Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth.

OBJECTIVE: To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice. DESIGN: Decision-tree mathematical model with sensitivity analyses. SETTING: Not applicable. PATIENT(S): A simulated cohort of women wishing to delay childbearing until age 40 years. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cost per live birth. RESULT(S): Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from $55,060 to $39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to $61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes. CONCLUSION(S): In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth.

Timing luteal support in assisted reproductive technology: a systematic review.

OBJECTIVE: To summarize the available published randomized controlled trial data regarding timing of P supplementation during the luteal phase of patients undergoing assisted reproductive technology (ART). DESIGN: A systematic review. SETTING: Not applicable. PATIENT(S): Undergoing IVF. INTERVENTION(S): Different starting times of P for luteal support. MAIN OUTCOME MEASURE(S): Clinical pregnancy (PR) and live birth rates. RESULT(S): Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed because of a high degree of clinical heterogeneity with regard to the timing, dose, and route of P. Two studies compared P initiated before oocyte retrieval versus the day of oocyte retrieval and PRs were 5%-12% higher when starting P on the day of oocyte retrieval. One study compared starting P on day 6 after retrieval versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing P start times on the day of oocyte retrieval versus 2 or 3 days after retrieval showed no significant differences in pregnancy. CONCLUSION(S): There appears to be a window for P start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. Although some studies have suggested a potential benefit in delaying vaginal P start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define P start time for luteal support after ART.

Comparison of two simulation systems to support robotic-assisted surgical training: a pilot study (Swine model).

OBJECTIVE: To compare the efficacy of simulation-based training between the Mimic dV- Trainer and traditional dry lab da Vinci robot training. DESIGN: A prospective randomized study analyzing the performance of 20 robotics-naive participants. Participants were enrolled in an online da Vinci Intuitive Surgical didactic training module, followed by training in use of the da Vinci standard surgical robot. Spatial ability tests were performed as well. Participants were randomly assigned to 1 of 2 training conditions: performance of 3 Fundamentals of Laparoscopic Surgery dry lab tasks using the da Vinci or performance of 4 dV-Trainer tasks. Participants in both groups performed all tasks to empirically establish proficiency criterion. Participants then performed the transfer task, a cystotomy closure using the daVinci robot on a live animal (swine) model. The performance of robotic tasks was blindly assessed by a panel of experienced surgeons using objective tracking data and using the validated Global Evaluative Assessment of Robotic Surgery (GEARS), a structured assessment tool. RESULTS: No statistically significant difference in surgeon performance was found between the 2 training conditions, dV-Trainer and da Vinci robot. Analysis of a 95% confidence interval for the difference in means (-0.803 to 0.543) indicated that the 2 methods are unlikely to differ to an extent that would be clinically meaningful. CONCLUSION: Based on the results of this study, a curriculum on the dV- Trainer was shown to be comparable to traditional da Vinci robot training. Therefore, we have identified that training on a virtual reality system may be an alternative to live animal training for future robotic surgeons.

Progesterone luteal support after ovulation induction and intrauterine insemination: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of luteal phase P support after ovulation induction IUI. DESIGN: A systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Undergoing ovulation induction IUI. INTERVENTION(S): Any form of exogenous P in ovulation induction IUI cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth. RESULT(S): Five trials were identified that met inclusion criteria and comprised 1,298 patients undergoing 1,938 cycles. Clinical pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.15-1.98) and live birth (OR 2.11, 95% CI 1.21-3.67) were more likely in P-supplemented patients. These findings persisted in analyses evaluating per IUI cycle, per patient, and first cycle only data. In subgroup analysis, patients receiving gonadotropins for ovulation induction had the most increase in clinical pregnancy with P support (OR 1.77, 95% CI 1.20-2.6). Conversely, patients receiving clomiphene citrate (CC) for ovulation induction showed no difference in clinical pregnancy with P support (OR 0.89, 95% CI 0.47-1.67). CONCLUSION(S): Progesterone luteal phase support may be of benefit to patients undergoing ovulation induction with gonadotropins in IUI cycles. Progesterone support did not benefit patients undergoing ovulation induction with CC, suggesting a potential difference in endogenous luteal phase function depending on the method of ovulation induction.

Polycystic ovarian syndrome management options.

Polycystic ovarian syndrome (PCOS) is a disorder of androgen excess and ovarian dysfunction. Hirsutism and elevated free testosterone levels are the most consistent signs of the androgen excess. Irregular, infrequent, or absent menses and infertility are symptoms of ovulatory dysfunction. Obesity is also a feature of this syndrome and contributes to associated metabolic abnormalities. Lifestyle modification should be the first treatment and is effective in reducing the signs and symptoms. The ovulatory infertility associated with PCOS can be overcome in most cases with oral (clomiphene citrate or letrozole) or injectable (gonadotropins) agents. Surgical intervention is reserved for cases resistant to medical management.

Evaluation and treatment of anovulatory and unexplained infertility.

Anovulatory disorders are a primary cause of female infertility. Polycystic ovarian syndrome is the major cause of anovulation and is generally associated with obesity. Lifestyle changes to encourage weight loss are the initial therapy for overweight and obese patients, followed by clomiphene citrate for ovulation induction. For those patients who fail to ovulate on clomiphene citrate, alternatives, such as letrozole; gonadotropins; and complimentary agents to enhance clomiphene citrate, such as metformin and glucocorticoids, are reviewed. Women with unexplained infertility (no identifiable cause of infertility on a routine evaluation) may benefit from ovulation induction with clomiphene citrate, letrozole, or gonadotropins.

Effect of length of controlled ovarian hyperstimulation using a gonadotropin-releasing hormone antagonist on in vitro fertilization pregnancy rates.

OBJECTIVE: To compare pregnancy outcomes between shorter and longer in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles using GnRH antagonist protocol. STUDY DESIGN: Retrospective cohort analysis at a large military academic hospital. A total of 351 patients underwent 412 IVF/ICSI cycles using a GnRH antagonist protocol from September 2002 through May 2008. Clinical pregnancy and live birth rates for all IVF/ICSI cycles were compared independently for both total length of ovarian stimulation with gonadotropins (< 10 days vs. > or = 10 days) and GnRH antagonist use (< 4 days vs. > or = 4 days), respectively. RESULTS: Clinical pregnancy rates were 54.6% among cycles with total gonadotropin use <10 days vs. 48.6% for those cycles > or = 10 days, odds ratio 0.82 (0.53-1.27); live birth rates were 50.0% vs. 47.7%, odds ratio 0.91 (0.59-1.42). Clinical pregnancy rates were 54.0% among cycles with GnRH antagonist use < 4 days vs. 52.8% with GnRH antagonist use > or = 4 days, odds ratio 0.95 (0.62-1.45); live birth rates were 46.8% vs. 50.4%, odds ratio 1.15 (0.76-1.76). CONCLUSION: Clinical pregnancy and live birth rates are not adversely affected by longer IVF/ICSI cycles using GnRH antagonists.

Low-dose human chorionic gonadotropin may improve in vitro fertilization cycle outcomes in patients with low luteinizing hormone levels after gonadotropin-releasing hormone antagonist administration.

OBJECTIVE: To evaluate the effect of low levels of endogenous luteinizing hormone (LH) and low-dose human chorionic gonadotropin (hCG) supplementation on in vitro fertilization (IVF) cycle outcomes in a gonadotropin-releasing hormone (GnRH) antagonist protocol. DESIGN: Retrospective study. SETTING: Military medical center. PATIENT(S): General in vitro fertilization/embryo transfer (IVF-ET) population. INTERVENTION(S): Addition of low-dose urinary hCG to IVF stimulations using a recombinant follicle-stimulating hormone (FSH) and GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Implantation and live-birth rates. RESULT(S): As part of a larger cohort of 239 patients, 42 patients with LH levels ≤ 0.5 mIU/mL were evaluated. In the larger cohort, there were no differences in implantation and pregnancy rates between the recombinant FSH only (n = 113) and the recombinant FSH with low-dose hCG supplementation (n = 126) groups. In the FSH-only group, patients with LH levels ≤ 0.5 mIU/mL had decreased implantation rates (19% vs. 42%) and live-birth rates (25% vs. 54%) as compared with patients with LH levels >0.5 mIU/mL. Low LH patients in the recombinant FSH with low-dose urinary hCG group had statistically significantly higher implantation rates (54% vs. 19%) and live-birth rates (64% vs. 25%) as compared with patients with similar low LH levels in the recombinant FSH-only group. CONCLUSION(S): Endogenous LH levels ≤ 0.5 mIU/mL after GnRH antagonist treatment are associated with statistically significantly lower implantation and pregnancy rates in recombinant FSH-only cycles. The addition of low-dose urinary hCG results in improved implantation and live-birth rates in patients with low LH levels.

Recombinant follicle-stimulating hormone (rFSH) supplemented with low-dose human chorionic gonadotropin compared with rFSH alone for ovarian stimulation for in vitro fertilization.

Low-dose hCG supplementation was administered at the start of ovarian stimulation, concomitantly with recombinant FSH (rFSH) in GnRH antagonist cycles, and these were compared with GnRH-a cycles that used rFSH alone. The low-dose hCG group had similar implantation and pregnancy rates but had significantly reduced rFSH requirements, allowing for an average cost savings of $600 per cycle.

Establishing institutional critical values of follicle-stimulating hormone levels to predict in vitro fertilization success.

Elevated follicle-stimulating hormone (FSH) levels during the early follicular phase or in response to the clomiphene citrate challenge test indicate diminished ovarian reserve and poor reproductive potential. We performed a retrospective analysis of 413 infertile women, 23 to 40 years of age, who underwent 523 cycles of in vitro fertilization (IVF) to identify the critical FSH values that would predict a poor likelihood of success in our military IVF program. Each woman underwent a clomiphene citrate challenge test within 1 year of each IVF cycle. The overall live birth and implantation rates were 43% and 24%, respectively. The critical values for day 3 and day 10 FSH levels were 14.1 and 16.9 mIU/mL, respectively, with a 0% live birth rate and a 5% implantation rate above these levels. There were no differences in the live birth/implantation rates when stratified for FSH levels below the critical values. Medical centers offering IVF should determine their critical FSH values, to help identify patients unlikely to benefit from IVF and to ensure appropriate allocation of resources and realistic expectations for infertile couples.

Does the timing of mock embryo transfer affect in vitro fertilization implantation and pregnancy rates?

The timing of a mock embryo transfer does not affect in vitro fertilization implantation or pregnancy rates. Performing a mock embryo transfer at the time of oocyte retrieval, 3 to 5 days before embryo transfer, does not have a deleterious effect on the endometrium.

Intracervical block and pain perception during the performance of a hysterosalpingogram: a randomized controlled trial.

OBJECTIVE: To estimate whether an intracervical block of 1% lidocaine decreased pain perception compared with placebo during the performance of a hysterosalpingogram. METHODS: A randomized controlled trial was conducted with 120 patients assessing pain perception during a hysterosalpingogram. Patients were randomly assigned to one of three groups. Patients received either a 1% lidocaine intracervical block, an intracervical saline injection, or no injection. Visual analog (VAS) and qualitative scales were used to assess study participants' pain at six different time points during the hysterosalpingogram. RESULTS: Subjects receiving the lidocaine block had significantly less pain (P<.001) by VAS during tenaculum placement (approximately 61% less, 1.303 cm) and with tenaculum traction (approximately 40% less, 2.804 cm) compared with both the intracervical saline injection group and the no injection group (tenaculum placement, 3.384 cm and 3.354 cm, and tenaculum traction, 4.705cm and 4.961 cm, respectively). There was no improvement seen with pain perception during instillation of the contrast in the lidocaine group compared with the saline or no injection group (P<.073). Subjects who received the saline injection had statistically more pain (P<.001) by VAS (2.647 cm) immediately after the injection compared with the lidocaine (approximately 79% greater, 1.476 cm) and no injection groups (115% greater, 1.232 cm). CONCLUSION: Lidocaine intracervical block provides better pain relief than placebo during tenaculum placement and tenaculum traction during a hysterosalpingogram. This study suggests that patients should be offered an intracervical block before placement of the cervical tenaculum to decrease pain during the performance of a hysterosalpingogram. CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov), NCT00372658 LEVEL OF EVIDENCE: I.

Measuring estradiol levels after human chorionic gonadotropin administration for in vitro fertilization is not clinically useful.

A retrospective analysis of 844 IVF-ET cycles demonstrated that changes in E(2) levels after administration of hCG do not influence fertilization, implantation, pregnancy, or live-birth rates. In vitro fertilization cycles with a declining E(2) level have comparable success to those with no change or increasing E(2) levels and should proceed to oocyte retrieval.

A randomized controlled trial of increasing recombinant follicle-stimulating hormone after initiating a gonadotropin-releasing hormone antagonist for in vitro fertilization-embryo transfer.

OBJECTIVE: Pituitary suppression with a GnRH antagonist before IVF may result in a plateau or decrease in estradiol levels. We sought to investigate the effect of increasing recombinant FSH (rFSH) after starting a GnRH antagonist on estradiol levels, implantation rates, and pregnancy rates. DESIGN: Prospective, randomized multicenter study. SETTING: Military medical center and private practice. PATIENT(S): Sixty infertile women undergoing IVF who met the appropriate inclusion criteria. INTERVENTION(S): Participants were pretreated with combined oral contraceptives (COCs) and received a dose 150-300 IU of rFSH 5 days after taking their last COC. They were randomly assigned to receive their current dose of rFSH (control group) or an additional 75 IU of rFSH (step-up group) after starting a GnRH antagonist. Daily GnRH antagonist injections were started when the lead follicles were 13-14 mm in diameter and continued until hCG was given when two follicles were >or=18 mm. One to three embryos were transferred 3 or 5 days following oocyte retrieval. Women with PCOS, a body mass index >33, a day 3 FSH >14.1 mIU/mL, or prior poor stimulation were excluded. MAIN OUTCOME MEASURE(S): The primary endpoints of this pilot study were embryo implantation, pregnancy, and livebirth rates. Secondary endpoints included the amount and days of rFSH; number of days of GnRH antagonist use; estradiol levels on the day of GnRH antagonist initiation, day 1 and day 2 after initiation, and on the day of hCG; endometrial stripe thickness; number of follicles; and number of oocytes. RESULT(S): No differences were reported within the groups with respect to age, BMI, baseline FSH, use of intracytoplasmic sperm injection, vials of rFSH, number of GnRH antagonist injections, changes in estradiol patterns, or peak estradiol level. The control and step-up groups had similar pregnancies (73.3% vs. 63.3%, P=.41), clinical pregnancies (70.0% vs. 60.0%, P=.42), live births (56.7% vs. 60.0%, P=.8), and implantation rates (50.0% and 39.1%, P=.22). CONCLUSION(S): The use of rFSH and a GnRH antagonist in good candidates for IVF resulted in outstanding implantation and pregnancy rates. Increasing the dose of rFSH after starting a GnRH antagonist does not alter the estradiol response or improve the implantation and pregnancy rates.

Identifying women who will request sterilization reversal in a military population.

OBJECTIVE: We sought to identify the characteristics of women in a military population who are likely to seek a tubal anastomosis after a previous bilateral tubal ligation (BTL). METHOD: A written investigational review board-approved questionnaire was administered to 56 women, ages 18-40 years, requesting evaluation for a reversal of a prior BTL and 52 women of the same age range not seeking reversal. The questionnaire identified demographics and relationship characteristics of volunteers at the time of their decision to have a BTL and at the present time. RESULTS: Age 25 years or younger, sterilization due to pressure from a partner, poor marital relationship at the time of the BTL and a new marriage are highly predictive of tubal sterilization regret and a request for sterilization reversal in a military population. In addition, women requesting a tubal anastomosis reported less preoperative counseling on the permanence of a BTL and of the male alternative for permanent female sterilization, vasectomy. CONCLUSION: Women with these characteristics should have extensive counseling before undergoing tubal sterilization.

Tubo-ovarian abscess: diagnosis, medical and surgical management.

Tubo-ovarian abscess (TOA), a serious manifestation of pelvic inflammatory disease, has been treated with aggressive surgical therapy. With improvements in antibiotic therapy, laparoscopic surgery and interventional radiological techniques have lessened the need for radical surgical treatment in stable patients.

Efficacy of anti-tumor necrosis factor therapy in the treatment of spontaneous endometriosis in baboons.

OBJECTIVE: To determine the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in baboons. DESIGN: A randomized, placebo-controlled, blinded study using the baboon endometriosis model. SETTING: Southwest National Primate Research Center. ANIMAL(S): Twelve female baboons with spontaneous peritoneal endometriosis. INTERVENTION(S): Etanercept (n = 8) or sterile water (n = 4) was administered subcutaneously three times per week. MAIN OUTCOME MEASURE(S): After 8 weeks, the number, color, and surface area of peritoneal lesions was evaluated. Revised American Society for Reproductive Medicine staging was used. RESULT(S): A statistically significant decrease in red lesion surface area in the treatment group was observed. A trend toward a decrease in the absolute number of red lesions was noted in the treatment group. White and black lesion number and total surface area slightly increased in both groups but failed to achieve statistical significance. Endometriosis was diagnosed in 60% of captive-born baboons with primary infertility. CONCLUSION(S): These results indicate that etanercept effectively reduces the amount of spontaneously occurring active endometriosis in the baboon.

Granulocyte macrophage colony-stimulating factor in adenomyosis and autologous endometrium.

OBJECTIVE: Granulocyte macrophage colony-stimulating factor (GM-CSF) has been related to macrophage recruitment and activation and has been identified in the human endometrium. We determined whether adenomyosis expresses GM-CSF, and if present, compared GM-CSF protein expression in adenomyosis with that in autologous endometrium. METHODS: We examined ectopic and eutopic endometrium from 16 premenopausal women who had hysterectomies for abnormal uterine bleeding, pelvic pain, or uterine prolapse. Serial sections of premenopausal uteri containing endometrium and adenomyosis were analyzed by immunohistochemistry for GM-CSF ligand and receptor and CD68 macrophages. We analyzed the intensity of staining for GM-CSF ligand and receptor and macrophages in the glandular epithelium and stroma of adenomyosis and autologous endometrium. RESULTS: The GM-CSF ligand localized primarily in the glandular epithelium and myometrium with only light stromal staining. Staining for GM-CSF ligand was significantly higher in adenomyotic glands compared with autologous endometrial glands (P = .002), especially during the secretory phase of the menstrual cycle. There were no statistical differences in the amount and intensity of staining of the GM-CSF receptor in adenomyosis and autologous endometrium. Adenomyotic tissue contained significantly more macrophages than matched autologous endometrium (P = .0004). CONCLUSIONS: Adenomyotic glandular epithelium had greater expression of the GM-CSF ligand compared with autologous endometrium from premenopausal women, which indicates that GM-CSF may play a role in increasing the levels of activated macrophages in women with adenomyosis.