Embryo blastulation and quality between days 5 and 6 of extended embryo culture.

PURPOSE: This study aims to know what proportion of culture day 5 pre-blastocyst-stage embryos develop into blastocysts by culture day 6 and what patient and cycle characteristics are associated with delayed blastocyst formation. METHODS: A retrospective observational cohort analysis was performed including a total of 9886 embryos from 1008 IVF cycles in 835 patients, who underwent treatment between January 1, 2016, and December 31, 2018. Autologous fresh in vitro fertilization (IVF) cycles at a single academic center were included in the analysis. Embryos were group-cultured using single-step culture media. Blastulation was defined as the presence of a new blastocyst. Usable blastulation was defined as the presence of a new good or excellent quality, expanded, hatching, or hatched blastocysts. RESULTS: The mean blastulation rate between days 5 and 6 of extended embryo culture was 30.9%. The mean percentage of embryos developing into usable blastocyst-stage embryos was 19.8%. The factors associated with blastulation on day 6 included the total number of embryos and the number of pre-blastocysts on day 5, as well as the use of ICSI. Age, the number of total embryos, those remained in culture and pre-blastocysts, as well as the blastulation rate on day 5 were associated with usable blastulation. CONCLUSION: It is important to know the usable blastocyst development rate between culture days 5 and 6 in order to adequately counsel patients debating whether to proceed with fresh ET on day 5 or forego ET with the expectation that embryos will be biopsied for PGT and/or cryopreserved on culture day 6. Our findings provide evidence to help guide patients in this difficult decision.

Live birth and multiple birth rates in US in vitro fertilization treatment using donor oocytes: a comparison of single-embryo transfer and double-embryo transfer.

OBJECTIVE: To compare live birth rates (LBRs) and multiple birth rates (MBRs) between elective single-embryo transfer (eSET) and double-embryo transfer (DET) in donor oocyte in vitro fertilization (IVF) treatments in both a cycle-level and clinic-level analysis. METHODS: Donor oocyte IVF treatments performed by US IVF clinics reporting to the Centers for Disease Control and Prevention in 2013-2014 were included in the analysis. Primary outcomes included LBR and MBR. Secondary outcomes included gestational age at delivery (GA) and birth weight (BW) of offspring. These outcomes were evaluated on an individual cycle level as well as on the clinic level. RESULTS: In multivariable models, LBR did not change significantly as clinics utilized eSET more frequently. MBR decreased significantly as utilization of eSET increased, from 39% MBR in clinics that utilized eSET 0-9% of the time to 7% MBR in clinics that used eSET 70% of the time (P < .0001). Mean BW and GA of IVF-conceived offspring both increased as clinics utilized eSET more frequently (2778 to 3185 g [P < .0001] and 37.5 to 38.5 weeks [P = .02] for clinics with the lowest and highest eSET utilization, respectively). CONCLUSIONS: US IVF clinics utilizing eSET with higher frequencies have clinically comparable LBRs and significantly lower MBRs than clinics with lower-frequency eSET utilization. Mean offspring BW and GA increased with higher eSET utilization, further confirming the improved safety of this practice.

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.

Progression of atypical endometrial hyperplasia to adenocarcinoma despite intrauterine progesterone treatment with the levonorgestrel-releasing intrauterine system.

BACKGROUND: Intrauterine progesterone therapy has been proposed as a potential uterine-sparing treatment for atypical endometrial hyperplasia and adenocarcinoma. CASE: We present a case of an infertility patient with atypical endometrial hyperplasia who was treated with the levonorgestrel-releasing intrauterine system for 6 months. At follow-up, she was noted to have an increasing endometrial thickness on ultrasonography, and biopsy revealed progression of her lesion to adenocarcinoma. CONCLUSION: Although there is a need for uterine-sparing treatment for atypical endometrial hyperplasia and early adenocarcinoma, especially in the setting of desired fertility, caution should be exercised. We do not recommend using the levonorgestrel-releasing intrauterine system as a treatment for atypical hyperplasia or adenocarcinoma until further studies demonstrate the efficacy of this treatment.

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.

Expression and localization of luteinizing hormone receptor in the female mouse reproductive tract.

The presence of the LH receptor (LHR) in nongonadal tissues of the reproductive tract has been reported, but localization studies have not been performed. Our objectives were to demonstrate the presence of LHR in the reproductive tract and to localize receptor expression. Reproductive age rats and mice were obtained and (125)I-hCG binding assays were performed on membrane preparations from the uterus, ovary, liver, and testis. In situ hybridizations were performed using (35)S-labeled antisense and sense RNA probes prepared from nucleotides 1-591 of the mouse LHR cDNA. Specific hCG binding was detected in membrane preparations from the ovary, uterus, and testis but not in the liver in both the rat and mouse. In the ovary, LHR mRNA was localized in theca cells, large follicles, and corpora lutea as expected. In the uterus, LHR mRNA was expressed in stromal cells of the endometrium and in the uterine serosa. Uterine smooth muscle cells had low levels of expression, and the endometrial epithelium was negative. In the oviduct, high levels of LHR expression were noted on the serosa and in subepithelial cells. Oviductal smooth muscle had low expression, and the epithelium was negative. We conclude that functional, nongonadal LHR are expressed in the mouse reproductive tract. The presence and localization of LHR expression in the mouse reproductive tract lay the foundation for transgenic models to address the physiologic role of these receptors.

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.

Treatment of endometrial polyps.

OBJECTIVE: To determine the effectiveness of different treatments for abnormal uterine bleeding in women with known endometrial polyps. METHODS: We retrospectively assessed the effectiveness of polypectomy and other treatments of women with abnormal uterine bleeding who had benign polyps detected by sonohysterography. Women with endometrial polyps diagnosed by sonohysterography between January 1997 and July 1998 were sent questionnaires on pretreatment and posttreatment uterine bleeding and satisfaction with their treatments. Charts were reviewed to validate questionnaire responses and determine treatments administered. RESULTS: Seventy-eight women had endometrial polyps by sonohysterography, and 60 of them (77%) responded to the questionnaire. Two with endometrial adenocarcinoma were excluded. The average age of the remaining 58 was 49 years; 37 (64%) were premenopausal and 21 (36%) postmenopausal. The average time from treatment to follow-up was 13 months (range 5-24 months). Participants were grouped according to the following treatments: polypectomy, polypectomy plus endometrial ablation, polypectomy plus hysteroscopic myomectomy, hysterectomy, D&C, and nonsurgical treatment. The most frequent treatment was polypectomy (n = 26). Polypectomy, polypectomy plus endometrial ablation, polypectomy plus myomectomy, and hysterectomy each resulted in at least a twofold decrease in the number of bleeding days per month and led to high satisfaction rates. CONCLUSION: Our results showed that simple polypectomy and more invasive surgical procedures led to subjective improvement in symptoms of menorrhagia and metrorrhagia and a high satisfaction rate in women with endometrial polyps.

Cost-effective treatment for the couple with infertility.

Although the evaluation of cost-effective approaches to infertility treatment remains in its infancy, several important principles have emerged from the initial studies in this field. Currently, in treating couples with infertility without tubal disease or severe male-factor infertility, the most cost-effective approach is to start with IUI or superovulation-IUI treatments before resorting to IVF procedures. The woman's age and number of sperm present for insemination are significant factors influencing cost-effectiveness. The influence of certain diagnoses on the cost-effectiveness of infertility treatments requires further study. Even when accounting for the costs associated with multiple gestations and premature deliveries, the cost of IVF decreases within the range of other cost-effective medical procedures and decreases to less than the willingness to pay for these procedures. Indeed, for patients with severe tubal disease, IVF has been found to be more cost-effective than surgical repair. The cost-effectiveness of IVF will likely improve as success rates show continued improvements over the course of time. In addition, usefulness of embryo selection and practices to reduce the likelihood of high-order multiple pregnancies, without reductions in pregnancy rates, will significantly impact cost-effectiveness. The exclusion of infertility treatments from insurance plans is unfortunate and accentuates the importance of physicians understanding the economics of infertility treatment with costs that are often passed directly to the patient. The erroneous economic policies and judgments that have led to inequities in access to infertility health care should not be tolerated.

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.

Ovarian volume may predict assisted reproductive outcomes better than follicle stimulating hormone concentration on day 3.

This study was undertaken to compare ovarian volume with other factors which are important for the success of assisted reproduction. The first treatment cycle for 261 patients meeting all entry criteria between September 1993 and June 1995 was considered. All cycles employed the same stimulation protocol and no interventions were based upon pre-treatment indicators. Pre-treatment ovarian volumes, cycle day 3 follicle stimulating hormone (FSH) and oestradiol concentrations, smoking status and age were compared to subsequent peak oestradiol concentrations, numbers of oocytes retrieved, cycle cancellation and occurrence of clinical pregnancy. Statistical evaluation was performed using simple and multiple logistic regression analysis to determine odds ratios. The resultant odds ratios suggest that age and small ovarian volume may predict retrieval of fewer mature oocytes, while the failure to achieve clinical pregnancy was predicted by current smoking and small ovarian volume. Day 3 FSH values failed to be a significant predictor when maternal age, smoking status and ovarian volume were known. It can be concluded that, like maternal age and smoking status, ovarian volume may be a clinically important predictor of reproductive success, being superior to cycle day 3 FSH or oestradiol concentrations as an assessment of ovarian reserve.

Establishment of a successful donor embryo program: medical, ethical, and policy issues.

OBJECTIVE: To determine how couples prefer to dispose of their extra embryos and to establish a donor embryo program for the treatment of infertile couples. DESIGN: Cohort study. SETTING: University-based IVF program. PATIENT(S): Patients (n = 365) with cryopreserved embryos in storage for >2 years and eight patients who desired donated embryos for transfer. INTERVENTION(S): An IVF ethics committee was formed to discuss the ethical and policy issues involved in starting an embryo donation program and to establish program guidelines. Couples with embryos cryopreserved for > or = 2 years were contacted to determine their desires for disposition of embryos. Potential recipients of donated embryos were identified in our clinic, and donated embryos were transferred to these patients. MAIN OUTCOME MEASURE(S): Desires for embryo disposition and pregnancy rates. RESULT(S): Most couples elected either to continue storage of their embryos for future use (44%) or to discard their embryos (34%). A minority elected to donate their embryos either to infertile couples (11%) or for research (10%). Eight couples have had donated embryos transferred, and four have conceived ongoing pregnancies. CONCLUSION(S): Although only a small percentage of couples are willing to donate their embryos, the resulting number of embryos for use is substantial. Transfer of donated embryos results in a high pregnancy rate and is a cost-effective treatment of infertility.

Malignant cervical schwannoma: An unusual pelvic tumor.

BACKGROUND: Primary malignant cervical schwannomas (malignant peripheral nerve sheath tumors) are extremely rare tumors that grossly may resemble many other more common lesions. The diagnosis, management, and follow-up of a malignant cervical schwannoma are presented with a review of the literature. CASE: A 51-year-old female presented with a 3-year history of perimenopausal vaginal bleeding. A 3 x 3 cm friable, spongy lesion was noted on the posterior aspect of the cervix. Frozen-section analysis could not rule out a malignant smooth muscle tumor. The patient underwent an exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. Immunohistochemistry and electron microscopy aided in the final diagnosis of a malignant cervical schwannoma. The patient is alive and well 1 year from her definitive surgery. Another patient with the same tumor received the same surgical management. This patient is now 10 years from her surgery and is alive with no evidence of disease. CONCLUSION: Immunohistochemistry and electron microscopy are useful in the diagnosis of a malignant cervical schwannoma. This case and long-term follow-up from another case provide evidence that simple hysterectomy may be sufficient therapy for this uncommon lesion.

Messenger ribonucleic acid for the gonadal luteinizing hormone/human chorionic gonadotropin receptor is not present in human endometrium.

OBJECTIVE: To determine whether messenger RNA for the gonadal LH/hCG receptor is present in human endometrium with the use of reverse-transcriptase polymerase chain reaction. DESIGN: In vitro experiment. SETTING: Academic medical center. PATIENT(S): Premenopausal women who were not receiving hormonally active medications and who were undergoing hysterectomy for uterine leiomyomas, menorrhagia, pelvic pain, or uterine prolapse. INTERVENTION(S): Tissue from hysterectomy specimens was processed for RNA and treated with deoxyribonuclease where appropriate, and RNA was reverse-transcribed to complementary DNA. MAIN OUTCOME MEASURE(S): An appropriately sized band after reverse-transcriptase polymerase chain reaction, followed by sequencing to confirm the results. RESULT(S): A primer pair that spanned the extracellular domain was unable to amplify receptor complementary DNA from human endometrial tissue. For a primer pair that spanned transmembrane regions 2-6 of the receptor and was contained wholly in exon 11, a 552-base pair fragment was amplified successfully in 19 of 25 human endometrial samples. CONCLUSION(S): The traditional gonadal LH/hCG receptor does not appear to be present in human endometrial tissue. The presence of a portion of the transmembrane part of the molecule suggests that human endometrium may express a truncated or variant form of the receptor.

Intermenstrual bleeding secondary to cesarean scar diverticuli: report of three cases.

BACKGROUND: The differential diagnosis of intermenstrual bleeding includes structural lesions of the endometrium and cervix. CASES: Discrete diverticuli were noted in the endocervical canals of three women presenting with histories of multiple cesareans and chief complaints of intermenstrual bleeding. On ultrasound, diverticuli were diagnosed as cavities filled with heterogeneous material consistent with blood. In one case, the diverticulum was also visualized on hysterosalpingogram. Hysterectomy specimens in two cases showed diverticuli lined with fibrous tissue in previous uterine scars; in one case, this also contained endometrium. CONCLUSION: Uterine scar diverticuli may cause intermenstrual bleeding in women with previous cesareans. When performing ultrasound in this clinical setting, physicians should look for these defects.

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.

Selective early elimination of luteal support in assisted reproduction cycles using a gonadotropin-releasing hormone agonist during ovarian stimulation.

OBJECTIVE: To determine if women undergoing GnRH agonist-hMG stimulated IVF cycles can undergo successful discontinuation of luteal phase support. DESIGN: A protocol for selective discontinuation of luteal phase support was evaluated prospectively in women undergoing assisted reproduction cycles. SETTING: A tertiary care institutional-based assisted reproduction program. PATIENT(S): One hundred eighty-eight women who conceived after an IVF or zygote intrafallopian transfer cycle including a GnRH agonist between January 1994 and June 1997. INTERVENTION(S): Women with serum progesterone levels of > or = 60 ng/mL at 4 weeks' gestation were selected for discontinuation of their luteal phase support. MAIN OUTCOME MEASURE(S): Delivery rate. RESULT(S): Sixty-three women (62.4%) met the criteria for discontinuation of luteal phase support. There were no differences in the mean age, peak E2 levels, number of follicles, number of embryos transferred, or delivery rates (85.7% versus 78.9%) between the women who did and those who did not have discontinuation of their progesterone supplementation. CONCLUSION(S): These data reveal that luteal phase support can be discontinued successfully for selective women undergoing IVF who are receiving a GnRH agonist.