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.     

Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer

OBJECTIVE: To determine if an increase in plasma P occurring before hCG administration might impair the outcome of IVF-ET. DESIGN: Five hundred eighty-five IVF-ET cycles were prospectively studied for the occurrence of plasma P elevation before hCG administration. SETTING: Tertiary institution, IVF-ET program, H?pital A. Béclère. PATIENTS: Participating patients included IVF-ET candidates 23 to 42 years of age only, excluding the couples in whom a male factor was a primary or an accessory cause of infertility. MAIN OUTCOME MEASURES: To clarify the practical consequences on IVF-ET outcome of pre-hCG increases in plasma P, we studied 585 consecutive IVF-ET cycles. These were divided into two groups according to plasma P levels observed on the day of hCG administration; plasma P of 0.9 ng/mL (2.9 nmol/L) was taken as an arbitrary cutoff value. Group A included 485 IVF cycles in which plasma P was < or = 0.9 ng/mL (2.9 nmol/L); group B included the remaining 100 cycles in which plasma P was > 0.9 ng/mL (2.9 nmol/L). RESULTS: The number of mature oocytes retrieved, the oocyte cleavage rate, and the number of embryos obtained were similar in groups A and B. In contrast to this apparent similarity in oocyte quality, a decrease in pregnancy rate (PR) and a trend for a decrease in embryo implantation rate were observed in group B in comparison with group A. CONCLUSIONS: The similar fertilization and cleavage rates obtained in groups A and B suggest that pre-hCG elevation in plasma P does not lead to decreased oocyte quality. Yet the lower PR observed when plasma P rises prematurely suggests that the prolonged but discrete elevation in plasma P occurring in these cases might alter endometrium receptivity to embryo implantation.     

Premature progesterone elevation spares blastulation but not pregnancy rates in in vitro fertilization with coculture

OBJECTIVE: To clarify whether embryo development to the blastocyst stage may be affected by premature P elevation during controlled ovarian hyperstimulation (COH) for IVF-ET with embryo coculture. DESIGN: Retrospective study. SETTING: Tertiary care infertility center. PATIENT(S): One hundred thirty-one women undergoing 153 IVF-ET cycles with embryo coculture. INTERVENTION(S): Patients underwent COH with GnRH agonist and hMG. Embryos were cocultured up to the blastocyst stage. According to plasma P levels on the day of hCG, two groups were defined: low P (P < or = 0.9 ng/mL; conversion factor to SI unit, 3.180) and high P (P > 0.9 ng/mL). MAIN OUTCOME MEASURE(S): Blastulation (number of blastocysts/number of noncavitating embryos x 100) and pregnancy rates (PRs). RESULT(S): Blastulation rates were similar in the low and high P groups (51% and 48%, respectively). Moreover, patients included in the high P groups achieved significantly lower clinical and ongoing PRs (12% versus 29% and 7% versus 25%, respectively). CONCLUSION(S): The lack of difference in blastulation rates between the groups further supports the hypothesis that premature P elevation does not alter oocyte and embryo quality. Hence, the observed decrease in PRs is likely to reflect impaired endometrial receptivity in the high P group.     

Physiopathology of premature progesterone elevation

OBJECTIVE: To determine the effects of the last hMG administration on plasma P and androgen profiles during controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN: Controlled clinical study. SETTING: The IVF-ET program of a tertiary outpatient care center, H?pital A. Béclère, Clamart, France. PATIENTS: Nine IVF-ET candidates aged 25 to 36 years having presented normal responses to COH in previous IVF-ET cycles. INTERVENTIONS: Controlled ovarian hyperstimulation was induced for IVF-ET using hMG after endogenous gonadotropins were suppressed with a time-release GnRH agonist. Just before the last hMG administration (225 IU), the participants were hospitalized for 24 hours for serial blood sampling. These occurred before (baseline) and after hMG administration, every 30 minutes for 1 hour, hourly for 4 hours, and every 3 hours for the remaining part of a 24-hour post-hMG observation period. MAIN OUTCOME MEASURE: Measurement of P, T, androstenedione (A), E2, FSH, and LH. RESULTS: Plasma P and androgens (T and A) increased significantly, reaching peak values 12 to 15 hours after hMG administration and decreased progressively thereafter, to reach values not significantly different from baseline 24 hours after hMG administration. Plasma E2 levels increased progressively and steadily during the 24-hour observation period. Plasma FSH levels remained constant after hMG administration while LH stayed undetectable. CONCLUSION: In COH cycles induced for IVF-ET, the hormonal profile after the last hMG injection suggests that hMG triggers an increase in plasma P and androgens that culminates 12 to 15 hours after hMG administration. This elevation in plasma P and androgens observed after hMG administration is likely to reflect a direct action of the LH and/or FSH components of hMG on granulosa cells. In some women these hormonal consequences of hMG treatment may impair endometrial receptivity in IVF-ET cycles.     

The dental management of patients with natural rubber latex allergy

PURPOSE: The use of highly purified follicle-stimulating hormone (Metrodin-HP) was compared with that of a preparation containing follicle-stimulating hormone and luteinizing hormone (Pergonal) for production of superovulation in an IVF program. METHODS: We used the Oxford Fertility Unit database to identify patients undergoing their first cycle of IVF, using either Metrodin-HP or Pergonal. Patients were treated with a standardized drug protocol and were stratified by age and cause of infertility. Ovarian stimulation with either Metrodin-HP (Serono Laboratories) or human menopausal gonadotropin (hMG; Pergonal; Serono Laboratories) after pituitary desensitization commenced in the midluteal phase of the preceding cycle. Monitoring was performed by ultrasound and serum estradiol measurement prior to transvaginal oocyte recovery, followed by IVF and transfer of no more than three embryos. RESULTS: For Metrodin-HP versus Pergonal, the rates of egg retrieval (98 vs 94%), fertilization (89 vs 92%), clinical pregnancy (32.9 vs 23.4%), miscarriage (4.1 vs 4.5%), live birth (26 vs 18.5%), and ovarian hyperstimulation syndrome (5.5% vs 5.9%) were similar in both groups. The apparent increase in clinical pregnancy and live birth with Metrodin-HP did not reach statistical significance. The dosages of gonadotropins used were comparable. Estradiol levels measured on day 8 of stimulation were significantly lower in the Metrodin-HP group than in the Pergonal group, but the difference did not reach statistical significance on the day of hCG administration. Significantly more follicles (greater than 12 mm) were obtained in the Metrodin-HP group, but the numbers of eggs recovered and fertilized were similar in the two groups. CONCLUSIONS: These findings demonstrate that highly purified FSH (Metrodin-HP) is as effective and successful as hMG (Pergonal) for ovarian stimulation in a standard IVF regimen. Exogenous luteinizing hormone (LH) is not required for satisfactory ovarian stimulation in IVF. Measurement of estradiol may be less helpful in the monitoring of Metrodin-HP cycles, but the level reached on the day of hCG administration can still be used to predict, and hence avoid, ovarian hyperstimulation syndrome.     

Ultrasonography as a primary diagnostic tool in patients with inflammatory disease and tumors of the small intestine and large bowel

PURPOSE: The administration of two GnRH analogues (buserelin and leuprolide acetate) in long and short protocols was evaluated prospectively. In the long protocol, the analogues were given from day 1 of the cycle for at least 14 days and then hMG administration was started, while in the short protocol the analogues were initiated from cycle day 1, adding hMG from day 3. The patients were divided into four groups according to the protocol used: Group I, buserelin-long; Group II, buserelin-short; Group III, leuprolide-long; and Group IV, leuprolide-short. Serum E2 levels on the day of hCG injection and the number of follicles observed, oocytes retrieved, and embryos obtained, as well as implantation rates, were significantly higher (P < 0.001) in the long protocols than in the short ones. RESULTS: Pregnancy rates were similar in all groups, although a trend for better results was observed in buserelin-long compared to buserelin-short. There were no differences in the results achieved with buserelin or leuprolide. CONCLUSION: The administration of GnRH analogues (buserelin and leuprolide acetate) in long protocols induced a more intense ovarian response and was associated with significantly higher implantation rates and also a trend for higher pregnancy rates, although this difference was not statistically significant.     

Controlled hyperstimulation in intra-uterine inseminations: hMG-hCG protocol (204 cycles)

OBJECTIVE: to evaluate the results of superovulation, protocol hMG-hCG, associated to IUI for treatment of infertility. PATIENTS AND METHODS: this prospective study, includes 77 couples who underwent 204 consecutive cycles of homologous IUI. The same protocol was applied for all the couples. hMG was administrated from cycle days 2 to 5 (3 then 2 ampuls per day). Patients were monitored daily, by evaluation of serum oestradiol. Insemination was done 36 to 38 hours after hCG injection. RESULTS: 2.6 cycles were done per couple. We observed 16.2% pregnancy per cycle. The best results were obtained in female indications, in the first cycle, with more than 500,000 spermatozoide and with a level of E2 between 500 and 1500 pg/ml. Multiple pregnancy was observed in 18.2%. CONCLUSION: controlled ovarian stimulation should be associated to all IUI.     

Young low responders protected from untoward effects of reduced ovarian response

OBJECTIVE(S): To correlate fertilization and clinical pregnancy rates (PRs) in low responders with their E2 levels (<500, 500-800, >800-1,000 pg/mL), age (20-30, 31-40, >40 years), number of follicles, and number of oocytes retrieved. DESIGN: A retrospective study. SETTING: The IVF unit of an academic hospital. PATIENT(S): One hundred forty-three women who failed to attain E2 levels of 1,000 pg/mL on the day of hCG administration. INTERVENTION(S): Controlled ovarian hyperstimulation, blood E2 and progesterone measurements, ultrasonographic scanning of ovarian follicles, oocyte retrieval after hCG administration, and ET. MAIN OUTCOME MEASURE: Clinical PR. RESULT(S): Although E2 levels, fertilization rates, age, and number of oocytes did not differ significantly between the three age groups, the PR achieved in the youngest group was approximately three times as high (19.3%) as that achieved in the two older groups. CONCLUSION: Young low responders represent a unique subset in that their age protects them from the deleterious effects of poor ovarian response.     

Important microsatellite markers in the investigation of replication errors (RER) in colorectal carcinomas

PURPOSE: Our purpose was to assess the value of monitoring serum P and inhibin A to determine how values might improve the clinical monitoring of natural cycle in vitro fertilization (IVF)-embryo transfer (ET) patients. METHODS: All patients (n = 26) who underwent natural-cycle IVF-ET (n = 35) were analyzed. Groups were evaluated according to patients who had a spontaneous luteinizing hormone (LH) surge (group I) and women receiving human chorionic gonadotropin (hCG) who underwent subsequent oocyte aspiration (group II). Group II was further evaluated according to women who did (n = 10) and did not (n = 7) have an ET. All cycles were evaluated with serial transvaginal ultrasonography and serum estradiol, progesterone, and inhibin A. When follicle maturity was achieved, hCG, 10,000 IU, was administered intramuscularly if a LH surge was not detected. Transvaginal ultrasound-guided aspiration was performed 34-36 hr after hCG administration followed by a 48-hr transcervical ET. RESULTS: No differences were seen in cycles the day prior to (d-1) and the day of a spontaneous LH surge, (n = 18) or hCG (d-0)(n = 17) in group I or group II with respect to lead follicular diameter (d-1, 15.3 +/- 0.6 vs. 14.2 +/- 0.9 mm; d-0, 17.4 +/- 0.8 vs. 17.8 +/- 0.6 mm) and serum estradiol (d-1, 148 +/- 15 vs. 150 +/- 15 pg/ml; d-0, 218 +/- 15 vs. 199 +/- 16 pg/ml), respectively. However, serum progesterone was significantly elevated in group I compared with group II on d-1 (0.82 +/- 0.6 vs. 0.48 +/- 0.04 ng/ml; P < 0.05) and d-0 (1.1 +/- 0.12 vs. 0.63 +/- 0.08 ng/ml; P < 0.05). Inhibin A was significantly greater on d-1 in group I (24 +/- 2.5 vs. 15 +/- 2.2 pg/ml; P < 0.05). In group II, cycles that resulted in an ET (n = 10) compared with group II cycles that did not (n = 7) revealed a significant difference in serum progesterone (0.51 +/- 0.05 vs. 0.7 +/- 0.07 ng/ml; P < 0.05) and inhibin A (15 +/- 2.5 vs. 37.3 +/- 5 pg/ml; P < 0.05) the day of hCG. CONCLUSIONS: The possible application of serum progesterone and inhibin A in managing natural-cycle IVF-ET is suggested. These assays may predict women who should be set up for egg retrieval, while cancelling others in spite of the absence of an LH surge.     

Computerized assessment of endometrial echogenicity: clues to the endometrial effects of premature progesterone elevation

OBJECTIVE: To determine whether premature progesterone elevation affects the timing of hyperechogenic transformation of the endometrium during the early luteal phase of controlled ovarian hyperstimulation (COH) cycles. DESIGN: Prospective analysis. SETTING: Assisted Reproduction Unit, H?pital Antoine Béclère, Clamart, France. PATIENT(S): Fifty-nine women undergoing 59 IVF-ET cycles. INTERVENTION(S): Patients underwent COH with a GnRH agonist and hMG. Endometrial echogenicity was assessed on the days of hCG administration, oocyte retrieval, and ET. Results are expressed as the extent of submyometrial hyperechogenic area in relation to the total endometrial surface as determined by a computer-assisted analysis system. Patients were sorted according to whether their plasma progesterone level exceeded 0.9 ng/mL (n = 26) or not (n = 33) on the day of hCG administration. MAIN OUTCOME MEASURE(S): Endometrial echogenicity. RESULT(S): On the day of hCG administration, the degree of endometrial echogenicity was similar in both groups (41% vs. 40%), but after hCG administration, it increased significantly faster in the high progesterone group than in the low progesterone group (70% vs. 63% at oocyte retrieval and 90% vs. 79% at ET, respectively). CONCLUSION(S): End-follicular phase elevation in plasma progesterone (>0.9 ng/mL on the day of hCG administration) was associated with a faster increase in endometrial echogenicity during the early luteal phase of COH cycles. This observation is consistent with the hypothesis that premature progesterone elevation hastens the secretory transformation of the endometrium.     

Prospective randomized trial of the effect of two flushing media on oocyte collection and fertilization rates after in vitro fertilization

OBJECTIVE: To assess the value of heparinized saline as a flushing medium for oocyte recovery. DESIGN: Prospective randomized study. SETTING: Academic tertiary referral center for fertility treatment. PATIENT(S): Thirty-five patients, with both ovaries intact having IVF-ET. INTERVENTION(S): Patients were randomized either to have the follicles of the left or right ovary flushed with heparinized normal saline at the time of oocyte recovery for IVF-ET. The contralateral ovary was flushed with heparinized culture medium. Oocytes obtained from each side were cultured separately and assessed for fertilization 18-21 hours after insemination. MAIN OUTCOME MEASURE(S): Collection and fertilization rates. RESULT(S): A total of 481 follicles were aspirated yielding 366 oocytes. Of these, 240 fertilized. From the side flushed with saline 185 oocytes were collected from 237 follicles, which was not significantly different from 181 oocytes collected from 244 follicles on the side flushed with culture medium (odds ratio = 1.23; 95% confidence interval = 0.79-1.92). Similarly, there was no significant difference observed in fertilization rates between oocytes obtained after saline (median 71.4%) and culture medium flush (median 75.0%) (odds ratio = 1.08; 95% confidence interval = 0.68-1.72). CONCLUSION(S): Heparinized normal saline is an equally good but cheaper and more convenient medium than standard heparinized culture medium and could replace it for flushing follicles during oocyte recovery for IVF-ET procedures.     

Human follicular fluid proteoglycans in relation to in vitro fertilization

OBJECTIVE: To determine whether the concentrations of proteoglycans and hyaluronan in human follicular fluid (FF) are associated with follicular volume, oocyte fertilization, and ET during IVF. DESIGN: The FF from individual follicles were collected. Enzyme-linked immunosorbent assay methods for quantification of a larger chondroitin sulfate proteoglycan and a smaller composite heparan-chondroitin sulfate proteoglycan were established. Hyaluronan and E2 were measured by RIA techniques. PATIENT(S): Sixteen infertile women participating in the IVF program. MAIN OUTCOME MEASURE(S): Concentrations of the proteoglycans, follicular volume, fertilization, and ET rates. RESULT(S): The follicles contained high concentrations of proteoglycans with an average of 0.8 mg/mL of FF, and approximately 70% consisted of the larger chondroitin sulfate proteoglycan, and 30% of the heparan-chondroitin sulfate proteoglycan. A negative correlation was found between the follicular volume, the chondroitin sulfate proteoglycan (r = -0.43), and hyaluronan (r = -0.56). The percentage of embryos developed in culture was significantly higher in follicles larger than 2 mL. A significant and 35% lower concentration of the chondroitin sulfate proteoglycan was found in larger follicles from which subsequent ET was observed. THe heparan-chondroitin sulfate proteoglycan and hyaluronan were both unrelated to fertilization and ET in vitro. CONCLUSION(S): Lower concentrations of chondroitin sulfate proteoglycan were associated with higher follicular volumes and greater fertilization and ET rates. These associations could merely reflect the maturation of the follicle or a role of the chondroitin sulfate proteoglycan in the fertilization process.     

The results of an in vitro fertilization program: two regimens of superovulation

Gonadotropin-releasing hormone (GnRH) agonists are increasingly used in ovarian hyperstimulation protocols in in vitro fertilization (IVF) programs. From March 1992 to June 1993, 565 patients attending our Institute underwent superovulation in 1104 IVF program cycles. Of these cycles, 650 were stimulated with clomiphene citrate and gonadotropins (human menopausal gonadotropin/hMG), and 454 with the GnRH agonist buserelin and hMG in a group of patients who had earlier failed to respond or did not conceive after clomiphene citrate/hMG stimulation. The ovarian response was similar in both groups, however, with the use of buserelin more oocytes were recovered -4.9 +/- 3.2 and 3.5 +/- 2.3 oocytes, respectively. The clinical pregnancy rate per transfer in the group of patients superovulated with buserelin/hMG was twice that of the clomiphene citrate/hMG group (21.0% vs. 10.4%). The relatively high pregnancy rate with the buserelin/hMG regimen in the group of 'poor responders' may be connected with GnRH agonist-induced pharmacological hypophysectomy and the sequelae thereof: normalization of some endocrinopathies, absence of an endogenous luteinizing hormone (LH) surge and better endometrium receptivity, oocytes and embryo quality.     

Human menopausal gonadotropin during in vitro maturation of human oocytes retrieved from small follicles enhances in vitro fertilization and cleavage rates

OBJECTIVES: To compare the IVF rates of oocytes retrieved from small follicles (< 2 mL in volume) with those of oocytes retrieved from large follicles and to test the effect of adding gonadotropins to the IVF medium on the fertilization rates of oocytes from small follicles. DESIGN: Oocytes were retrieved with endovaginal ultrasound (US) guidance from patients undergoing infertility treatment in our IVF program. Oocytes were grouped according to the volume of the originating follicle and subjected to our routine procedure for IVF. HMG was added to the IVF medium for some of the oocytes from small follicles. SETTING: Toronto Fertility and Sterility Institute is affiliated with the University of Western Ontario and University of Toronto and is equipped for RIA, endovaginal US monitoring and oocyte retrieval, and for processing and culturing gametes and embryos. PATIENTS: Infertile patients admitted to our IVF program. INTERVENTIONS: Patients underwent ovarian stimulation with hMG before oocyte retrieval. No other interventions were introduced to the processing and culturing the gametes and embryos except the addition of hMG to the medium of some of the small follicle-originated oocytes with the informed consent from the patients. MAIN OUTCOME MEASURES: Rates of fertilization, cleavage of the fertilized embryos before replacement, and meiotic status of some of the oocytes from small follicles. RESULTS: Most of the oocytes from small follicles did not complete the first meiotic division; they had low rates of fertilization and cleavage compared with oocytes from large follicles, and these rates were improved by the addition of hMG to the IVF medium. CONCLUSIONS: Oocytes from small follicles are probably less mature and require a more physiological environment to achieve normal rates of fertilization and cleavage.     

Human chorionic gonadotrophin and steroid concentrations in follicular fluid: the relationship to oocyte maturity and fertilization rates in stimulated and natural in-vitro fertilization cycles

The study investigates the relationship of follicular fluid steroids and human chorionic gonadotrophin to oocyte maturity and fertilization rates in stimulated and natural cycles. Oestradiol, progesterone, testosterone and human chorionic gonadotrophin were quantified in 129 samples of follicular fluid and the progesterone:oestradiol ratio calculated. Both stimulated cycles (short and long luteinizing hormone-releasing hormone/human menopausal gonadotrophin regimens) and natural cycles were compared. A total of 60 women were studied, 20 in each group. In the natural cycles, testosterone was significantly lower in follicles with intermediate oocytes (P = 0.015). Both oestradiol and testosterone were significantly lower in stimulated cycles compared to natural cycles (P = 0.032 and P = 0.034 respectively). In the ovarian stimulation cycles, the progesterone:oestradiol ratio was significantly higher when oocytes fertilized (P = 0.052). Moreover, in the stimulated cycles, oestradiol and human chorionic gonadotrophin were singnificantly lower in the short protocol compared to the long protocol. The data demonstrate that the hormonal milieu of the follicle is altered in down-regulated stimulated cycles to varying degrees, depending partially on the type of protocol used. Furthermore, the progesterone:oestradiol ratio, rather than individual hormone concentrations, may be a useful predictor of the fertilizing capacity of the oocytes.     

Relationship between urinary estrone conjugates as measured by enzyme immunoassay and serum estradiol in women receiving gonadotropins for in vitro fertilization

OBJECTIVE: Our purpose was to determine whether urinary estrone conjugates (E1C) as measured by enzyme immunoassay correlate with serum estradiol (E2) in women undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins. DESIGN: This was a prospective, clinical study. SETTING: The study took place in an outpatient, university-affiliated in vitro fertilization (IVF) unit. INTERVENTIONS: First morning urine samples were analyzed for E1C using a competitive solid-phase microtiter enzyme immunoassay and the value was corrected for urinary creatinine (E1C/Cr). The value was compared to morning serum E2 as determined by radioimmunoassay. RESULTS: Mean E2 and E1C/Cr levels demonstrated a similar pattern on the days before hCG administration. The correlation between E1C and E2 was 0.85 (P < 0.0001). Furthermore, the correlation between the number of follicles greater than 12 mm was as high for E1C/Cr (rho = 0.71, P < 0.001) as it was for E2 (rho = 0.74, P < 0.0001). CONCLUSIONS: Urinary E1C/Cr levels in women receiving hMG correlate with serum E2. Further studies are necessary to determine whether E1C is clinically useful to predict ovarian hyperstimulation syndrome.     

Non-constrained elbow arthroplasty for mutilans deformity in rheumatoid arthritis: a report of six cases

OBJECTIVE: To analyze the effect on uterine receptivity of a decrease in E2 levels during the preimplantation period with the use of a step-down regimen in high responders undergoing IVF. DESIGN: Prospective controlled clinical study. SETTING: The Instituto Valenciano de Infertilidad. PATIENT(S): High responders in whom at least one previous IVF attempt failed in which 3-4 good-quality embryos were transferred and E2 levels were >3,000 pg/mL on the day of hCG administration. INTERVENTION(S): Gonadotropins were administered according to two different protocols. Blood samples were collected and IVF was performed. MAIN OUTCOME MEASURE(S): Serum E2 levels and reproductive outcome of IVF. RESULT(S): Estradiol levels on the day of hCG administration and throughout the preimplantation period and the number of oocytes collected were significantly lower with the use of the step-down regimen than during the previous failed cycle in which the standard protocol was used. The fertilization rate was similar and the number of good-quality embryos transferred was comparable. However, the implantation and pregnancy rates were significantly improved in patients who underwent the step-down regimen compared with those who received the standard protocol. CONCLUSION(S): With the use of a step-down regimen with FSH in high responders, our clinical results demonstrate that uterine receptivity can be improved when E2 levels are decreased during the preimplantation period.     

Elevated antitoxin titers in a man with generalized tetanus

STUDY OBJECTIVE: To compare the outcome of in vitro fertilization and embryo transfer (IVF-ET) after laparoscopic surgery in women with endometriosis with that of patients with tubal factor infertility. DESIGN: Retrospective survey of hospital and office charts using a computerized worksheet. SETTING: Lin-Kou medical center of Chang Gung Memorial Hospital. PATIENTS: Sixty-seven women with minimal to mild or moderate to severe endometriosis. Women with tubal factor infertility without other associated disorders (60 cycles) made up the control group. INTERVENTIONS: Seventy-five consecutive cycles of IVF-ET were performed in these patients who failed to conceive after laparoscopic conservative surgery. MEASUREMENTS AND MAIN RESULTS: The concentration of serum estradiol on the day of human chorionic gonadotropin (hCG) injection, the day of hCG injection, clinical pregnancy rates per transfer, number of follicles larger than 14 mm, number of embryos transferred, and implantation rate were not significantly different between women with endometriosis and those with tubal factor infertility. The number of oocytes retrieved and number fertilized were decreased, and the basal level of follicle-stimulating hormone on cycle day 3 was higher in women with both degrees of endometriosis. Women in both endometriosis groups received more follicle-stimulating hormone and human menopausal gonadotropin than those with tubal factor infertility. CONCLUSIONS: The outcome of IVF-ET in patients with endometriosis after laparoscopic surgery did not differ from that in the group with tubal factor infertility, but the former required more ampules of gonadotropin to achieve the same response. The advantages of laparoscopic surgery in women with endometriosis should be probably correlated with success of IVF-ET.     

Withholding gonadotropin administration is an effective alternative for the prevention of ovarian hyperstimulation syndrome

OBJECTIVE: To evaluate the outcomes of IVF and the incidence of ovarian hyperstimulation syndrome (OHSS) after discontinuing gonadotropin therapy in patients at risk of developing OHSS by delaying hCG administration until a drop in serum E2 levels was observed. DESIGN: Retrospective study. SETTING: IVF program at a university center. INTERVENTIONS: Gonadotropin administration was withheld in 22 patients (group 1) when their serum E2 level was > or = 3,000 pg/mL (conversion factor to SI unit, 3.671). Patients continued GnRH analogue injections daily, and hCG was administered when serum E2 levels dropped to < or = 3,000 pg/mL. Outcomes were compared with 26 patients (group 2) in whom embryo transfer was canceled and all embryos cryopreserved for transfer during a subsequent unstimulated cycle. MAIN OUTCOME MEASURES: Outcomes of IVF and incidence of OHSS were compared in both groups of patients. In group 1, follicular and hormonal parameters before and after the coasting interval were compared in pregnant versus nonpregnant patients. In addition, serum hormonal profiles were evaluated daily during the coasting period to determine the effects of gonadotropin withdrawal. RESULTS: Although the mean number of oocytes retrieved was significantly higher in group 2, fertilization rates, miscarriage rates, delivery rates/stimulation cycle, and the incidence of OHSS did not differ significantly between the two groups. CONCLUSION: Withholding gonadotropin administration is an effective alternative to prevent the development of severe OHSS in a high-risk population. Although the risk of cancellation cannot be completely eliminated, this strategy can provide a high pregnancy rate without the need to repeat multiple frozen-thawed cycles.     

Prostaglandin synthesis by cumulus-oocyte complexes: effects on in vitro fertilization in mice

Cumulus-oocyte complexes, obtained from superovulated Balb/C virgin female mice, released to the incubation media significant amounts of PGE1, PGE2 and PGF2 alpha, as estimated by bioassay. Fertilization rates in vitro decreased sharply when cumulus-oocyte complexes were treated with indomethacin (10(-6) M) and then inseminated with 5000 sperm per oocyte. In order to explore if the reduced prostaglandin (PG) concentration was responsible for diminished fertilization rates, PGE1, PGE2 and PGF2 alpha (10(-9) M) were added to the fertilization media of treated oocytes. PGE1 and PGE2 but not PGF2 alpha returned fertilization rates to control levels. Besides, PGE1 (10(-9) M) enhanced fertilization rates with reduced sperm numbers (1000 sperm per oocyte) of untreated cumulus-oocyte complexes. In conclusion, PG synthesis and release of mouse cumulus-oocyte complexes affects fertilization in vitro, and it is suggested that PGs of the E series modulate sperm function at the moment of fertilization.