Evaluation of the couple with infertility in a managed care environment.

The classic infertility evaluation is a costly experience for many couples. In the new era of managed care, it may be possible to perform a targeted evaluation that, while significantly lowering the total cost, will not impair our ability to correctly diagnose the cause of a couple's infertility. When combined with algorithms for streamlined treatment, it may be possible to significantly reduce the cost for the diagnosis and treatment of infertility.

Success rate with repeated cycles of in vitro fertilization-embryo transfer.

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.

Ovulation induction in the ovulatory woman.

Controlled ovarian hyperstimulation is frequently employed as empiric therapy for the treatment of unexplained infertility, mild male factor, cervical factor, and treated endometriosis. Prescribed in the form of either clomiphene citrate or gonadotropins, it is often combined with intrauterine insemination and offered to patients as a less expensive and less invasive alternative to the assisted reproductive technologies. Efficacy studies for these regimens are very important, as patients who would appear to be ideal candidates for this empiric therapy frequently do not suffer from absolute infertility; rather they are often subfertile, and may conceive spontaneously given enough time. Although there are few well-designed, controlled trials that assess the effectiveness of this form of therapy, the majority of the published data do suggest an improvement in pregnancy rates when compared to expectant management.

Elevated serum progesterone levels on the day of human chorionic gonadotropin administration in in vitro fertilization cycles do not adversely affect embryo quality.

OBJECTIVE: To assess the effect of an elevated serum P level on the day of hCG administration in an IVF cycle on resulting embryos by evaluating their performance at subsequent frozen ET. DESIGN: A retrospective study. PARTICIPANTS: Ninety-six consecutive patients undergoing frozen ET cycles were studied in a tertiary care center. MAIN OUTCOME MEASURES: Serum obtained on the day of hCG administration in an IVF cycle was assayed for E2 and P by RIA. The main outcome measured was the development of a clinical pregnancy in a subsequent frozen ET cycle. RESULTS: Using a previously described breakpoint in serum P concentration of 0.9 ng/mL (2.86 nmol/L), 8 of 69 (11.6%) frozen ETs in which embryos from low P level IVF cycles were transferred and 7 of 27 (25.9%) frozen ETs of embryos from elevated P level IVF cycles were transferred resulted in the development of clinical pregnancies. Although this does not clearly demonstrate superiority of embryos obtained from elevated P cycles, employing a power calculation, the probability that the pregnancy rate in the elevated serum P group is at least equal to the observed rate in the low P group is 92.8%. CONCLUSION: These data suggest that an elevated serum P level on the day of hCG administration does not adversely affect the quality of oocytes or resulting embryos.

Serum progesterone concentrations on the day after human chorionic gonadotropin administration and progesterone/oocyte ratios predict in vitro fertilization/embryo transfer outcome.

PURPOSE: In gonadotropin-releasing hormone analogue-pretreated in vitro fertilization-embryo transfer cycles, pregnancy rates are inversely related to serum progesterone levels on the day of administration of human chorionic gonadotropin. The relationship of the progesterone concentration on other days in the periovulatory period to pregnancy rates in such cycles is little studied. We therefore retrospectively analyzed the relationship between progesterone concentrations on the day after human chorionic gonadotropin and pregnancy in 114 cycles, 28 and 23 of which produced clinical and ongoing/delivered pregnancies, respectively. To assess the effect of the extent of follicular luteinization on success, we also studied the relationship between the progesterone concentration per oocyte retrieved and pregnancy for the day of and day after human chorionic gonadotropin. RESULTS: Progesterone concentrations on the day after human chorionic gonadotropin were inversely associated with clinical pregnancy by multiple logistic regression analysis (P < 0.05). Progesterone/oocyte ratios were inversely associated with clinical pregnancy (P < 0.05) and ongoing/delivered pregnancy (P < 0.02) for both the day of and the day after human chorionic gonadotropin. CONCLUSION: The study results extend the window of time during which elevated progesterone concentration is associated with poor outcome to at least 2 days. This finding is consistent with hypothetical mechanisms attributing the link between progesterone concentration and outcome to either endometrial or follicle/oocyte events. The association of lack of follicular luteinization (low progesterone per oocyte ratios) and favorable outcome suggests a predominant effect of progesterone on follicle/oocyte quality. Further studies are needed to clarify the mechanisms underlying the association between progesterone and in vitro fertilization-embryo transfer outcome.

Complications associated with the absorption of hysteroscopic fluid media.

OBJECTIVES: To review the literature concerning complications resulting from absorption of hysteroscopic fluid distension media and to describe methods to treat and prevent these complications. DESIGN: All pertinent literature on fluid distension media used for endoscopy, as well as relevant reports concerning the management of fluid and electrolyte imbalance, was reviewed. RESULTS: The absorption of large volumes of electrolyte-free, low-viscosity fluid may result in volume overload with water intoxication. Volume overload may cause pulmonary edema, and water intoxication may lead to hyponatremia, hypo-osmolarity, and cerebral edema. In contrast, the absorption of dextran-70 may cause volume overload secondary to the oncotic effect of intravascular dextran. Dextran-70 has been associated with anaphylaxis and coagulation disorders. TREATMENT: The use of diuretics is advocated. Urine output must be closely monitored. Judicious correction of electrolyte imbalance will prevent morbidity. PREVENTION: Meticulous attention to intraoperative fluid balance is imperative. A multichannel hysteroscope is necessary to keep intrauterine pressure low. Extensive surgical procedures may need to be performed in stages. CONCLUSIONS: Severe volume overload and electrolyte imbalance may result from fluid absorption during operative hysteroscopy. Most complications may be avoided by closely monitoring fluid balance intraoperatively.

Consecutive versus alternating cycles of ovarian stimulation using human menopausal gonadotrophin.

Ovarian stimulation is an effective treatment for patients with ovulatory dysfunction and unexplained infertility. An initial report has suggested that consecutive cycles of ovarian stimulation can be employed without causing a diminished response in the second cycle. However, this observation has neither been confirmed nor has a regimen of consecutive stimulation cycles been compared to one of alternating stimulation cycles. Accordingly, 44 consecutive and 54 alternating cycles of stimulation were evaluated in patients (n = 42) who were treated with human menopausal gonadotrophin (HMG) alone. Human chorionic gonadotrophin (HCG) 10,000 IU was administered i.m. when at least one follicle exceeded 16 mm in mean diameter, and this was followed by either intercourse or intrauterine insemination. Using each patient as her own control, we were unable to demonstrate any differences in mean HMG dose requirements, endocrine parameters or follicular development on the day of HCG administration, or ovulation rates in the second consecutive cycle compared to the second alternating cycle. Clinical pregnancies resulted significantly more often in a consecutive cycle (8/22) than in an alternating cycle (2/27, P = 0.029). We conclude that consecutive cycles of ovarian stimulation with HMG are not detrimental and may, in fact, result in increased cycle fecundity compared to alternating stimulation cycles.

A prospective, randomized trial comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles.

OBJECTIVE: To compare a single periovulatory intrauterine insemination (IUI) with a regimen employing two IUIs, one before ovulation and one after ovulation, in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) combined with human chorionic gonadotropin (hCG). DESIGN: A randomized, prospective trial. PARTICIPANTS: Thirty-one consecutive patients undergoing 49 cycles of controlled ovarian hyperstimulation/IUI were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Ovulation was determined sonographically. The establishment of a clinical pregnancy was defined by either ultrasonographic verification of cardiac activity within an intrauterine fetus, or histologic confirmation of trophoblast in a surgical specimen. RESULTS: Clinical pregnancies developed in 2 of 23 cycles in the single insemination group, compared with 12 of the 23 cycles in the double insemination group. Cycle fecundity was significantly higher for group II (0.522) than for group I (0.087) patients (P = 0.003). CONCLUSION: In hMG/hCG cycles, two IUIs timed as described above are superior to one periovulatory insemination.

Serum progesterone levels predict success of in vitro fertilization/embryo transfer in patients stimulated with leuprolide acetate and human menopausal gonadotropins.

Serum progesterone (P4) levels greater than 2.86 nmol/L (0.9 ng/mL) on the day of hCG administration are reportedly associated with decreased pregnancy rates in in vitro fertilization/embryo transfer (IVF/ET) cycles. To further assess this phenomenon we measured serial serum P4, LH, and estradiol levels in 115 consecutive patients undergoing stimulation for IVF/ET with midluteal leuprolide acetate and human menopausal gonadotropins. IVF/ET cycle outcome was retrospectively correlated with P4 levels on the day of hCG administration. Two critical breakpoints were identified, 1.27 nmol/L (0.4 ng/mL) and 286 nmol/L (0.9 ng/mL). Clinical pregnancies occurred in 9 of 18 patients in group I (P4, less than 1.27 nmol/L) compared to 11 of 81 patients in group II (1.27 less than P4 less than 2.86 nmol/L; P = 0.001) and 0 of 14 patients in group III (P4, less than or equal to 2.86 nmol/L) (P = 0.001). Eleven patients in group III had cryopreservation of embryos during that cycle. Six subsequently underwent frozen embryo transfer, and clinical pregnancies occurred in 2, both of whom have delivered. These findings demonstrate that even modest increases in serum P4 levels (greater than 1.27 nmol/L) are associated with reduced pregnancy rates in IVF/ET cycles. In addition, it appears that the mechanism may not exclusively involve poor oocyte quality.

Follicular size at the time of human chorionic gonadotropin administration predicts ovulation outcome in human menopausal gonadotropin-stimulated cycles.

OBJECTIVE: The objectives of this study were: (1) to correlate follicle size by transvaginal sonography with ovulation outcome in cycles of controlled ovarian hyperstimulation with human menopausal gonadotropins; (2) to determine if follicular size on the day of human chorionic gonadotropin (hCG) administration predicts the incidence of ovulation; and, if so, (3) to derive a mathematical model that predicts the number of expected ovulations in any given cycle of controlled ovarian hyperstimulation. DESIGN: A retrospective analysis. PARTICIPANTS: Forty-nine consecutive patients undergoing 122 cycles of controlled ovarian hyperstimulation were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Follicular size and evidence of ovulation were determined sonographically. The main outcome measure was the rate of ovulation per follicle size. RESULTS: The percentages of follicles measuring less than or equal to 14 mm, 15 to 16 mm, 17 to 18 mm, 19 to 20 mm, and greater than 20 mm on the day of hCG administration that subsequently ovulated were 0.5%, 37.4%, 72.5%, 81.2%, and 95.5%, respectively. CONCLUSIONS: (1) Follicular size on the day of hCG administration correlates with the incidence of ovulation. (2) The expected number of ovulations in any given controlled ovarian hyperstimulation cycle can be predicted with 95% confidence using the accompanying equation.

Reproductive surgery vs assisted reproductive technologies: selecting the correct alternative.

Many innovations have been made in advanced reproductive technologies (ART) over the past several years. These procedures now yield pregnancy rates of over 20% per cycle, rates that compare favorably to many types of reproductive surgery. Therefore, ART now represents a viable alternative for many patients suffering from infertility. As these pregnancy rates continue to rise, gynecologists will have to choose between ART and reproductive surgery for a larger number of patients. This article reviews the commonly performed reproductive surgical procedures and compares expected postoperative pregnancy rates to those of ART in order to help the gynecologist make this decision.

Establishment of TEST-yolk buffer enhanced sperm penetration assay limits for fertile males.

TEST-yolk buffer has been shown to enhance sperm penetration of zona-free hamster eggs. Review of sperm penetration assay (SPA) data from a fertile population was undertaken to determine a normal range for SPA with TEST-yolk buffer enhancement. Thirty-eight intrauterine insemination patients and 4 artificial insemination donors who had successfully initiated a pregnancy within 18 months of SPA analysis were examined. All 42 enhanced SPAs demonstrated penetration of greater than 10%, and 37 of these (88%) yielded SPA values of greater than or equal to 20%. Thirty-three percent (14/42) of these individuals achieved 0% penetration in the SPA without TEST-yolk buffer. The SPA performed with the TEST-yolk modification has fewer false negatives than the assay done with the original methodology.

Ovarian cyst aspiration prior to initiating ovarian hyperstimulation for in vitro fertilization.

Twenty-three consecutive patients presenting for in vitro fertilization were evaluated with transvaginal sonography on cycle day 3, prior to initiating ovarian hyperstimulation. Three of these patients were noted to have large ovarian cysts. All three underwent transvaginal aspiration of the cysts, followed immediately by initiation of ovarian hyperstimulation. Following oocyte retrieval, in vitro fertilization, and embryo transfer, all three women achieved pregnancy. We conclude that cyst aspiration is not contraindicated when an ovarian cyst is encountered in the follicular phase of an in vitro fertilization cycle.