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Different cumulative pregnancy rates in patients with repeated IVF- or ICSI cycles: possible influence of a male factor.

The low rate of ongoing pregnancies in IVF cycles leads to a high number of repeated cycles in couples with previously failed attempts. Therefore it would be helpful to have a prediction about the chance of becoming pregnant in a repeated cycle. In a retrospective study the data of about 4246 cycles were analysed. Because the pregnancy rates in IVF- and ICSI cycles are generally different, these two groups were distinguished between and the outcome in patients with one, two or more attempts was analysed. The rate of ongoing pregnancies per patient was lower after IVF (24.9%) than after ICSI (32.9%), but was similar or even slightly increased in patients with more than one attempt. On the other hand, there was a high pregnancy rate with ICSI in the first two cycles (35.9%), but patients with more than two ICSI cycles had a significantly lower chance of becoming pregnant (20.7%). Factors that are known to influence the pregnancy rate, such as stimulation protocol, oocyte quality or number of transferred embryos, were similar in all groups. However, significantly reduced embryo quality with successive cycles was only observed in ICSI patients. There might be a negative selection of patients with poor embryo quality and previously failed attempts after ICSI, possibly due to an andrological factor. The differences between IVF- and ICSI patients are based on treatment indications, and andrological diseases are the predominant indication for ICSI. Although no correlation was found between changes in conventional sperm parameters and number of treated cycles, there might be a subgroup of andrological patients selected by repeatedly failed ICSI cycles. Chromosomal or genetic disturbances in spermatozoa of this subgroup could be the reason for failure.

Adult↗

Sperm morphology and IVF: embryo quality in relation to sperm morphology following the WHO and Krüger's strict criteria.

BACKGROUND: The aim of this study was to examine the correlation between sperm morphology and embryo quality/IVF outcome. METHODS: The implication of sperm morphology assessment before an IVF cycle was evaluated. A total of 100 IVF couples where the female partner had either tubal factor (n=50) or unexplained infertility (n= 50) entered a prospective study, and sperm samples for the actual cycle were assessed according to the strict criteria and WHO criteria. The study was blinded for the technician involved in sperm morphology analyzing. IVF was carried out according to a long down regulation protocol using GnRH/FSH/hCG and ova were inseminated with 200,000 spermatozoa/ml. Embryos were transferred on day 2 post fertilization in a maximum of three embryos. RESULTS: No significant differences were found between the groups regarding age of the female partner (mean=34.3), no. oocytes retrieved (mean=8.5), fertilization (66.5%), pregnancies (pos. S-hCG/transfer 39.6%) or 'Take home baby rate' (birth rate/transfer 30.0%). As to the score of Krüger's strict criteria and the WHO criteria, we found no correlation between this score and cleavage rate, embryo development or pregnancies. The WHO criteria were found to be a better predictor for fertilization rate than the Krüger's criteria (p<0.002). CONCLUSION: The strict criteria or sperm evaluation according to WHO have no better predictive value for the outcome of routine IVF.

Adult↗

Danish National IVF Registry 1994 and 1995. Treatment, pregnancy outcome and complications during pregnancy.

SUBJECT: Data from the compulsory Danish National IVF Registry from 1994 and 1995 regarding treatments, abortions and complications following assisted reproductive technologies. METHODS: Data were generated through registries and compared to pregnancies in Denmark in 1995. Those pregnancies that resulted in a delivery were compared to a matched control group. RESULTS: In 1994 and 1995 5219 women were treated in 9471 initiated cycles. The numbers increased over the period. The overall delivery rate per initiated cycle was 19%, egg donation 24%, IVF 20%, ICSI 16% and frozen egg replacement 10%. The rates increased over the period. The rate of spontaneous abortions was highest for ICSI (25%) and egg donation (27%). For IVF and ICSI the birth rates per transfer of 1 embryo was 13, 1%, 2 embryos 25, 4%, 3 embryos 25, 8% and 4 or more 3, 8%. Transfer of 2 embryos resulted in 75% singleton, 25% twin and 0.2% triplet deliveries. After transfer of 3 embryos the corresponding rates were 68%, 29% and 4%. No quadruplet deliveries occurred. Totally, 1.4% reported complications to the treatment, the most frequent being ovarian hyperstimulation syndrome. In the study group 5.8% of the women who gave birth were diagnosed with imminent abortion vs. 3.0% in the control group (OR 1.98, CI 1.41-2.78). CONCLUSIONS: Transfer of three embryos did not result in higher pregnancy rates as compared to transfer of two embryos. The first data from the Danish IVF Registry support data from other registries regarding treatment, pregnancy outcome and complications during pregnancy.

Abortion, Spontaneous↗

Cetrotide confirmatory trial of cetrorelix/0.25 mg in 26 women undergoing ovarian stimulation with recombinant follicle stimulating hormones for IVF, ICSI and embryo transfer (ET).

BACKGROUND: There have been numerous double-blind, randomised, dose-finding studies of the gonadotrophin-releasing hormone (Gn-RH) antagonist Ganirelix (Org 37462) and the Gn-RH antagonist Cetrorelix. METHODS: We performed a clinical trial with 26 patients undergoing ovarian stimulation with the recombinant human follicle stimulating hormone (FSH) by applying rec. FSH in a flexible daily dose, depending on the estradiol levels of the patient, from day 3 of the cycle onwards in a controlled ovarian hyperstimulation (COH) protocol. A single dose of 0.25 mg was injected daily subcutaneously from day 7 of the cycle onwards until the day of HCG application. The recombinant FSH dose was adjusted according to ovarian response. Fifteen patients were treated for IVF and nine for ICSI. In two patients egg retrieval was not performed. Estradiol and LH levels were measured on the day of HCG application. RESULTS: The mean number of recovered oocytes in the 24 patients was 5.5. A fertilisation rate of 64% was achieved in the IVF group and 69% in the ICSI group. In Germany a maximum of three embryos per patient is permitted to be transferred. Pregnancy occurred in ten patients: 5 IVF patients and 5 ICSI patients. In this small group of IVF patients a 33% pregnancy rate per follicular puncture and a 50% pregnancy rate per embryo transfer resulted. The ICSI group showed a 55% pregnancy rate per follicular puncture and a 62% pregnancy rate per embryo transfer. CONCLUSION: Within an IVF/ET, ICSI programme the Gn-RH-antagonist Cetrorelix in combination with rec. FSH gave optimal pregnancy results.

Adult↗

GnRH antagonist in older IVF patients. Retrieval rates and clinical outcome.

OBJECTIVE: To determine if the use of a midcycle GnRH antagonist provides better clinical outcomes and lower cancellation rates in in vitro fertilization (IVF). STUDY DESIGN: We examined all patients older than 40 years undergoing IVF-embryo transfer cycles between January 1999 and December 2000. Prior to June 2000, controlled ovarian stimulation in women > or = 40 years was performed with follicle stimulating hormone (FSH)/human menopausal gonadotropin (hMG) only and no GnRH agonist or antagonist (group I). After June 2000, following the release of Ganirelix in the U.S., all women > or = 40 years were stimulated with FSH/hMG + Ganirelix (group II). Outcomes of IVF cycles prior to Ganirelix were compared to results after its introduction. RESULTS: Cancellation rates were significantly lower in group II (16%) as compared to group I (67%) (P < .05). In patients with oocytes retrieved, group II had a significantly higher number of recovered oocytes (7.7 +/- 0.8 vs. 5.3 +/- 0.7, P < .05). However, the number of embryos transferred, cumulative embryo scores, implantation rates and ongoing pregnancy rates did not differ significantly between groups. CONCLUSION: Although our results are preliminary, the addition of GnRH antagonist avoids ovarian suppression at the start of controlled ovarian hyperstimulation and prevents the premature LH surge at midcycle. Thus, more patients attempting IVF undergo oocyte retrieval, although clinical outcomes may not necessarily be improved.

Adult↗

Oocyte quality and IVF outcome after coasting to prevent ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate, in a large cohort of patients, oocyte quality and IVF outcome after coasting used to prevent ovarian hyperstimulation. SETTING: Retrospective study. PATIENTS: IVF cycles which had reached estradiol serum levels of at least 4,000 pg/mL without being coasted (control group, n = 208), or where coasting was applied (coasted group, n = 157). METHOD: IVF data of coasted cycles were compared with the control group. Within the group of coasted cycles, we also analyzed whether indirect parameters related to coasting had an effect on IVF results. RESULTS: Coasted patients showed higher maximum estradiol levels and greater numbers of large follicles than the control group, but lower oocyte recovery rates. There were no other significant differences between the two groups of patients. Within the group of coasted patients, no significant relation was found between the number of days of coasting, the estradiol level on the day of hCG, or the fall in estradiol and the outcome, whether measured in terms of oocyte quality, pregnancy rate, or incidence of ovarian hyperstimulation. CONCLUSION: Coasting seems to be associated with a reduced oocyte collection rate, especially when the coasting period is prolonged. However, this does not result in reduced oocyte quality. The length of the coasting period and degree of estradiol decrease do not seem to alter the results in terms of pregnancy rates.

Adult↗

Is recombinant follicle-stimulating hormone more effective in IVF poor responders than human menopausal gonadotrophins?

BACKGROUND: The objective of this study was to determine if the recombinant human follicle-stimulating hormone (rFSH) is more effective than human menopausal gonadotrophin (hMG) in IVF poor responders. MATERIAL/METHODS: A prospective comparative study over a 2-year period. The setting was the Tertiary IVF Center, King Faisal Specialist Hospital and Research Center. A total of 150 patients were selected from 277 patients with poor response in previous hMG-stimulated cycles who were willing to undergo another cycle of treatment. Seventy-five patients stimulated with rFSH were compared with 75 control subjects (matched for age, early follicular phase FSH, and body mass index) stimulated with urinary hMG. The number of follicles, number of oocytes retrieved, cycle cancellations, and pregnancy rates were the main outcome measures. RESULTS: There were no statistical differences in numbers of follicles (6.2 versus 5.7; p=0.97), oocytes recovered (4 versus 3.3; p=0.15), cycle characteristics, or pregnancy rates between hMG- and rFSH-stimulated cycles (p=0.32). CONCLUSIONS: Recombinant follicle-stimulating hormone (rFSH) has no advantage over urinary human menopausal gonadotrophin (hMG) on ovarian performance or the outcome of IVF-ET in poor responders' IVF cycles.

Adult↗

A double embryo transfer on days 2 and 4 or 5 improves pregnancy outcome in patients with good embryos but repeated failures in IVF or ICSI.

The purpose of this paper was to evaluate the outcome of a double embryo transfer during the same cycle for patients who had had three or more implantation failures in IVF-ET or ICSI-ET programs after the transfer of good quality embryos in all attempts. Forty-five women who had had previous unsuccessful attempts in IVF-ET or ICSI-ET programs after transfer of good quality embryos (Group A) were included in the study. Group A was divided into two subgroups, Group A1 consisted of 34 patients who underwent embryo transfer on day 2 and day 4 after pick-up and Group A2 consisted of ten patients who underwent embryo transfer on day 2 and day 5 after pick-up. Forty-two other women with a similar unsuccessful history in IVF-ET (Group B) were studied as controls. The patients in this group had a day 4 or 5 only transfer without having an additional day 2 transfer. The outcome of the procedure was compared in the two groups. Double embryo transfer had beneficial effects on patients with good embryos but with previous failure attempts. These patients had a 38.2% clinical pregnancy rate and a 50% total pregnancy rate if the additional embryo transfer was done on day 4 and a 60% clinical and 60% total pregnancy rate if the additional embryo transfer was done on day 5. Our data showed that excellent pregnancy rates can be obtained with a commercially available medium and double embryo transfers on days 2 and 4 or 5 after pick-up for patients with good quality embryos that have had previous failure attempts in an IVF-ET program. Due to the fact that endometrial maturation varies considerably in each patient, an adequate endometrial maturation and improved uterine receptivity seem to be the reason for improved pregnancy rates with double embryo transfers. It was also shown that morullae have high viability and high potential for implantation and pregnancy.

Adult↗

Treating female infertility and improving IVF pregnancy rates with a manual physical therapy technique.

CONTEXT: Infertility and pregnancy. OBJECTIVE: To assess the effectiveness of site-specific manual soft tissue therapy in (1) facilitating natural fertility and (2) improving in vitro fertilization (IVF) pregnancy rates in women with histories indicating abdominopelvic adhesion formation. DESIGN AND INTERVENTION: Pursuant to 2 promising pilot studies, 53 infertile, premenopausal patients received a 10- to 20-hour series of site-specific manual physical therapy treatments. Seventeen patients hoped to achieve a natural pregnancy; 36 planned to undergo IVF within 15 months. The primary criteria for inclusion in the studies were the inability to conceive following a minimum of 12 months of unprotected intercourse and suspected or confirmed pelvic adhesions due to abdominal and/or pelvic surgery, infectious or inflammatory disease (eg, endometriosis, PID), or trauma. Treatments were specifically designed to address biomechanical dysfunctions of the pelvis, sacrum, and coccyx and restricted soft tissue and visceral mobility due to adhesions or microadhesions affecting the reproductive organs and adjacent structures. MAIN OUTCOME MEASURES: (1) Natural fertility group: pregnancy within 1 year of therapy and subsequent full-term delivery; (2) Pre-IVF group: pregnancy (via transfer of fresh embryos from nondonor eggs) within 15 months of the last manual treatment date. RESULTS: Natural fertility group: Of the 14 patients available for follow-up (ages 25 to 44; mean, 33.5 years), 10 (71.4%) became pregnant within 1 year, and 9 (64.3%) reported full-term deliveries. Three of the 9 women who delivered reported a subsequent pregnancy, suggesting that the treatment protocol might have lasting effects. Two women have had a second live birth delivery; and the third is still pregnant. Pre-IVF group: Of the 25 patients available for follow-up (ages 28 to 44; mean, 36 years), clinical pregnancies were documented in 22 of 33 embryo transfers vs the US Centers for Disease Control and Prevention (CDC) 2001 age-adjusted expected number of 12.7 (P < .001). The estimated odds ratio for a successful pregnancy in a cycle (manual treatment: no treatment) is 3.20 (95% confidence interval = 1.55-8.4). CONCLUSIONS: The data trend across these studies suggests that this innovative site-specific protocol of manual soft-tissue therapy facilitates fertility in women with a wide array of adhesion-related infertility and biomechanical reproductive organ dysfunction. The therapy, designed to improve function by restoring visceral, osseous, and soft-tissue mobility, is a nonsurgical, noninvasive manual technique with no risks and few, if any, adverse side effects or complications. As such, it should be considered a new adjunct to existing medical infertility treatments.

Adult↗

[The effect of selected sperm characteristics on their fertilizing potential during IVF procedures].

OBJECTIVE: Basic seminological criteria were analyzed to assess a percentage of fertilized oocytes during classical IVF procedure. DESIGN: A prospective study. MATERIALS AND METHODS: One hundred fifty semen samples from patients undergoing IVF were studied. Sperm morphology in raw semen and after its selection on a density gradient (6 structural defects of a gamete were taken into consideration), sperm concentration and motility parameters according to WHO criteria were analyzed. RESULTS: Patients achieving fertilization had a significantly higher median proportion of normal forms, concentration of sperm, motility grade A, B, C and significantly lower median values for head defects, acrosomal defects, and motility grade D, than those who did not have fertilization. A marked improvement of sperm morphology after density gradient selection was also noted. Apart from significant correlations obtained for selected semen parameters with proportion of fertilized eggs, logistic regression analysis showed that the predictive value for the IVF oocyte fertilization, using normal morphology of sperm before and after selection, grade A, B and C of sperm movement in a raw semen accounted for 62.4% of fertilization. CONCLUSION: It seems that to obtain a better efficacy of IVF prognosis, functional tests have to be added to routine semen parameters.

Adult↗

Periimplantational events post-IVF.

The rate of occurrence of pregnancy following IVF-ET (in vitro fertilization plus embryo transfer) is still very low considering the advancement of human IVF technology in the last ten years. Unrecognized variation in embryo quality is oft cited as the main factor involved in this low success rate. However, the picture is probably more complex than this, involving many factors that have a bearing on the periimplantational period following transfer of IVF embryos. Six general areas are discussed in relation to their relative significance to implantation, and the concept of an interrelated continuum of periimplantational events is proposed as a prerequisite to predictably successful implantation post-IVF.

Embryo Implantation↗

[Spermatocyte antibodies in serum and follicular fluid of IVF and GIFT patients].

With a new SPAK-ELISA test system (Seratec GmbH) we determined sperm antibodies in sera of 60 IVF, 11 GIFT patients and their husbands. We evaluated sperm antibodies in sera of 12 IVF (20.0%), 3 GIFT (27%) and 3 males with normozoospermia parameters (4.2%). Compared to seronegative patients either the number of oocytes and their quality as the fertilization- and embryo transfer rate during the IVF/GIFT procedure were not affected. No intact pregnancy occurred in cases of sperm antibodies in sera. In 16.6% of all seropositive IVF patients the detection of sperm antibodies in the follicular fluids correspond to sera. We recommend to remove autologous serum for the oocyte culture in cases of sperm antibodies in serum of IVF patients.

Antibodies↗

In vitro fertilization-embryo transfer in the United States: 1988 results from the IVF-ET Registry. Medical Research International. Society for Assisted Reproductive Technology. American Fertility Society.

This is the third annual report of the U.S. Registry of in vitro fertilization-embryo transfer (IVF-ET) and related practices. The present report describes the 1988 experiences of 135 U.S. member clinics with respect to treatments and outcomes. During 1988 the clinics reported performing 22,649 ovarian stimulation cycles, with 3,508 (15%) resulting in a clinical pregnancy and 2,627 (12%) in a live delivery. Ninety-three percent of the clinics had at least one delivery, and overall a total of 3,427 babies were born. The overall live delivery rates were 12% for IVF (based on 13,647 retrievals), 21% for gamete intrafallopian transfer (GIFT) (based on 3,080 retrievals), and 20% for IVF and GIFT in combination (based on 671 retrievals). In addition to these treatments, detailed results are presented for zygote intrafallopian transfer, frozen embryo transfers, and IVF of donated oocytes.

Embryo Transfer↗

A fixed stimulation protocol for in vitro fertilization (IVF) without determinations of hormones in blood.

A new fixed schedule of ovarian stimulation for IVF was developed, which is not only simpler and easier to handle for the patients but also yields better fertilization and pregnancy rates. The period and beginning of stimulation are shifted by means of a contraceptive pill, so that stimulation can generally be started on a Sunday. The patient takes 100 mg clomiphene for 5 days and 7.5 mg prednisolone for 30 days to suppress possible exaggerated adrenal androgens; she also receives 150 IU of human menopausal gonadotropin (HMG) i.m. every other day from her family physician. From the 8th day of stimulation onwards, follicular growth is registered by daily ultrasound at the IVF center. When the dominant follicle exceeds 18 mm in diameter, 5000 IU human chorionic gonadotrophin (hCG) is given. Blood sampling for hormone estimations is not necessary, and only one sample of urine is needed for the LH estimation before hCG. In comparison to clomiphene citrate (Clomid) alone, Clomid plus HMG/FSH and HMG/FSH alone, this protocol resulted in significantly higher fertilization and pregnancy rates per follicular puncture. The rate of abortions and extrauterine pregnancies, on the other hand decreased. When comparing repetitive IVF cycles with the first IVF cycle, a significant reduction of oocytes in repetitions was found, but no difference was found in the number of fertilized eggs. The pregnancy rate, on the other hand, increased in the repeat cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Protocols↗

The role of the new reproductive technologies including IVF and GIFT in endometriosis.

In the context of the pathophysiology of endometriosis, the technology of IVF-ET and GIFT appears to offer a promising alternative for infertility associated with endometriosis in situations refractory to conventional medical or surgical therapy. The success rate of IVF with respect to follicular response, oocyte recovery, fertilization rate, and pregnancy rate in mild-to-moderate (stages I to II) disease is comparable to patients with tubal disease. However, compromise of oocyte recovery and fertilization appears to be present in severe-extensive cases (stages III to IV) implying an impairment of reproductive potential in advanced disease. In all stages of endometriosis, prior therapy, either medical or surgical, offers the best prognosis for an IVF or GIFT attempt. Surgical therapy with operative endoscopy at the time of oocyte retrieval offers a reasonable prognosis for treatment-independent pregnancy in cases of active endometriosis. The GIFT procedure bypasses an unfavorable peritoneal environment in stages I to II endometriosis without anatomic distortion or compromise of fallopian tube function. Pretreatment with GnRH analogues prior to ovulation induction is valuable in suppression of active disease as well as in inducing improved homogeneity of follicular response in IVF or GIFT cycles.

Endometriosis↗

[The evaluation of ultrasonic oocyte collection techniques for IVF-ET--comparing the transabdominal and transvaginal methods].

In order to evaluate the effectiveness and safety of ultrasonic oocyte collection for IVF-ET, a comparative study was performed on the results of IVF-ET by the transabdominal and transvaginal methods in 145 cycles of 51 patients. The oocyte collection rate for the transvaginal method was significantly higher than that for the transabdominal method (77.1% vs. 68.7% per follicle, p less than 0.01). The majority of the oocytes were collected in three follicular flushings. The fertilization rate for oocytes collected by the transabdominal method was significantly higher than that for those collected by the transvaginal method in cases of tubal damage and endometriosis (81.1% vs. 65.6% per oocyte, p less than 0.01). There was no significant difference between the signs of complications seen with the two methods. Six successful pregnancies were obtained by IVF-ET in our hospital (4 cases by the transabdominal method, and 2 cases by the transvaginal method). Two of these cases have already delivered full term healthy male infants. In conclusion, these results indicate that ultrasonic oocyte collection has been established as the most effective method for IVF-ET by means of either the transabdominal or the transvaginal methods.

Adult↗

Current ethical issues in IVF.

This article has briefly reviewed the range of public policy issues and ethical questions raised with respect to IVF. It then discussed selected issues that are now under policy debate and decision. Given the wide acceptance of IVF as a medical procedure for married couples, what variants might also be ethically defensible? IVF for unmarried couples appears defensible under specific conditions that are equally applicable to married couples. Involvement of third parties (gamete donation and gestational surrogacy) is more complex and needs case by case examination. Sperm donation appears to generate little that is ethically new when coupled with IVF but requires the same care and concern as AID. Egg or embryo donation, however, does raise new ethical questions that need close attention and continuing analysis. Freezing of human embryos also breaks new ethical ground, particularly in the options it generates beyond a narrowly defined medical domain. Certain of these options are better not undertaken without further public policy decision. Improvement of current procedures and techniques through effective clinical trials can be ethically carried out in terms of scientific and medical perspectives. However, efforts in this direction will be more effective if undertaken within a public policy framework that clearly defines acceptability during a transitional period of confidence-building.

Adoption↗

"Simplified IVF": program for developing countries.

The aim of this study is to assess the results of the "Simplified IVF" program at Ramathibodi Hospital. Ramathibodi IVF program has been in operation since October, 1991. Some steps of the conventional IVF procedures have been modified due to the limitation of resources. The embryo laboratory is a simple, clean room situated in a different building from the oocyte recovery room. Short protocol of GnRHa/HMG is used for ovarian stimulation. Monitoring of the follicular development is performed by ultrasound alone with limited number of scans (2-3 times/cycle). Oocyte retrieval is carried out under transvaginal ultrasound guidance and the aspirate transported to the embryo laboratory in a simple insulated box. Luteal phase is supported by giving micronized progesterone. Eighty five couples have undergone 105 ovarian stimulation cycles. OR was done in 100 cycles from 80 couples. Total oocytes collected is 1091. The fertilization rate is 75 per cent. Embryos were transferred in 97 cycles. Clinical pregnancy occurred in 25 cycles. Pregnancy rate per OR and ET is 25 and 25.8 per cent respectively. Nineteen patients have delivered (6 twins, 13 singletons). Simplification of procedures has enabled the IVF service to be available in a center with limited resources without compromising the results. Other advantages are improvement of the patient's convenience, cost savings and less time consumed as well as being less stressful.

Adult↗