Endometrial receptivity: the age-related decline in pregnancy rates and the effect of ovarian function.

OBJECTIVE: To assess the effect of age and ovarian function on endometrial receptivity. DESIGN: Retrospective comparison between standard IVF and ovum donation in younger and older patients (< 40 and > or = 40 years of age, respectively). PATIENTS: In standard IVF, there were 325 transfer cycles in older patients and 1,103 transfer cycles in younger ones. In ovum donation, there were 236 transfer cycles in older patients and 222 cycles in younger women. Ovum recipients were then redivided into two groups, according to ovarian function: ovarian failure group (219 cycles) and eugonadal group (239 cycles) in patients with retained ovarian function as manifested by regular menstrual cycles and normal gonadotropins. RESULTS: In standard IVF, clinical pregnancy rates (PRs) were significantly lower in older patients (12.9% versus 23.8%, respectively). In ovum donation, clinical PRs were also significantly lower in older patients (21.2% versus 29.3%, respectively). A significantly higher clinical PR (31.1%) was noted in patients with ovarian failure, compared with both eugonadal patients undergoing ovum donation (19.7%) and standard IVF patients (21.3%). CONCLUSIONS: The decrease in endometrial receptivity with age is responsible for the higher rate of implantation failure in older women. Patients with nonfunctioning ovaries do better than eugonadal patients in ovum donation programs.

Avoidance of cancellation of potential hyperstimulation cycles by conversion to in vitro fertilization-embryo transfer.

OBJECTIVE: The study was undertaken to minimize the rate of ovarian hyperstimulation and to avoid cancellation of human treatment cycles in women treated with human menopausal gonadotropin (hMG) for induction of ovulation. SETTING: Patients were treated in the fertility clinic and in vitro fertilization unit of our institution, which is a government, university-affiliated hospital. PATIENTS: Ninety anovulatory patients were treated with hMG. Of these, 12 were at high risk for ovarian hyperstimulation. The criteria for potential ovarian hyperstimulation syndrome were rising excessive 17 beta-estradiol levels of greater than 1,500 pg/mL in the presence of multiple follicles with a mean diameter greater than 15 mm. These patients were transferred for continuation of treatment to our in vitro fertilization-embryo transfer (IVF-ET) unit. INTERVENTIONS: The patients underwent ova retrieval by the ultrasonically guided transvaginal approach. RESULTS: Of the 12 patients, 5 conceived (41.6%). Two patients had a mild ovarian hyperstimulation syndrome, and 1 had a moderate syndrome and was hospitalized for observation for 48 hours. CONCLUSION: In view of the results, we suggest that IVF-ET should be considered in cases in which ovarian hyperstimulation syndrome is imminent, rather than withhold human chorionic gonadotropin and cancelling the treatment cycle.

Intrauterine insemination before transfer of frozen-thawed embryos may improve the pregnancy rate for couples with unexplained infertility: preliminary results of a randomized prospective study.

OBJECTIVE: To evaluate whether a combination of IUI and frozen-thawed embryo transfer (FT-ET) with ovulation induction would improve the PR in couples with unexplained infertility. DESIGN: Prospective, randomized study. SETTING: In Vitro Fertilization Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): Sixty-two patients with unexplained infertility were assigned into two groups. The study group was composed of 32 women (38 cycles) who received ovulation induction followed by IUI and FT-ET. The control group was composed of 30 women (33 cycles) who received ovulation induction followed by FT-ET. INTERVENTION(S): Clomiphene citrate (CC) and hCG, IUI, and FT-ET. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) per cycle, PR per ET. RESULT(S): In the study group, the PR per cycle and per ET were 36.8% (14 of 38) and 40.6% (13 of 32), respectively. In the control group, the PR per cycle and per ET were 12.1% (4 of 33) and 14.3% (4 of 28), respectively. Statistically significant differences were found between the two groups in the PR per cycle (P=.02) and PR per ET (P=.03). No statistically significant difference was found between the groups for the stage in which the embryos were cryopreserved, the survival cleavage rates after thawing, grading of thawed embryos, and number of embryos transferred. CONCLUSION(S): In couples with unexplained infertility, the PR may be improved by combining IUI and FT-ET with ovulation induction. Performing IUI before thawing may prevent treatment cancellation in cycles with no surviving embryos.

Vertebral osteomyelitis: a rare complication of transvaginal ultrasound-guided oocyte retrieval.

OBJECTIVE: To present a case of vertebral osteomyelitis as a complication of transvaginal oocyte retrieval. DESIGN: Case report. SETTING: The IVF unit of a university-affiliated hospital. PATIENT(S): A 41-year-old woman who underwent IVF-ET treatment. INTERVENTION(S): Standard IVF-ET treatment cycles with the use of transvaginal ultrasound for oocyte retrieval and computed tomography-guided needle aspiration. MAIN OUTCOME MEASURE(S): Recovery of the patient, sequelae, and recurrence. RESULT(S): Vertebral osteomyelitis was diagnosed and treated with antibiotics. CONCLUSION(S): When severe low back pain occurs after ovum retrieval, vertebral osteomyelitis should be considered. Early diagnosis requires a high index of suspicion.

Circulating autoimmune antibodies may be responsible for implantation failure in in vitro fertilization.

OBJECTIVE: To investigate the role of autoimmune factors as a possible cause for implantation failure as manifested by chemical pregnancy after IVF and ET. DESIGN: Anticardiolipin, anti-double-stranded DNA (dsDNA), antinuclear antibody, lupus anticoagulant, and rheumatoid factor serum levels were examined in patients with chemical pregnancies and in matched controls. SETTING: An IVF unit, university-based IVF program. PATIENTS: The study group included 21 patients who had one or more chemical pregnancies and no deliveries. The control group consisted of 21 patients who had conceived and delivered after IVF-ET treatment, without any history of fetal wastage, matched for age, type and duration of infertility, and number of previous IVF cycles. RESULTS: The incidence of circulating autoimmune antibodies in the study group was 33.3% (7/21). Three patients (14.2%) were positive for anticardiolipin, two (9.5%) were positive for antidsDNA, one (4.7%) for antinuclear factor, and one (4.7%) for rheumatoid factor. Autoimmune antibodies were not detected in any of the control group. CONCLUSION: Autoimmunity may play a role in implantation failure in IVF-ET. Circulating autoimmune antibody screening is therefore recommended after chemical pregnancy.

Comparison of transmyometrial and transcervical embryo transfer in patients with previously failed in vitro fertilization-embryo transfer cycles and/or cervical stenosis.

OBJECTIVE: To compare ultrasound-guided transmyometrial and transcervical ET in patients with cervical stenosis or in patients who failed to conceive after at least three previous IVF-ET cycles. DESIGN: A prospective, randomized study. SETTING: The IVF-ET Unit at Serlin Maternity Hospital. PATIENT(S): Forty patients undergoing IVF-ET. INTERVENTION(S): Ultrasound-guided transvaginal, transmyometrial, versus transcervical ET. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Transmyometrial ET was performed in 20 patients and resulted in one clinical pregnancy. Transcervical ET, performed in another 20 similar patients, resulted in three clinical pregnancies. CONCLUSION(S): No benefit was derived by electing transmyometrial ET in preference to transcervical ET in patients who had failed to conceive in previous cycles.

Cervical dilatation during ovum pick-up in patients with cervical stenosis: effect on pregnancy outcome in an in vitro fertilization-embryo transfer program.

OBJECTIVE: To evaluate the results of cervical dilatation during an ovum pick-up session in patients with cervical stenosis who participated in an IVF-ET program. DESIGN: A retrospective study. SETTING: In vitro fertilization-ET unit. PATIENT(S): Forty-one treatment cycles in 22 patients with known cervical stenosis. In all patients previous transcervical ET had been either extremely difficult or impossible. INTERVENTION(S): Cervical dilatation under general anesthesia during an ovum pick-up session, 48 hours before transcervical ET. MAIN OUTCOME MEASURE(S): Ease of ET procedure and clinical pregnancy rate (PR). RESULT(S): Cervical dilatation was performed in 41 IVF-ET cycles and resulted in easier transcervical ET in 39 cycles, but only one clinical and one extrauterine pregnancy. CONCLUSION(S): Cervical dilatation during the ovum pick-up session leads to easier ET in patients with cervical stenosis, but PRs after this procedure are very low.

In vitro fertilization for women with pure tubal occlusion: the impact of short gonadotropin-releasing hormone agonist treatment.

OBJECTIVE: To evaluate the impact of a short GnRH agonist (GnRH-a) protocol on follicular and luteal characteristics and treatment outcome in women undergoing IVF for isolated pure tubal occlusion. DESIGN: A prospective randomized study. PATIENTS: Eighty patients with pure tubal occlusion undergoing IVF for the first time. INTERVENTIONS: Patients in group 1 (control group) were administered hMG from day 3 of the menstrual cycle. Patients in group 2 were administered 900 micrograms/d buserelin acetate intranasally from day 1 of the menstrual cycle, followed by hMG administration from day 3. Buserelin acetate was discontinued on the day of hCG administration. MAIN OUTCOME MEASURES: Information collected included E2 levels and follicular growth throughout cycle, amount of hMG required for stimulation, number of oocytes retrieved, fertilization, pregnancy, and cancellation rates. RESULTS: The short GnRH-a protocol resulted in significantly higher E2 levels and required less hMG for stimulation. However, the number of follicles aspirated, number of oocytes retrieved, fertilization rate, number of embryos transferred, pregnancy rate, and cancellation rate in both groups were comparable. CONCLUSIONS: The findings suggest that administration of a short protocol of GnRH-a to patients with pure tubal occlusion has no obvious superiority in comparison with hMG alone, except for the lower amount of hMG required for ovarian stimulation.

Elevated levels of interleukin-6 in the follicular fluid at the time of oocyte retrieval for in vitro fertilization may predict the development of early-form ovarian hyperstimulation syndrome.

OBJECTIVE: To determine the possible predictive role of interleukin-2 (IL-2), IL-6, and tumor necrosis factor (TNF-alpha) in the development of early-form ovarian hyperstimulation syndrome (OHSS). DESIGN: Nested, case-control study. SETTING: An IVF unit, university-based program. PATIENT(S): Follicular fluid (FF) was obtained from 322 high responders. The study group and control group comprised 10 patients who developed early, severe OHSS and 10 who did not develop OHSS, respectively. An additional control group included 10 low-responder patients who did not develop OHSS. INTERVENTION(S): Ovulation induction with hMG combined with GnRH analogue. MAIN OUTCOME MEASURE(S): All FF samples were tested for IL-2, IL-6, and TNF-alpha. The patient's serum was tested for mean E2 and P concentrations. RESULT(S): Interleukin-6 levels in the FF were significantly higher in the OHSS group than in the two control groups, whereas no differences were found in IL-2 and TNF-alpha. No correlation was found between the FF concentrations of IL-2, IL-6, and TNF-alpha and the mean serum E2 levels or the number of oocytes retrieved. CONCLUSION(S): Elevated levels of IL-6 in the preovulatory FF at the time of oocyte retrieval for IVF may predict the development of early-form OHSS in high responders.

Patients with Turner's syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation.

OBJECTIVE: To evaluate whether endometrial receptivity is compromised in patients with premature ovarian failure (POF) due to Turner's syndrome who undergo oocyte donation. DESIGN: Retrospective analysis. SETTING: In vitro fertilization-ET units, anonymous oocyte donation program. PATIENTS: The study included 53 patients with POF who underwent oocyte donation. These included 7 patients with Turner's syndrome (45,X) who underwent 22 ET cycles, 15 women with Turner variants (mosaics, deletions, or isochromosomes) who underwent 36 ET cycles, and 31 other patients with POF and a normal karyotype who underwent 69 oocyte donation cycles. INTERVENTION: All patients on standby for donation were treated with E2 valerate 6 mg/d until oocytes became available; then P 100 mg/d was added. Oocyte donors were healthy women < 34 years who underwent IVF themselves. MAIN OUTCOME MEASURES: Clinical pregnancy rates (PRs), biochemical pregnancies, early abortions, and delivery rates were evaluated. RESULTS: Turner's syndrome patients had a significantly higher rate of biochemical pregnancies (22.7% versus 4.3%), a lower clinical PR (22.7% versus 33.3%), a significantly higher rate of early abortions (60% versus 8.7%), and a significantly lower rate of deliveries per pregnancy (20.0% versus 73.1%) compared with non-Turner patients. CONCLUSIONS: Patients with a complete or partial deficiency of an X chromosome have reduced PRs and an increase in early implantation failure after oocyte donation. This may indicate an inherent endometrial abnormality, possibly associated with a deficiency of X-linked genes regulating endometrial receptivity.

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.

Uterine preparation with estrogen for oocyte donation: assessing the effect of treatment duration on pregnancy rates.

OBJECTIVE: To assess the effect of the duration of uterine preparation with E2 on pregnancy rates (PRs) in oocyte donation. DESIGN: A retrospective study. SETTING: IVF-ET Unit, oocyte donation program. PATIENTS: Four hundred eleven patients undergoing 865 ET cycles after oocyte donation. Uterine preparation consisted of 6 mg/d E2 valerate. The duration of treatment varied according to the availability of the oocytes for donation. Progesterone, 100 mg/d, was added upon oocyte retrieval. Patients were divided into seven groups according to the duration of uterine preparation with E2, in 5-day ranks. MAIN OUTCOME MEASURES: Pregnancy rates per ET according to the duration of uterine preparation. RESULTS: No differences were noted in the mean age, number of oocytes received, fertilization rates, or number of embryos transferred when comparing all groups. Pregnancy rates ranged from 19% to 27% for E2 treatment of 5 to 35 days. CONCLUSION: Endometrial preparation in anonymous oocyte donation programs is achieved with continuous administration of E2 until oocytes become available. Our results show that this treatment may be extended for as long as 5 weeks with no significant decrease in PRs.

High progesterone levels adversely affect embryo quality and pregnancy rates in in vitro fertilization and oocyte donation programs.

OBJECTIVE: To assess the effect of P levels on oocyte and embryo quality and pregnancy rates (PRs) in IVF and oocyte donation. DESIGN: Retrospective analysis of PRs in ovum donors and their recipients with regard to P levels on day of hCG administration. SETTING: In Vitro Fertilization Units, oocyte donation programs. PATIENTS: In vitro fertilization patients who agreed to donate oocytes were treated by hMG alone (53 cycles) or in combination with a GnRH analog (122 cycles). INTERVENTIONS: Uterine preparation in oocyte recipients consisted of 6 mg/d E2 valerate. Progesterone (100 mg/d) was added when oocytes became available. Hormonal treatment was continued until 12 weeks of gestation. RESULTS: Using a series of Fisher's Exact Tests, a critical threshold for P was identified at 1.9 ng/mL (conversion factor to SI units, 3.185). With elevated P levels (> 1.9 ng/mL), lower PRs were noted for the donors (7.1% versus 17%), as well for the recipients (8.3% versus 26.7%). CONCLUSIONS: Exposure to elevated P levels resulted in lower PRs for the donors and significantly lower PRs in the recipients. Because the endometria in the recipients were prepared uniformly, we conclude that this is the result of detrimental effects of P on oocyte or embryo quality.

Transfer of six or more embryos improves success rates in patients with repeated in vitro fertilization failures.

OBJECTIVE: To examine the results of six or more embryos transferred to patients whose IVF-ET cycles repeatedly met with failure. DESIGN: Prospective clinical evaluation of pregnancy rates and pregnancy outcome. SETTING: IVF-ET Unit. PATIENTS: Seventy-two IVF patients who had failed at least four previous IVF cycles. INTERVENTIONS: Forty-one patients (group A) received six or more embryos, and 31 patients (group B) chose to receive five embryos. MAIN OUTCOME MEASURES: Per embryo implantation rate, pregnancy rate, multiple pregnancies, and outcome were evaluated. RESULTS: With the transfer of six or more embryos, the pregnancy rate was significantly higher than with the transfer of five embryos (56% versus 29%, respectively). This was associated with a slight, but insignificant, increase in multiple gestations. No difference in pregnancy outcome was noted among the groups. CONCLUSIONS: Patients who have had repeated IVF failures may have higher pregnancy rates if six or more embryos are transferred in subsequent cycles.

Outcome of donor versus husband insemination in couples with unexplained infertility treated by in vitro fertilization and embryo transfer.

OBJECTIVE: To examine the IVF-ET outcome of couples with unexplained infertility treated by husband versus donor sperm. DESIGN: A retrospective analysis of the IVF-ET outcome of couples with unexplained infertility treated by either husband or donor sperm and in a subgroup of patients treated simultaneously by husband and donor sperm. SETTING: IVF Unit, Serlin Maternity Hospital, Tel Aviv, Israel. PATIENTS: Couples diagnosed as having unexplained infertility underwent IVF at our Unit; included were 96 couples treated by husband insemination (group A), 27 couples who received donor insemination because of azoospermia (group B), and 8 couples who sought donor insemination after having previously failed IVF (group C). RESULTS: No statistically significant difference was found between groups A and B regarding age of the females, duration of infertility, number of IVF cycles, fertilization rate, number of ETs, and pregnancy rate. Oocytes collected in group C were subdivided further into two groups: 45 were incubated with husband sperm and 46 were incubated with donor sperm. Fertilization rates were 46.6% and 50%, respectively. One pregnancy occurred. CONCLUSION: In couples with unexplained infertility who had undergone IVF-ET with husband insemination, the fertilization and pregnancy rates were similar to those of couples who were treated by donor sperm.

Multifetal pregnancy reduction: a possible risk factor for periventricular leukomalacia in premature newborns.

OBJECTIVE: To investigate the possible role of multifetal pregnancy reduction as a risk factor for the development of periventricular leukomalacia, which has been associated with prematurity and twin pregnancies. DESIGN: A case-control study. SETTING: In Vitro Fertilization Unit and Intensive Care Nursery of the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): A total of 1,401 consecutive preterm infants who were born between January 1, 1994, and December 31, 1995. INTERVENTION(S): Cranial ultrasonographic evaluation of each infant within 3 days of birth. MAIN OUTCOME MEASURE(S): Premature infants who developed periventricular leukomalacia (cases) were compared with premature infants who did not develop this disorder (controls) when multifetal pregnancy reduction was considered. RESULT(S): Fourteen premature infants developed periventricular leukomalacia. Of these, 28.6% (4 infants) were exposed to multifetal pregnancy reduction, compared with 1.9% of the controls, giving an odds ratio (OR) of 20.9 (95% confidence interval [CI] 5.5-79.4). Adjustment of this OR for IVF treatment (OR, 18.6; 95% CI, 1.8-140.3), twinning (OR, 6.3; 95% CI, 1.3-30.3), and for both IVF treatment and twinning simultaneously (OR, 8.5; 95% CI, 1.7-42.2) did not explain all the observed associations between periventricular leukomalacia and multifetal pregnancy reduction. CONCLUSION(S): Our data suggest that multifetal pregnancy reduction may be an additional risk factor for periventricular leukomalacia among premature infants, regardless of twinning.

Estrone-3-glucuronide chemiluminescence immunoassay: an alternative method for monitoring induction of ovulation with human menopausal gonadotropin in an in vitro fertilization program.

A simple, rapid, and sensitive solid-phase immunoassay procedure for the determination of estrone-3-glucuronide (E1-3-G), which uses chemiluminescence as the end point in unextracted morning urine, is described. Thirty-one patients undergoing induction of ovulation in an in vitro fertilization (IVF) unit participated in the study. From day 3 of the menstrual cycle until the day of hCG administration, morning blood samples and morning urine specimens were collected for the determination of serum 17 beta-estradiol (E2) and urine E1-3-G, respectively. A good correlation was noted between E2 measured by radioimmunoassay (RIA) and the E1-3-G measured by chemiluminescence immunoassay (CIA), from day 5 up to the day of hCG administration (0.6 less than r less than 0.85, P less than 0.001). It is evident from this study that the CIA measurement of E1-3-G in morning urine is an accurate and rapid (2.5 hours) method and is convenient for monitoring induction of ovulation with human menopausal gonadotropins.

The performance of primary and secondary unexplained infertility in an in vitro fertilization-embryo transfer program.

The term "unexplained infertility" is applied to a couple in whom after an elaborate workup no apparent reason for infertility is found. Between August 1985 and May 1987, 435 patients underwent 720 treatment cycles in an in vitro fertilization-embryo transfer (IVF-ET) unit. Eighty-three of the patients had unexplained infertility as their indication for IVF-ET. Fifty-two (group A) had primary unexplained infertility and 31 (group B) had secondary unexplained infertility. Group A underwent 87 and group B underwent 50 treatment cycles. Forty-six ET were performed in group A and 34 in group B. Clinical pregnancies were achieved in 20 patients of group A (11.5% per treatment cycle) and 13 of group B (26.0%), for a combined rate of 16.8% per cycle. Patients with tubal infertility treated in the program had a pregnancy rate of 18.8% per treatment cycle. The performance of the secondary unexplained infertility group is significantly better than that of the primary unexplained infertility group. However, the overall results with patients with unexplained infertility are similar to those patients treated for tubal infertility.

Second-trimester multifetal pregnancy reduction facilitates prenatal diagnosis before the procedure.

OBJECTIVE: To evaluate the pregnancy outcome of selective second-trimester multifetal pregnancy reduction (MFPR) compared to first-trimester MFPR. DESIGN: Cohort analysis. SETTING: In Vitro Fertilization Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): The study groups comprised 38 and 70 patients who underwent selective second-trimester MFPR (group 1) and first-trimester MFPR (group 2) at mean gestational ages of 19.7 +/- 3.3 weeks and 11.7 +/- 0.7 weeks, respectively. INTERVENTION(S): Ultrasonographically guided intracardiac injection of potassium chloride (KCl) solution. MAIN OUTCOME MEASURE(S): Pregnancy outcome and obstetric complications. RESULT(S): No statistically significant difference was found between group 1 and group 2 regarding mean gestational age at delivery (35.4 +/- 3.4 weeks and 35.9 +/- 3.1 weeks, respectively); mean birth weight (2,318.9 +/- 565.7 g and 2, 138.1 +/- 529.4 g); and the incidence of obstetric complications. These complications included pregnancy loss (5.2% and 15.7%), pregnancy-induced hypertension (0 and 10%), discordancy (12% and 18. 4%), intrauterine growth restriction (0 and 40%), and gestational diabetes (0% and 6%). However, the rate of all pregnancy complications was lower among second-trimester MFPR patients. CONCLUSION(S): Selective second-trimester MFPR is associated with favorable perinatal outcome and may facilitate detection of structural and chromosomal anomalies before the procedure and selective reduction of the affected fetus.

Hemispheric asymmetries for global and local visual perception: effects of stimulus and task factors.

Although neurotogical and physiological studies indicate a right hemisphere superiority in global processing and a left hemisphere superiority in local processing of Navon-type hierarchical letters (D. Navon, 1977), most investigations of lateralized perception in healthy participants report neither asymmetry. In 6 experiments the authors examined the influence of attentional demands, stimulus properties, and mode of response on perceptual asymmetries for global and local perception. Consistent with their theoretical predictions, asymmetries were more robust on divided- than focused-attention tasks and in response to stimuli in which local and global levels were equally salient compared with those with greater global than local saliency. Contrary to their prediction, perceptual asymmetries were not influenced by the complexity of the motor response.