Single versus double insemination: a retrospective audit of pregnancy rates with two treatment protocols in donor insemination

Our objective was to evaluate the effect of a change in treatment protocols, suggested following an inspection visit by the regulatory authority, from single to double inseminations during donor insemination treatment cycles. We therefore conducted a retrospective audit of pregnancy rates in the reproductive medicine clinic of a major teaching hospital. All patients were treated for male factor infertility by donor insemination, without ovulation induction with gonadotrophins between October 1992 and December 1995. The main outcome measures were cumulative conception and live birth rates. During the study period 250 patients underwent treatment and 650 single insemination and 277 double insemination treatment cycles were undertaken. The pregnancy rate per cycle was 0.054 and 0.119 for single and double insemination respectively. After six cycles the cumulative pregnancy rates were 0.28 and 0.47 and the take-home baby rates were 0.25 and 0.37 for single and double inseminations respectively. The change in practice from single to double insemination resulted in a doubling of the pregnancy rate per treatment cycle. Cumulative pregnancy rates after two treatment cycles of double insemination were comparable with those achieved after six cycles of single insemination. These results have significant implications for both patients and purchasers.     

In vitro fertilization with low-dose clomiphene citrate stimulation in women who respond poorly to superovulation

PURPOSE: Our experience with IVF using low-dose clomiphene citrate for stimulation in "non-" and "poor" responders was reviewed and the treatment outcomes with the previous controlled ovarian stimulation cycles in which hMG and GnRH agonist were used were compared. METHODS: The treatment outcome in 11 non- and 20 poor responders having 30 and 53 clomiphene citrate IVF treatment cycles, respectively, were compared with the treatment outcome in the previous long-protocol buserelin/hMG cycles. RESULTS: The clinical pregnancy rates per oocyte collection achieved in the first clomiphene citrate cycle in non (9.1%)- and poor (10%) responders were comparable to those achieved by poor responders (11.9%) who had buserelin/hMG using the long protocol. Although the numbers were small, a similar pregnancy rate could still be achieved in poor responders up to the third attempt using clomiphene citrate. CONCLUSIONS: IVF using long-protocol buserelin/hMG is more successful than using clomiphene citrate stimulation. However, this advantage may not be significant in those women with a previous poor response to buserelin/hMG. It is suggested that for such poor responders, three attempts of IVF in a clomiphene citrate cycle may offer a viable therapeutic alternative before reverting to more stressful, expensive, and time-consuming treatment.     

Comparison of the cumulative probability of pregnancy after in vitro fertilization-embryo transfer by infertility factor and age

OBJECTIVE: To compare the cumulative probability of pregnancy after multiple IVF cycles by age and cause of infertility. DESIGN: A prospective study was done in which patients were followed from the time they registered for their first IVF cycle until they achieved a clinical pregnancy, withdrew from treatment, or study was terminated. PATIENTS, SETTING, TREATMENTS: Infertile women undergoing IVF-ET at the Cooper Institute for In Vitro Fertilization were enrolled in this study if the luteal phase leuprolide acetate (LA) and hMG controlled ovarian hyperstimulation (COH) regimen was used. MAIN OUTCOME MEASURES: Clinical pregnancy, as determined by a positive beta-hCG level and ultrasonographic confirmation of a gestational sac, and delivery rates based on number of women with live births were compared by infertility factor and age. RESULTS: The 3-month cumulative probability of pregnancy based on life table analysis was 33% in women with tubal factor who were < or = 35 years of age, 25% in women with tubal factor who were > 35 years of age, 30% for women with multiple factors who were < or = 35 years of age, and 14% for women with multiple factors who were > 35 years of age. The rate for the older women with multiple factors was significantly lower than that for the other groups. The delivery rates were lower for the women with multiple factors than for women under 35 with tubal factor only. CONCLUSIONS: There is a significant effect of age and infertility factor on pregnancy and delivery rates. Physicians should consider these factors in evaluating their patients' prospects for success in IVF-ET.     

Reparation activity and neurogenesis

OBJECTIVE: To study the outcome in poor responders to three ampules (225 IU) of hMG per day in subsequent IVF treatment cycles in which six ampules (450 IU)of hMG per day were administered. DESIGN: Retrospective chart review. SETTING: Academic tertiary center. PATIENTS: Between January 1988 and May 1995, 126 poor response patients had a first treatment cycle on three ampules and a second cycle on six ampules of hMG per day. MAIN OUTCOME MEASURES: Numbers of follicles, oocytes, and embryos, and pregnancy rates. RESULTS: On six ampules, patients had significantly more follicles and oocytes. The number of embryos did not differ significantly. The pregnancy rate on six ampules were low (3.2% pregnancies per cycle started). CONCLUSION: Poor responders do not benefit from high-dose hMG stimulation; their reproduction outcome is poor.     

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

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

Chronic hepatitis C in children: a clinical and immunohistochemical comparative study with adult patients

A retrospective analysis of clinical and laboratory data was made of all in-vitro fertilization (IVF) patients with tubal pathology who had their first ever embryo transfer cycle between January 1st, 1992 and September 1st, 1996. The aim of the study was to determine the effect of the presence of a hydrosalpinx, whether or not visible by ultrasound, on pregnancy, multiple pregnancy and implantation rates in our patient population. The IVF success rate was also analysed by calculating cumulative ongoing pregnancy rates of the same patient group using the lifetime table approach. In the presence of an ultrasound-visible hydrosalpinx, rates of pregnancy and multiple pregnancy appeared reduced, but the differences were not significant. The rates of implantation, clinical implantation and ongoing implantation were significantly lower in the presence of an ultrasound-visible hydrosalpinx (odds ratios 0.33-0.46, C.I. 0.21-0.96). The cumulative chance of achieving an ongoing pregnancy after one or more IVF cycles was significantly reduced in the presence of an ultrasound-visible hydrosalpinx (relative hazard 0.36, C.I. 0.22-0.59). In the presence of a hydrosalpinx not visible by ultrasound the IVF outcome was not reduced. This retrospective study confirms that patients with hydrosalpinges have an impaired IVF outcome. Unique to this study and previously unobserved is the finding that there is a subgroup of patients with hydrosalpinges, those with ultrasound-visible hydrosalpinges, which is exclusively responsible for this impaired outcome.     

The mechanism of decrease in dynamic mitral regurgitation during heart failure treatment: importance of reduction in the regurgitant orifice size

There are numerous studies concerning pregnancy rates in oocyte donation, yet only a handful report the obstetric outcome in such pregnancies. The purpose of this study was to assess factors that influence pregnancy rates, to determine the incidence of complications, and to evaluate obstetric outcome in pregnancies resulting from oocyte donation. This study included 423 oocyte recipients who underwent 1001 oocyte donation cycles at the Oocyte Donation Programme, In-Vitro Fertilization (IVF)-Embryo Transfer Unit, Herzlia Medical Center, Israel. Donors were all healthy women < 34 years old who underwent IVF themselves. In 873 cycles, fertilization occurred and embryo transfer was performed, resulting in 194 clinical pregnancies. Pregnancy rates (PR) significantly declined with the increase in number of previous attempts, and with increasing age of recipient (36.8%/embryo transfer in patients < or = 30 compared to 17.8% in patients > 40 years old). A significant increment in PR was noted with the increasing number of embryos transferred. The overall PR was 22.2%/embryo transfer. However, in young amenorrhoeic patients with normal karyotypes undergoing their first cycle, PR was 52.2%; the 'take home baby' rate was 38.3% per patient undergoing embryo transfer and 17.8% per embryo transfer cycle. A significant increase in the incidence of pregnancy-induced hypertension and a higher proportion of abortions were noted in older patients. A significantly higher incidence of prematurity and low birthweight was observed in multiple pregnancies.     

Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro fertilization and embryo transfer cycle

Increased antiphospholipid antibody prevalence has been demonstrated by a number of recent studies in in-vitro fertilization (IVF) patients but the potential effects of antiphospholipid antibodies on the different components of the reproductive process and the consideration of whether to test IVF patients for antiphospholipid antibodies are controversial. The present study was undertaken to investigate the possible association between the presence of circulating antiphospholipid antibodies (namely the lupus anticoagulant and anticardiolipin antibodies), among a series of 21 consecutive IVF patients having a clinical spontaneous abortion after their first embryo transfer. As a control group (n=42), the nearest IVF cycle resulting in an ongoing pregnancy before and after each miscarried IVF cycle (i.e. the closest cycles in temporal relationship to the index cycle) was used. One patient (4.8%) in the study group and two women (4.8%) among controls were seropositive for antiphospholipid antibodies. These low and similar seropositivity rates found in the two groups studied lead us to conclude that antiphospholipid antibodies testing in IVF patients should be considered only in those women having repeated failures of implantation/clinical abortion after embryo transfer but not in an infertile general population reaching an IVF programme.     

Implications of complete fertilization failure after intracytoplasmic sperm injection for subsequent fertilization and reproductive outcome

With the introduction of intracytoplasmic sperm injection (ICSI), couples with severe male factor infertility have achieved fertilization and clinical pregnancy rates comparable to other in-vitro fertilization (IVF) patients. However, failure of fertilization still occurs in some patients despite the utilization of microsurgical sperm injection techniques. How such fertilization failure after ICSI might impact later ICSI treatment(s) is unknown. In this investigation, couples with complete fertilization failure after ICSI treated from August 1993 to August 1996 were identified (index cycle, n = 21). Additionally, fertilization data from any previous or subsequent infertility treatments were evaluated. Seven patients (33%) had at least one IVF treatment before the index cycle, although no deliveries occurred. Of patients with complete fertilization failure in the index cycle, 48% (n = 10) underwent at least one subsequent ICSI cycle which proceeded to oocyte retrieval. The remainder (n = 11) elected to discontinue treatment. Although six subsequent cycles were cancelled due to poor follicular response (< or = 2 mature oocytes), all patients electing to continue treatment eventually achieved a subsequent embryo transfer. The clinical pregnancy rate per transfer was 45.4% for this group; the delivery and ongoing pregnancy rate per transfer was 36.3%. Review of semen parameters, superovulation characteristics or other clinical parameters during the three study cycles (pre-index, index, and post-index) was not prognostic of fertilization success or reproductive outcomes in later treatments. Fertilization failure with ICSI therefore could not be predicted by prior cycle performance, although total immotility of spermatozoa at time of oocyte retrieval, total teratozoospermia, and low oocyte yield were common characteristics of couples experiencing complete fertilization failure with ICSI. These findings suggest that fertilization failure in one ICSI cycle does not preclude successful fertilization and delivery in a later ICSI treatment.     

Assisted hatching of embryos by micromanipulation for human in vitro fertilization: UAMS experience

In vitro fertilization and embryo transfer (IVF) is utilized as a treatment for infertile couples who cannot conceive with standard therapy. Assisted hatching (AH) is a procedure whereby an opening is made in the zona pellucida of the embryos, thereby increasing the probability of implantation and pregnancy. AH is beneficial in patients with elevated FSH levels, older than age 38 or those who failed IVF repeatedly. Success rates after IVF with AH at the University of Arkansas for Medical Sciences (UAMS) compares favorably with rates achieved by other centers in the USA. Pregnancy rates after IVF with AH in patients older than 38 years is approximately 20% compared to a pregnancy rate of 10% in patients who did not have AH. This report summarizes the UAMS experience with IVF and AH.     

In vitro fertilization versus tubal surgery: is pelvic reconstructive surgery obsolete?

OBJECTIVE: To compare the results of pelvic reconstructive surgery with cumulative success rates of IVF for couples with tubal factor infertility. DATA RESOURCES: Outcomes of pelvic surgery were obtained from a review of articles from the literature identified by directed Medline searches. Cumulative pregnancy rates of 771 couples with tubal factor infertility treated at the Cornell IVF program between December 1989 and December 1992 were calculated by life-table analysis. RESULTS: Overall delivery rate per transfer for patients with tubal factor was 28.9% (303 deliveries per 1,048 transfers) and did not appear to be affected significantly by the presence of a secondary diagnosis. A significant decline in pregnancy rates was observed with advancing age: age < 30 years, 48.4%; 30 to 34 years, 44%; 35 to 38 years, 28%; 39 to 40 years, 20%; 41 to 42 years, 9%; and > 42 years, 4.3%. Cumulative pregnancy rates for cycles 1 to 4 were 32%, 59%, 70%, and 77%, respectively, in patients with only tubal factor, and 28%, 55%, 62%, and 75% in patients with tubal combined with other associated infertility factors. CONCLUSIONS: Our experience suggest that > 70% of women with tubal factor infertility will have a live birth within four cycles of treatment with IVF. These results compare favorably with the best outcomes after tubal reconstructive surgery. In older women, because of the rapid decline of fertility potential with advancing age, efforts should be directed toward the treatment method that provides the highest likelihood of success within the shortest time interval.     

The outcome of in-vitro fertilization treatment by egg donation and intracytoplasmatic sperm injection for severe male factor infertility: a preliminary report

Due to a paucity of donated eggs, we have excluded, until recently, couples with severe male factor infertility from our egg donation programme, except for those who accepted insemination with donor spermatozoa. The purpose of this study was to assess the feasibility of a shared in-vitro fertilization (IVF)-embryo transfer treatment whenever the recipients have severe oligoasthenoteratozoospermia (OTA) and need intracytoplasmic sperm injection (ICSI) for egg fertilization. The results from 163 consecutive couples with ovarian failure who underwent 273 cycles of IVF with donated eggs and augmented with ICSI were analysed. The rate of diploid fertilization was 54.7%; in 92.3% of the cycles, at least one embryo was available for transfer. Forty-seven clinical pregnancies were achieved, representing 18.6% conceptions per transfer. The highest pregnancy rate was achieved in menopausal patients aged 40-45 years (26.2% per cycle) and the lowest in patients >45 years old (10.8% per cycle, P = 0.03). Overall, 28.8% of the couples achieved a clinical pregnancy. A total of 196 treatment cycles resulted in 46 clinical pregnancies (23.5%) among the donors. No statistical differences were found in pregnancy rate achieved by the donors when compared with the recipients. We conclude that ICSI with egg donation is a reliable treatment in patients with ovarian failure and severe OTA.     

Transfer of cryopreserved embryos improved pregnancy rates in patients with damage to the functional integrity of the sperm membrane as measured by the hypo-osmotic swelling test

OBJECTIVE: To compare the pregnancy rates (PRs) after transfer of cryopreserved embryos in patients who have damage to the functional integrity of the sperm membrane as measured by the hypo-osmotic swelling test to those without this defect. DESIGN: Prospective clinical study. SETTING: University-associated IVF center. PATIENTS: Fifty-four patients enrolled in a matched prospective study to evaluate the effects of low HOS scores (<50%) on PRs after IVF-ET were followed to determine the PR after transfer of cryopreserved embryos. MAIN OUTCOME MEASURE: Clinical PRs and implantation rates. RESULTS: Fourteen patients with low hypo-osmotic swelling test scores underwent 21 frozen ET cycles, achieved for clinical pregnancies for a PR per cycle of 19.0% and an implantation rate of 7.1%. Twelve patients with normal hypo-osmotic swelling test scores underwent 21 frozen ET cycles, achieved five preganancies for a clinical PR per cycle of 23.8% and an implantation rate of 9.3%. CONCLUSION: Previous studies have demonstrated an adverse effect of low hypo-osmotic swelling test scores on PRs after IVF-ET despite normal fertilization. This adverse effect was not found in the transfer of cryopreserved embryos from males with hypo-osmotic swelling test scores. Further investigation is required to determine how cryopreservation improves the chances of implantation of these embryos.     

Natural cycle in vitro fertilization-embryo transfer at the University of Ottawa: an inefficient therapy for tubal infertility

OBJECTIVE: To describe our experience with natural cycle IVF making clinical and endocrine comparisons with our standard stimulated cycle IVF program. DESIGN: We attempted 75 natural IVF-ET cycles with hCG given to preempt the LH surge and compared these with 450 attempts at standard superovulation IVF-ET done in our unit during the same time period. PATIENTS: Natural cycle patients are normally ovulating women < age 38. Superovulation IVF-ET patients are all < 41 years old. Patients in both groups had partners with normal semen parameters and tubal factor infertility. MAIN OUTCOME MEASURES: Cancellation rates, pregnancy rates per egg retrieval, per ET procedure, and luteal phase E2:P ratios of the treatment cycles are compared. RESULTS: There were 35 of 75 (47%) natural cycle and 112 of 450 (25%) superovulation cycle cancellations. An egg was retrieved in only 24 of 40 (60%) natural cycles and 336 of 338 (99%) superovulation egg retrieval procedures. Pregnancy rates per ovum pick-up procedure were significantly higher: 65 of 338 (19%) in the superovulation versus 2 of 40 (5%) in the natural cycle groups. Pregnancy rates per ET were not significantly different between natural IVF-ET, 2 of 18 (11%) and superovulation IVF-ET, 65 of 298 (22%). The E2:P ratios 5 days after ET were similar in both groups at 18 +/- 4 after natural IVF-ET and 21 +/- 18 after superovulation IVF-ET. CONCLUSIONS: [1] Cancellation rates for natural cycle IVF are very high. [2] Midluteal E2:P ratios are the same in both groups. [3] Pregnancy rates per egg retrieval are significantly lower for natural versus superovulation IVF-ET. [4] In our experience, natural cycle IVF-ET is an inefficient therapy for tubal infertility compared with superovulation IVF-ET.     

Continuing the debate on empty follicle syndrome: can it be associated with normal bioavailability of beta-human chorionic gonadotrophin on the day of oocyte recovery?

This paper describes our experience with four ovarian stimulation in-vitro fertilization (IVF) cycles in which we failed to retrieve oocytes despite normal bioavailability of beta-human chorionic gonadotrophin (beta-HCG) in patients' blood 35 h after HCG administration. In three cases, the oocyte recovery procedure was interrupted, a second dose of HCG was administered and 24 h later mature oocytes were collected from two of the patients. In the first case, the three metaphase II oocytes collected fertilized after intracytoplasmic sperm injection (ICSI) and two cleaved grade three embryos were transferred but pregnancy did not ensue. In the second case, six out of eight metaphase II oocytes fertilized and cleaved following ICSI, leading to transfer of one grade two and two grade three embryos. This resulted in a clinical pregnancy which at the time of this report is ongoing. A similar rescue protocol was used for the third case who had empty follicle syndrome (EFS) in her previous treatment cycle but only cumulus-corona complexes were aspirated. Five additional patients who had EFS before instituting pregnancy diagnostic test screening have had further treatment cycles in which oocytes were collected but pregnancy did not ensue. We conclude that normal bioavailability of beta-HCG on the day of oocyte recovery does not exclude the diagnosis of EFS. EFS does not predict a reduced fertility potential in future cycles, although it may recur due to a biological abnormality in the availability of mature oocytes that are retrievable. In such patients, oocyte donation may offer the chance of achieving a pregnancy.     

Strategies in frozen donor semen procreation

Data were analysed from 710 couples who had been assessed to determine the effectiveness and the drawbacks of three different methods of insemination using frozen donor semen. Intracervical insemination (ICI) was the first method used when the women had no tubal disorder: 255 pregnancies were achieved in a total of 2558 cycles (10%). Intrauterine insemination (IUI) associated with ovarian stimulation resulted in 152 pregnancies over 966 cycles (16%). In-vitro fertilization (IVF) was proposed after approximately 12 insemination failures using either of the other methods or when the initial gynaecological examination had revealed abnormalities such as tubal occlusions; 48 pregnancies were obtained in 262 cycles (18.3%). The pregnancy rate using ICI was significantly higher when two inseminations were performed per cycle, compared with one insemination per cycle (12.3 versus 7%, P < 0.001). The number of motile spermatozoa per straw was correlated with the pregnancy rate when using ICI, rising from 9% with < 4 x 10(6) motile spermatozoa to 13.8% with 4-8 x 10(6) and 17.2% with > 8 x 10(6). No relationship was found between the number of motile spermatozoa and the pregnancy rate using IUI and IVF. The incidence of primary ovulatory disorder was higher among women whose husbands were oligozoospermic than among those whose husbands were azoospermic (19 versus 9%, P < 0.01), but ovarian stimulation improved the fecundity of subfertile women. The outcome of pregnancies was also analysed for the three methods. From these data, strategic plans have been proposed to maximize the pregnancy rate for women undergoing therapeutic donor insemination with frozen semen.     

Electroejaculation and assisted fertility in men with psychogenic anejaculation

OBJECTIVES: To evaluate sperm characteristics and fertility potential in ejaculates obtained after electroejaculation in men with psychogenic anejaculation. DESIGN: Retrospective clinical study. SETTING: In Vitro Fertilization Unit, Bikur Cholim Hospital, Jerusalem, Israel. PATIENTS: Twenty men with psychogenic anejaculation who underwent 55 sessions of electroejaculation and their spouses. INTERVENTIONS: Electroejaculation, assisted reproduction technologies. MAIN OUTCOME MEASURES: Semen analysis, IVF, intracytoplasmic injection (ICSI), fertilization rates, and pregnancy rates. RESULTS: In all patients, sperm density and motility rates were unsatisfactory (98 +/- 127 x 10(6) with 14.6% +/- 15% motility in the antegrade portions and 42 +/- 42 x 10(6) with 9.7% +/- 15.6% motility in the retrograde samples). Intrauterine inseminations performed in eight couples did not result in a pregnancy. Four couples underwent IVF-ET treatments. Two pregnancies were achieved with overall success rates of 22% per cycle. Five couples were treated using the ICSI procedure. Although good quality embryos were transferred, none of the treatments resulted in a pregnancy. CONCLUSIONS: Psychogenic failure to ejaculate may be treated by electroejaculation. However, the average motility of the sperm obtained is diminished. The combination of electroejaculation with IVF, including the ICSI procedure, should improve chances of fertilization and pregnancy in these cases.     

Sub-zonal insemination for extreme male factor infertility

When in-vitro fertilization (IVF) is used for severe male infertility, the zona pellucida constitutes a major barrier to sperm-oocyte interaction, a barrier that may, in principle, be overcome by micro-injecting one or more spermatozoa into the sub-zonal perivitelline space ('sub-zonal insemination' or SZI). We have defined suitable patients for SZI as having 'extreme' male factor in that they have either shown a failure of fertilization in previous IVF cycles or had < 50 000 motile spermatozoa recoverable after semen preparation. (This is distinct from those with only 'severe' male factor in whom sufficient (> 50 000) motile spermatozoa could be recovered from a semen preparation.) A total of 213 SZI cycles were performed at Sydney IVF in the 4 year period September 1988 to September 1992, for extreme male factor patients with previous IVF failures or extremely low sperm numbers for whom SZI was the first option (about two-thirds and one-third of cases respectively). A total of 138 embryo transfers are reported, producing 20 clinical pregnancies after performing SZI on 1899 oocytes. One patient miscarried at 12 weeks gestation and there have been nine normal deliveries (so far) of 10 healthy infants. The first delivery was in February 1990. One pregnancy was achieved in the only patient in whom spermatozoa were obtained by epididymal aspiration, and transfer of three cryopreserved embryos in another patient resulted in a singleton pregnancy. Of the 492 oocytes fertilized, 282 had two pronuclei (57.3%) and normal embryos were transferred in 138/213 (64.8%) treatment cycles, giving an overall pregnancy rate of 14.5% per embryo transfer or 9.4% per cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

External validation of prognostic models for ongoing pregnancy after in-vitro fertilization

This study aimed to validate prognostic models for predicting ongoing pregnancy after the first and second in-vitro fertilization cycles. Models were developed using data from the University Hospital, Nijmegen, 1991-1994 and tested using more recent data from the same centre and data from two other centres. Although the variables included in the models seemed plausible, the predictions of the models were unsatisfactory. The models did not discriminate between women who had achieved pregnancy and women who did not achieve pregnancy; neither could they indicate which women had a (very) low probability of ongoing pregnancy. Taking into account the success rate of a specific clinic or the success rate during a specific period did not show any advantage. The predictions were even inaccurate in the same hospital during another period. It is obvious that these prognostic models should not be used. This study shows the importance of validating prognostic models before their implementation in clinical practice.     

Focal nodular hyperplasia in a young female

OBJECTIVE: To analyze data from a large multicenter study to determine whether pregnancy and delivery rates decrease with repeated IVF-ET cycles. DESIGN: Multicenter retrospective study. SETTING: Participating centers from the Society of Assisted Reproductive Technology. PATIENT(S): Fifty-four centers contributed 4,043 cycles of oocyte retrieval for uterine transfer. INTERVENTION(S): Oocyte retrieval for uterine transfer. MAIN OUTCOME MEASURE(S): Pregnancy and delivery rates, analyzed according to age, program success rate, and whether the program was doing assisted hatching. RESULT(S): Pregnancy and delivery rates for cycles 1, 2, 3, 4, and >4 were 33.7% and 27.0%, 33.9% and 27.4%, 28.9% and 23.4%. 25.9% and 16.1%, and 21.0% and 15.4%, respectively. The pregnancy rate decreased significantly for >4 cycle; delivery rate decreased significantly for cycles 4 and >4. Assisted hatching was strongly related to better odds of pregnancy (OR, 1.50) and delivery (OR, 1.44) in women under age 40, and for pregnancy (1.64) in women age 40-42 years. CONCLUSION(S): Success rates do not decrease markedly with repeated IVF attempts, and the decrease did not change with program success rate, suggesting the IVF population is not markedly heterogeneous. Uncontrolled studies of new treatments for cycle repeaters cannot assume that success rate is poor without a treatment change.