Ultrasound is the optimal choice for guidance in difficult hysteroscopy.

OBJECTIVES: To compare costs and complications associated with ultrasound-guided hysteroscopy vs laparoscopy-guided hysteroscopy vs hysteroscopy alone for the surgical repair of intrauterine septa and synechiae. METHODS: This was a retrospective cohort study. Charts of all patients undergoing reparative surgery for intrauterine synechiae or uterine septa at our academic institution between 2000 and 2008 were reviewed. A total of 159 procedures were included in the study, categorized into concurrent laparoscopic guidance (n = 69), ultrasound guidance (n = 52) or no guidance (n = 38). Data regarding billing, surgical case logs and complications were collected for these procedures. Using these data, complication rates and inflation-adjusted charges were compared between the groups. Statistical analysis was performed using Fisher's exact test and Student's t-test, as appropriate. RESULTS: A uterine perforation rate of 8.7% was observed with laparoscopic guidance vs 1.9% with ultrasound guidance (P = 0.12) and 5.3% with no guidance (P = 0.41). Analysis of billing data showed that average total costs were significantly less for ultrasound guidance than for laparoscopic guidance ($9124 vs $11 895, P < 0.001). Ultrasound guidance did not increase costs over hysteroscopy alone ($9124 vs $8242, P = 0.54). CONCLUSION: Real-time transabdominal ultrasound guidance during the resection of intrauterine synechiae or septa resulted in a trend towards reduced uterine perforation. Moreover, ultrasound guidance is less costly than laparoscopic guidance and adds no additional cost over hysteroscopy alone. Taken together, transabdominal ultrasound guidance is the optimal means of intraoperative guidance for the resection of uterine synechiae and septa.

Peritoneal macrophages modulate human granulosa-luteal cell progesterone production.

Macrophages have been identified in the developing corpus luteum in several species, including man, and also constitute approximately 90% of cells in the peritoneal cavity. We studied the effect of peritoneal macrophages or blood monocytes on progesterone (P) synthesis by human granulosa cells from preovulatory follicles obtained at laparoscopy of 14 women undergoing in vitro fertilization. Pooled granulosa cells from follicles with mature ova were isolated by Ficoll-Hypaque gradient centrifugation. Washed granulosa cells (0.75 X 10(5)/ml) were incubated in Dulbecco's Minimum Essential Medium containing 20% calf serum with varying concentrations of pelvic macrophages (0.8-29 X 10(5)/ml) or fresh and mature blood monocytes (0.25-2.5 X 10(5)/ml). P production was determined by RIA of medium at 24-h intervals for 24-48 h. In situ concentrations of pelvic macrophages from 8 patients with tubal infertility increased cumulative P production to 140 +/- 17.8% (mean +/- SEM) of the control values. A similar increase (182 +/- 62.7%) was found with macrophages from 6 patients with endometriosis or unexplained infertility. Both fresh and mature monocytes stimulated P production to 225% and 261% of control values, respectively. Indomethacin (10(-4) M) or monoclonal antibody to somatomedin-C did not prevent stimulation of P production. These results suggest that peritoneal macrophages may exert luteotropic effects on cumulus cells while the ovulated oocyte resides in the tube, and incoming monocytes may be important in stimulating luteal cells in the developing corpus luteum.

Cyclic changes of peritoneal fluid parameters in normal and infertile patients.

This study compared peritoneal fluid volume, macrophage count, and macrophage concentration by diagnosis and cycle week of 426 patients undergoing laparoscopy. Patient diagnosis and cycle week had no significant interaction. Peritoneal fluid volume was dependent upon cycle week and diagnostic group, but macrophage count depended only upon diagnostic group. Endometriosis was associated with a significantly elevated total number of macrophages. Postovulatory peritoneal fluid volumes were significantly higher than preovulatory values. Cyclic and postovulatory differences in peritoneal fluid volume support proposed pathophysiologic roles.

Transvaginal sonographic detection of endometrial polyps with fluid contrast augmentation.

Injection of the endometrial cavity with isotonic solutions during transvaginal sonography was used to confirm the presence and location of endometrial polyps. Fourteen infertility patients, 13 of them asymptomatic, had polyps detected in this manner. Confirmation and treatment took place via hysteroscopy. Potential indications for this readily available and inexpensive technique vary from infertility to menometrorrhagia.

The effects of smoking on ovarian function and fertility during assisted reproduction cycles.

OBJECTIVE: To investigate the effects of cigarette smoking on ovarian function and fertility in women undergoing assisted reproduction cycles. METHODS: We assessed the effects of smoking on ovarian function and fertility in a cohort of 499 women. Questionnaires were designed to quantify past smoking exposure and to determine whether the woman was smoking during the treatment cycle. Ovarian function characteristics and pregnancy rates were compared among current smokers, past smokers, and nonsmokers. RESULTS: Compared with nonsmokers, both current and past smokers have reduced gonadotropin-stimulated ovarian function. A history of increasing tobacco exposure was associated with decreasing serum estradiol concentrations, numbers of retrieved oocytes, and numbers of embryos. On average, for every 10 pack-years of cigarette smoking, 2.5 fewer mature oocytes and 2.0 fewer embryos were obtained. Women who smoked during their treatment cycle had approximately a 50% reduction in implantation rate and ongoing pregnancy rate compared with women who had never smoked. Women who quit smoking before their treatment cycle had the same pregnancy rate as nonsmokers. CONCLUSION: Cigarette smoking is associated with a prolonged and dose-dependent adverse effect on ovarian function. Smoking appears to have a more transient toxic effect on fertility, because current smokers, but not past smokers, had a markedly reduced pregnancy rate after treatment cycles compared with nonsmokers. Women should quit smoking before assisted reproduction cycles.

Primary hypothyroidism associated with multicystic ovaries and ovarian torsion in an adult.

BACKGROUND: Primary hypothyroidism is known to be associated with multicystic ovaries in juvenile females, but this association has been reported only once previously in an adult. This report describes an unusual case of bilateral multicystic ovaries occurring in an adult patient with profound hypothyroidism. CASE: A 26-year-old woman presented with an acute abdomen and bilateral adnexal masses. An emergency exploratory laparotomy revealed bilateral enlarged multicystic ovaries with torsion of the right ovary. Because this ovary was necrotic, it was removed; pathology revealed multiple hemorrhagic follicular cysts. Laboratory studies to evaluate the cause of the multicystic ovaries revealed negative serum beta-hCG, LH 0.7 IU/L, FSH 15.7 IU/L, and estradiol 80 pg/mL. The TSH value was greater than 50 IU/L and serum thyroxine was undetectable, demonstrating profound hypothyroidism. Subsequent thyroid hormone replacement was associated with resolution of the cysts in the remaining ovary. CONCLUSION: Profound hypothyroidism can cause multicystic ovaries in an adult. In the absence of ovarian torsion, surgery can be avoided, as thyroid hormone replacement leads to clinical resolution of the cysts within 3 months.

Sonohysterography in premenopausal women with and without abnormal bleeding.

OBJECTIVE: To estimate the prevalence of abnormalities detected by sonohysterography in premenopausal women who were asymptomatic or had abnormal uterine bleeding. METHODS: Standard sonohysterography was done in 100 asymptomatic premenopausal women age 30 and older. The prevalence of uterine abnormalities was recorded and compared with findings in 80 premenopausal women evaluated in our unit for abnormal uterine bleeding. RESULTS: Compared with asymptomatic women, premenopausal women with abnormal uterine bleeding had a higher prevalence of polyps (33 versus 10%), intracavitary myomas (21 versus 1%), and intramural myomas (58 versus 13%). Ten percent of asymptomatic women had polyps, but these polyps tended to be smaller than the polyps found in women with abnormal bleeding (8.5 versus 13.9 mm, P = .064). Polyps were associated significantly with myomas, and both were more common in older premenopausal women. CONCLUSION: Intracavitary lesions and intramural myomas are more prevalent in women with abnormal uterine bleeding than in asymptomatic women, suggesting a causative relationship. However, small endometrial polyps are common and frequently asymptomatic.

Diurnal variations in midluteal serum progesterone measurements.

The utility of a single midluteal phase progesterone (P) value has been questioned by studies that document pulsatile P secretion. In this study, fluctuations of P values during clinical sampling times were investigated. Significant differences were found between morning and afternoon mean P values and in the timed occurrence of clinically relevant P values. Despite reported pulsatile secretion, the impact of clinically significant fluctuations may be minimized by the use of timed sampling.

A comparison of peritoneal fluid parameters of infertile patients and the subsequent occurrence of pregnancy.

The effects of peritoneal fluid or its cellular components on human oocyte fertilization and cleavage cannot be studied directly. This report explores the association of laparoscopically obtained peritoneal fluid volume, macrophage count, and concentration of 124 infertility patients and their first occurrence of pregnancy during a 2-year follow-up period. Endometriosis patients who achieved pregnancy had a significantly lower mean fluid volume than those remaining nonpregnant. In patients with endometriosis, a fluid volume significantly less than the mean for all endometriosis patients carries a significantly greater chance of pregnancy. The time required for the occurrence of pregnancy in patients with endometriosis appears influenced by peritoneal fluid volume. Peritoneal fluid of patients with endometriosis, via an as yet unknown mechanism or substance, appears to be associated with reduced fertility.

Peritoneal fluid environment and infertility.

The PF environment is one that hosts the processes of ovulation, gamete transportation, fertilization, and early embryonic development. The cellular and acellular constituents of this dynamic fluid are in a constant interactive state, being influenced by the physiologic events of the menstrual cycle and pelvic disease processes; these constituents probably influence disease manifestation and reproduction. The importance of understanding this zone of early reproductive life has been now recognized. We hope that future investigations will define the exact role(s) of known components and some yet-to-be defined substances of PF in disease processes that affect reproductive function. With better understanding of normal and abnormal events in this pelvic microenvironment, we can develop rationales for novel treatment modalities.

After superovulation-intrauterine insemination fails: the prognosis for treatment by gamete intrafallopian transfer/pronuclear stage transfer.

OBJECTIVE: To determine the prognosis for gamete intrafallopian transfer (GIFT)/pronuclear stage transfer (PROST) treatment after prior superovulation-intrauterine insemination (IUI). DESIGN: Matched, retrospective. SETTING: Outpatient university endocrine-infertility program. PATIENTS, PARTICIPANTS: One hundred forty-four women matched for infertility factors and age were studied according to the following three treatment groups: superovulation-IUI only, GIFT/PROST only, or GIFT/PROST after superovulation-IUI. MAIN OUTCOME MEASURES: Per cycle and cumulative pregnancy rates (PRs) were compared utilizing life table analysis. RESULTS: Cumulative PRs (0.408) for superovulation-IUI only were lower than initial (0.469) and cumulative (0.802) cycle fecundity of GIFT/PROST (P = 0.002). Per cycle and cumulative PRs did not differ between GIFT/PROST only versus GIFT/PROST after superovulation-IUI. CONCLUSIONS: Gamete intrafallopian transfer/PROST may be cost-effective when compared with superovulation-IUI. The prognosis for GIFT/PROST success is not negatively affected by earlier superovulation-IUI treatment failure.

Bilateral undescended ovaries: association with infertility and treatment with IVF.

OBJECTIVE: To describe the clinical findings in a patient with bilateral undescended ovaries and infertility who was successfully treated by IVF. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 35-year-old woman with bilateral undescended ovaries. INTERVENTION(S): Hysterosalpingography, laparoscopy, and an IVF cycle. MAIN OUTCOME MEASURE(S): Anatomic description and pregnancy test. RESULT(S): This patient conceived and delivered a twin gestation after laparoscopic retrieval of oocytes and transfer of two blastocysts. CONCLUSION(S): Bilateral undescended ovaries is a rare condition that can be associated with infertility but can be successfully treated by IVF.

Ovarian volume: a novel outcome predictor for assisted reproduction.

OBJECTIVE: To determine the potential of ovarian volume as a predictor of assisted reproduction outcomes. DESIGN: Retrospective chart review. SETTING: University-based assisted reproduction program. PATIENTS: One hundred eighty-eight women initiating their first cycle of assisted reproduction. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Pretreatment transvaginal ultrasound ovarian measurements were compared with subsequent ovulation induction parameters (peak E2, numbers of oocytes, and embryos) and cycle outcome (cancellation and pregnancy). RESULT: Total ovarian volume and volume of the smallest ovary were significant variables predicting peak E2 and numbers of oocytes and embryos. Total ovarian volume was a predictor of cycle cancellation and volume of the smallest ovary a predictor of clinical pregnancy. Large ovarian volumes are associated with good assisted reproductive technology outcomes whereas small ovarian volumes are associated with poor outcomes. CONCLUSION: Beyond maternal age, total ovarian volume, and volume of the smallest ovary are significant predictors of the success of assisted reproductive techniques.

Increased risk of monochorionic twinning associated with assisted reproduction.

OBJECTIVE: To determine the incidence of monochorionic twinning in pregnancies resulting from assisted reproduction technologies (ARTs). METHODS: We reviewed our experience with 218 ART pregnancies achieved over 3 years. All patients underwent transvaginal ultrasound 26 and 36 days after oocyte retrieval. The presence of two yolk sacs or two fetal poles within one sac suggested monochorionicity, and was confirmed by follow-up ultrasound and placental pathology. The various ARTs were compared to determine if any method had an increased incidence of monochorionicity compared to any other method. Statistical analysis was performed employing Chi Square analysis. RESULTS: The incidence of monochorionicity in all gestations was 3.2% (8 times background rate); among multiple gestations it was 9.8%. The rates of monochorionicity for each ART appeared similar. CONCLUSION: The incidence of monochorionic twinning is increased in pregnancies resulting from ART. Careful ultrasound evaluation of such pregnancies for monochorionicity is strongly recommended, both for planning of prenatal care and when considering a multifetal pregnancy reduction procedure.

Early diagnosis of ovarian torsion by color Doppler ultrasonography.

Ovarian torsion is often difficult to diagnose because of the nonspecific nature of the clinical findings. We report on the use of color Doppler ultrasonography in diagnosing early ovarian torsion. This technique provides a highly specific finding, the absence of blood flow to the ovary, that greatly facilitates the diagnosis of ovarian torsion.

Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization.

OBJECTIVE: To determine prognostic factors for achieving a pregnancy with intrauterine insemination (IUI) and IVF. To compare the effectiveness and cost-effectiveness of IUI and IVF based on semen analysis results. DESIGN: Retrospective cohort study. SETTING: Academic university hospital-based infertility center. PATIENT(S): One thousand thirty-nine infertile couples undergoing 3,479 IUI cycles. Four hundred twenty-four infertile couples undergoing 551 IVF cycles. INTERVENTION(S): IUI and IVF treatment. MAIN OUTCOME MEASURE(S): Multiple logistic regression analysis was used to assess the significance of prognostic factors including a woman's age, gravidity, duration of infertility, diagnoses, use of ovulation induction, and sperm parameters for predicting the outcomes of clinical pregnancy and live birth rate after the first cycle of IUI and IVF. The relative effectiveness and cost-effectiveness of these treatments were then determined based on sperm count results. RESULT(S): Female age, gravidity, and use of ovulation induction were all independent factors in predicting pregnancy after IUI. The average total motile sperm count in the ejaculate was also an important factor, with a threshold value of 10 million. For IVF, only female age was an important predictor for both clinical and ongoing pregnancy. When the average total motile sperm count was under 10 million, IVF with ICSI was more cost-effective than IUI in our clinic. CONCLUSION(S): An average total motile sperm count of 10 million may be a useful threshold value for decisions about treating a couple with IUI or IVF.

Effects of smoking on ovulation induction for assisted reproductive techniques.

OBJECTIVE: To determine the effects of smoking on ovulation induction for assisted reproductive techniques. DESIGN: Matched, retrospective, cohort study. SETTING: Outpatient University endocrine/infertility program. PATIENTS: Eighteen smokers and 36 nonsmokers: 2 nonsmokers matched to each smoker for age, weight, and history of ovarian surgery. MAIN OUTCOME MEASURES: During a stimulation cycle, the serum estradiol (E2) level, number of follicles, number of oocytes, number of embryos, and ampules of gonadotropins used were compared in the smoking versus the nonsmoking groups by Wilcoxon's signed rank test for paired data. Follicular fluid (FF), testosterone (T), androstenedione (A), E2, A:E2 ratios, and T:E2 ratios were measured and compared between groups by Mann-Whitney U-tests. RESULTS: Smokers had significantly lower serum E2 levels, fewer follicles, fewer oocytes retrieved, and fewer embryos per cycle than nonsmokers, despite equal amounts of gonadotropin administration. Follicular fluid obtained from mature follicles had a higher A:E2 ratio and a higher T:E2 ratio in smokers compared with nonsmokers. CONCLUSIONS: Smoking adversely affects ovulation induction parameters and alters the FF hormonal milieu.

The efficacy and cost effectiveness of embryo cryopreservation compared with other assisted reproductive techniques.

OBJECTIVE: To evaluate the efficacy and cost effectiveness of embryo cryopreservation compared with other assisted reproductive techniques (ARTs). DESIGN: Retrospective review of medical records and health care costs. SETTING: Tertiary care academic medical school ART program. PATIENTS: For determination of the efficacy of cryopreserved ET, we analyzed 610 patients undergoing the first 1,000 oocyte retrievals in our program. For determination of cost effectiveness, we analyzed the costs associated with 334 initiated ART cycles in 1992. MAIN OUTCOME MEASURES: The ongoing pregnancy rate (PR) per initiated cycle and per oocyte retrieval. The medical costs associated with each procedure. RESULTS: The transfer of cryopreserved embryos increased the ongoing PR per oocyte retrieval by 6.6%. Transfer of cryopreserved embryos was cost effective compared with other ARTs. The cost per delivery for cryopreserved ETs was between 25% and 45% that of a fresh cycle. CONCLUSIONS: Including embryo cryopreservation in an ART program can improve PRs and lower the ultimate cost per delivery.

Conditions of oocyte storage and use of noninseminated as compared with inseminated, nonfertilized oocytes for the hemizona assay.

OBJECTIVES: To examine differences in sperm binding to the zona and recovery of oocytes from the storage vessel after oocyte preservation for the hemizona assay (HZA) by the method currently in predominant use, salt storage at 4 degrees C, as compared with a new method that should allow for indefinite preservation of zona receptors, dimethylsulphoxide (DMSO)/sucrose in liquid nitrogen (-196 degrees C). A second objective was to compare sperm binding to noninseminated zona as opposed to zona from inseminated, nonfertilized oocytes and to examine whether differences in binding potential were related to the patient's fertilization rate from the cycle in which the oocytes for the HZA originated. DESIGN: Binding and recovery were evaluated after 1, 2, 3, 6, 9, 12, and 17 to 25 months of storage. SETTING: In vitro fertilization and andrology laboratories at the University of Iowa Hospitals and Clinics; academic tertiary care center. RESULTS: Binding of sperm was significantly lower for nonfertilized oocytes stored > 12 months in salt at 4 degrees C than for those stored in liquid nitrogen. Binding was similar after storage for 1, 2, 3, 6, 9, and 12 months. Oocyte recovery was significantly lower after storage in salt for > 12 months as compared with storage in liquid nitrogen. Greater variability in sperm binding was observed between matching zona halves of nonfertilized as compared with noninseminated oocytes. Nonfertilized oocytes also bound fewer total sperm than noninseminated oocytes. The number of sperm bound to noninseminated oocytes was not related to the patient's fertilization rate from the cycle in which the oocytes originated. However, significantly fewer sperm bound to the zona of nonfertilized oocytes when the oocyte originated from a cycle in which the patient's fertilization rate was > 50%. CONCLUSIONS: These results indicate that storage of oocytes in DMSO/sucrose in liquid nitrogen results in superior long-term (> 12 months) preservation of zona receptors for sperm binding and improves oocyte recovery as compared with salt storage at 4 degrees C. Although noninseminated oocytes appear to be optimal for use in the HZA, nonfertilized oocytes can be used successfully if the oocytes originate from an IVF cycle in which the fertilization rate is < or = 50%.

Cost-effective treatment of the infertile couple.

OBJECTIVE: To review the published literature on the cost-effective approach to infertility treatment. DESIGN: The literature on the economics and cost-effectiveness of infertility treatments was reviewed. Studies related to this topic were identified through MEDLINE. RESULT(S): Few cost-effectiveness studies about infertility treatment have been published. In the absence of tubal blockage and severe male factor, use of IUI and hMG-IUI is more cost-effective than IVF. In vitro fertilization is at least as cost-effective as tubal surgery. Although IVF costs are high, they fall well within the range of other accepted medical treatments and are below the general public's willingness to pay for these treatments. CONCLUSION(S): Cost-effectiveness analysis is an important means of improving quality of care while controlling costs. Further work regarding cost-effectiveness of treatments among different diagnostic groups is needed.