David Kreiner

In vitro fertilization and embryo transfer (IVF/ET): An established and successful therapy for endometriosis

The purpose of this report is to present a 6-year experience in the management of endometriosis with in vitro fertilization and embryo transfer (IVF/ET). We divided 136 patients who underwent 280 cycles into three groups: (1) previous history of endometriosis but normal pelvis at the time of oocyte retrieval, (2) stages I–II endometriosis (revised AFS classification), and (3) stages III–IV endometriosis. The stimulation protocols, estradiol (E2) responses, and distribution of terminal E2 patterns were similar in all groups. Group 3 had significantly fewer preovulatory and immature oocytes retrieved and fewer embryos transferred. The fertilization rate and the per cycle/per transfer pregnancy rates were similar in all groups. The miscarriage rate was higher in group 3, and the on-going pregnancy rate per cycle was lower, Luteal phase E2 and progesterone levels were comparable in all groups. No differences were found when groups 2 and 3 were analyzed for the presence of one or two ovaries or the presencelabsence of ovarian endometriosis. The overall fertilization rate, the per cycle/per transfer pregnancy rates, and the miscarriage rate were similar to those of tubal factor patients. We underscore the excellent out-come of patients with minimal or mild endometriosis in IVF/ET. We conclude that patients with moderate or severe endometriosis have a compromised reproductive potential, probably because of a reduced oocyte recovery rate and poor embryo quality.

Correlation of follicular diameter with oocyte recovery and maturity at the time of transvaginal follicular aspiration

Forty-four consecutive patients undergoing transvaginal follicular aspiration for in vitro fertilization underwent ultrasonic measurement of follicular diameter at the time of oocyte retrieval to determine the correlation of follicular size with recovery rates and oocyte maturity. Based on the results of 412 follicles aspirated, the data were grouped by size (≤11, 12–14, 15–17, 18–20, and ≥21 mm) and oocyte maturity. Recovery rates were significantly higher in 18- to 20-mm follicles (P<0.01) and lower in those ≤11 mm (P<0.001). The probability of retrieving a metaphase I or II oocyte was significantly lower in follicles ≤11 mm (P<0.001), somewhat higher in 12- to 14-mm follicles (P<0.01), and equally high among the other groups. There were no differences in the incidence of fractured zonas. We conclude that follicles ≥15 mm provide the highest probability of retrieving mature oocytes and the low recovery rates of mature oocytes from follicles ≤11 mm suggest that, in selected circumstances, the operating surgeon may choose not to aspirate them.

Transdermal estrogen replacement in ovarian failure for ovum donation

This study examined the efficacy of transdermal estradiol (TE 2 ) replacement versus oral estradiol (OE 2 ) through evaluation of peripheral steroid levels, endometrial morphology, and clinical outcome in six patients with ovarian failure. Patients were begun on sequential E 2 and progesterone replacement with transdermal E 2 patches. Endometrial biopsies were done on day 21 of the first replacement cycle and day 26 of the second cycle. Controls were 28 cycles on a regular 28-day micronized OE 2 protocol. No significant difference was found between E 2 levels throughout the cycle of the two respective stimulation protocols, except for days 12 to 14, when the OE 2 protocol produced significantly lower E 2 than did the TE 2 protocol ( P 1 ) and E 2 values in the OE 2 group (r = 0.92) ( P 2 administration, El was significantly higher than E 2 ( P 1 was not found to be higher than E 2 in the TE 2 group, resulting in a significant difference in the E 2 /E 1 ratio of 1.59 ± 1.6 for TE 2 compared with 0.13 ± .04 for OE 2 ( P 2 revealed glandular components that were dated as day 18.2 ± 1.7, while the stroma was dated as day 21.8 ± 0.8, a statistically significant disparity ( P 2 , the same significant 3-day glandular/stromal disparity was observed ( P 2 and OE 2 groups, respectively. Embryo transfer was performed in six cycles in patients on TE 2 . A viable intrauterine pregnancy was confirmed in three of the six. It would appear that TE 2 is comparable to OE 2 as an agent for estrogen replacement for donor egg recipients with premature ovarian failure.

Spontaneous and Pharmacologically Induced Remissions in Patients With Premature Ovarian Failure

To determine the fertility potential of patients with apparent ovarian failure, a retrospective analysis of 86 ovarian failure patients in the Norfolk oocyte donation program was performed. None of the 23 patients with primary ovarian failure ovulated. Seven of 63 (11.1%) with secondary ovarian failure did ovulate, and three of 63 (4.8%) conceived and delivered normal, healthy infants. Of patients whose etiology for ovarian failure was partial ovarian resection or chemotherapy, the ovulation rate and pregnancy rate were 30.8 and 15.4%, respectively, compared with 5.0 and 1.7%, respectively, for the other patients with secondary ovarian failure. Serum estradiol and FSH obtained during hormone replacement were not predictive of the resumption of normal reproductive functions. Therefore, it is recommended that patients with secondary ovarian failure, especially in the better-prognosis group, be treated with a trial of estradiol replacement and have close monitoring for ovulation before oocyte donation.

β-Human chorionic gonadotropin as a monitor of pregnancy outcome in in vitro fertilization-embryo transfer patients

Serum human chorionic gonadotropin (hCG) was studied to test its predictability of pregnancy outcome in in vitro fertilization (IVF) patients. The mean +/- standard deviation of serum hCG concentration related to the day complete clearance of exogenous hCG was derived from 47 single term pregnancies as a normal range. This range can be used to predict spontaneous abortion (77%), multiple pregnancy (60%), and abortion in multiple-sac pregnancies terminating in the birth of fewer infants than the initial number of sacs (80%). The results also showed that our stimulation protocol did not affect the clearance rate and doubling time of endogenous hCG or implantation time as suggested by the time of endogenous hCG detection and that spontaneous abortion may be due to late implantation.

The value of in vitro fertilization for the treatment of unexplained infertility

In 54 patients referred with the diagnosis of unexplained infertility (UI), the diagnosis was confirmed in 26 (strict UI) (48%). Minimal abnormalities (MA) were found in 19 (35%); 9 (17%) had gross abnormalities and were excluded from analysis. Fifty patients with tubal infertility were randomly assigned to form a control group. Mean age and type of stimulation did not differ in the two groups. Peak follicular estradiol (E2) and terminal follicular E2 patterns were comparable. There was no difference in the mean number of oocytes retrieved per cycle. However, the control group had significantly more preovulatory oocytes: 3.6 +/- 2.0 standard deviations versus 2.8 +/- 2.1 in the overall UI group (strict UI + MA groups) and 2.7 +/- 2.2 in the strict UI group. Significantly more fertilized oocytes per cycle were obtained in the control group (P less than 0.05). The per-cycle and per-embryo transfer (ET) pregnancy rates were 32.4 and 37.3% in the overall UI group and 24 and 24.5% in the control group. The miscarriage rate was 12% in the strict UI group, 22% in the overall UI group, and 25% in the control group. It is concluded that patients with UI constitute a favorable group for in vitro fertilization and ET.

A prospective randomized comparison of single- and double-lumen needles for transvaginal follicular aspiration

Patients undergoing ultrasound-directed transvaginal follicular aspiration in a large in vitro fertilization (IVF) program were randomized for retrieval with either a single-lumen needle (SLN;N=22) or a double-lumen needle (DLN;N=22) to compare recovery rates and the technical aspects of their use. Two hundred ten and two hundred two follicles were aspirated with each needle, respectively. Follicular diameters were measured ultrasonically at the time of aspiration and recorded. One or more washes were performed when using the DLN and the SLN was withdrawn each time to recover the fluid in the dead space of the needle. The distribution of follicular sizes was the same for both needles. Oocyte recovery rates (SLN=65.7%; DLN=63.9%) and the incidence of fractured zonae (SLN=9.1%; DLN=6.4%) were the same for both needles (α>0.50; β<0.01). Although there were no differences between the two needles in the number of oocytes provided for IVF, there were technical differences. The DLN needle was more flexible and frequently deviated from the projected path as observed by ultrasound. The SLN may be preferable because it is technically easier to use; however, there may remain specific indications for the use of the DLN.

Estradiol and progesterone replacement regimens for the induction of endometrial receptivity

Initiation of pregnancy in premature ovarian failure patients by use of donated oocytes fertilized in vitro requires establishment of a normal endometrial environment. We compared administration of estradiol (E2) and progesterone (P) by polysiloxane vaginal rings versus oral micronized E2 and P vaginal suppositories in 10 such patients. Serum E2 levels were similar between groups and similar to normally-cycling controls. With vaginal administration of E2, a burst effect was noted, with marked elevation 1 hour after insertion. The pattern with oral administration was more consistent, although marked conversion to estrone occurred. The P cylinder and suppositories delivered similar levels, with diminution of P in some patients with the cylinder. Despite apparent limitations, endometrial histology was normal after each cycle; both groups achieved pregnancies. Administration of E2 and P by polysiloxane vaginal rings achieved hormonal levels similar to oral micronized E2 and P vaginal suppositories. Endometrial biopsies after the stimulated cycle were appropriately mature.

Timing of oocyte retrieval in cycles with a spontaneous luteinizing hormone surge in a large in vitro fertilization program

Forty-four cycles with a spontaneous luteinizing hormone (LH) surge among 377 in vitro fertilization (IVF) patients were studied for outcome with different timing of oocyte retrieval. Mean number of preovulatory oocytes per retrieval and per transfer was significantly less in these cycles than in controls. Mean number of preovulatory oocytes per retrieval and per transfer was significantly higher when the human chorionic gonadotropin (hCG)-retrieval interval was greater than 35 hours, compared with less than 24 hours. In cycles with an hCG-retrieval interval of less than 24 hours, percentage of preovulatory oocytes was higher when serum estradiol (E2) decreased by greater than 15% on the morning after hCG administration compared with a plateau or an increase in serum E2. Timing oocyte retrieval after spontaneous LH surge should consider the hCG-retrieval interval and changes in E2 levels after hCG administration; this may avoid cancellation for many patients.

Comparison between laparoscopically and ultrasonographically guided transvaginal follicular aspiration methods in an in vitro fertilization program in the same patients using the same stimulation protocol

SummaryOocyte recovery from 43 patients undergoing ultrasound-guided transvaginal oocyte retrieval was compared to a previous laparoscopic oocyte retrieval cycle from the same patient. Gonadotropin stimulation in both cycles was performed using the same protocol. There were no statistically significant differences in the mean day of oocyte retrieval or the mean daily estradiol level up to the day of oocyte retrieval between laparoscopic and transvaginal cycles. The total number of follicles aspirated per cycle, preovulatory oocytes aspirated per cycle, and number of concepti of preovulatory origin transferred per cycle were not statistically different. The number of immatue oocytes aspirated per cycle was statistically decreased in transvaginal retrieval cycles, which resulted in an increased total number of concepti transferred per transfer in laparascopic retrieval cycles. Twelve pregnancies resulted from the transvaginal retrieval cycles (27.9%), seven of which are ongoing or delivered. Ultrasound-guided transvaginal follicular aspiration yields results comparable to laparascopic retrieval in the same patients and should be the method of choice for oocyte pickup because of its many advantages.