any of the patients treated. Administering the antagonist before (n = 139) or during the LH surge (n = 18) made no statistically significant difference to the results of the IVF-ET attempt. Our results indicate that GnRH is required throughout the gonadotrophin surge in women, not only for the initiation but also for the maintenance of the LH surge. In addition, in our study, the suppression of the rise in LH, when the antagonist was given during the surge, had no detrimental impact on IVF-ET outcome. This suggests, if confirmed on a larger scale, that late follicular phase GnRH antagonist administration to prevent the LH surge in controlled ovarian hyperstimulation (COH) is a safe and useful treatment.

The significance of delayed suppression using buserelin acetate and recombinant follicle-stimulating hormone in a long protocol in vitro fertilization program

Objective: To determine whether the time taken to achieve ovarian suppression has an impact on ovarian responsiveness and the outcome of IVF-ET. Design: Retrospective analysis. Setting: An assisted reproduction unit at a university center. Patient(s): Patients undergoing a long protocol of IVF-ET that included buserelin acetate therapy initiated on day 2 of the cycle and recombinant FSH. Intervention(s): Patients were divided into two groups according to the duration of buserelin acetate therapy required to achieve pituitary and ovarian suppression (group 1 = 2 weeks, n = 172; group 2 = ≥3 weeks, n = 337). Main Outcome Measure(s): Number of recombinant FSH ampules administered, duration of ovarian stimulation (days), ovarian response, and IVF outcome. Result(s): The patients in group 2 had lower mean E 2 levels after 5 days and 9 days of stimulation than the patients in group 1. The number of recombinant FSH ampules administered and the number of days of stimulation required were higher in group 2 than in group 1. These differences were prominent in the subgroups of older patients (≥36 years) and patients who had no evidence of polycystic ovaries on ultrasound examination. The number of oocytes retrieved and fertilized, the cancelation rate, and the pregnancy rate were similar in the two groups. Conclusion(s): Prolonged administration of a GnRH agonist to achieve suppression leads to a reduced ovarian response, particularly in women ≥36 years of age, but does not affect the success rate of IVF-ET.

Patients with stages III and IV endometriosis have a poorer outcome of in vitro fertilization–embryo transfer than patients with tubal infertility

Objective: To evaluate the outcome of IVF in patients with stages III and IV endometriosis. Design: Retrospective study. Setting: The Sara Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Israel. Patient(s): Fifty-eight patients with stages III and IV endometriosis and 60 patients with tubal infertility. Intervention(s): IVF-ET for all couples. Main Outcome Measure(s): Fertilization, pregnancy, and birth rates. Result(s): The comparison between patients with endometriosis and those with tubal infertility indicated that the former had a poor IVF outcome in terms of reduced fertilization rate (40% vs. 70%), reduced pregnancy rate per cycle (10.6% vs. 22.4%), and reduced birth rate per cycle (6.7% vs. 16.6%). The differences were statistically significant. Conclusion(s): The results show an unfavorable outcome of IVF-ET in patients with endometriosis when compared with those who have tubal infertility.

Crinone 8% vaginal progesterone gel results in lower embryonic implantation efficiency after in vitro fertilization-embryo transfer

Objective: To evaluate the outcome of IVF-ET after the use of Crinone 8% (Wyeth-Ayerst Laboratories, Inc., Philadelphia, PA) vaginal progesterone gel and to compare these results with those seen in our program with the use of IM progesterone-in-oil. Design: Retrospective cohort study. Setting: A tertiary referral reproductive medicine unit. Patient(s): Patients <40 years of age undergoing IVF-ET cycles. Intervention(s): Patients were treated with either Crinone 8% vaginal progesterone gel (90 mg) administered daily or IM progesterone-in-oil (50 mg) administered daily. Main Outcome Measure(s): Biochemical pregnancy rate, implantation rate, and clinical and ongoing pregnancy rates. Result(s): The use of Crinone 8% vaginal progesterone gel was associated with a lower implantation rate (16.6% versus 26.2%; odds ratio [OR] = 0.56; 95% confidence interval [CI], 0.35–0.89) compared with the use of IM progesterone-in-oil. Biochemical pregnancies were more common after the use of Crinone 8% vaginal progesterone gel as defined by either biochemical pregnancies per transfer (15.9% versus 5.7%; OR = 3.11; 95% CI, 1.17–8.32) or biochemical pregnancies as a proportion of positive serum hCG titers (29.2% versus 9.8%; OR = 3.80; 95% CI, 1.33–10.86). Clinical pregnancy rates also were lower with the use of Crinone 8% vaginal progesterone gel (36.4% versus 52.9%; OR = 0.51; 95% CI, 0.26–0.99). Conclusion(s): Implantation efficiency is reduced, as demonstrated by lower embryonic implantation rates and higher biochemical pregnancy rates, when Crinone 8% vaginal progesterone gel rather than IM progesterone-in-oil is used for luteal phase support after IVF-ET.

P-086. Influence of sperm selection methods on recovery rate of chromatin-condensed (chromomycin A3-staining), morphologically normal spermatozoa and IVF-ET outcome

P-086. Influence of sperm selection methods on recovery rate of chromatin-condensed (chromomycin A3-staining), morphologically normal spermatozoa and IVF-ET outcome