Treatment of intrauterine adhesions and subsequent pregnancy outcomes in an in-vitro fertilization population.

BACKGROUND: Asherman's syndrome refers to the presence of intrauterine adhesions which have clinical implications, including infertility. There are few studies in the literature assessing the effect of serial hysteroscopies for adhesiolysis on reproductive and pregnancy outcomes amongst women who subsequently undergo in-vitro fertilization (IVF), and none that have looked at maternal, neonatal or placental pregnancy complications. OBJECTIVE: This study aimed to explore the effect of hysteroscopic adhesiolysis amongst a cohort of patients who subsequently undergo IVF STUDY DESIGN: This was a retrospective cohort study of all patients who underwent hysteroscopic adhesiolysis for intrauterine adhesions at our center between 2005-2020, and subsequently attempted conception by IVF. A control group of patients who underwent IVF for non-uterine factor infertility and no prior history of intrauterine adhesions was chosen for comparison. RESULTS: There were 691 patients included in this study, of whom 168 were intrauterine adhesion cases. Implantation rate (41.3% in both groups), and live birth rate (aRR 0.93, 95% CI 0.76-1.14) were not statistically different between cases and controls. When grouped by number of previous adhesiolysis surgeries, patients who underwent 2 or more adhesiolysis surgeries did have a lower live birth rate compared to controls (aRR 0.53 (0.28-0.99). Endometrial thickness prior to transfer was significantly reduced in cases versus controls (8.23 vs 10.25mm, aRR 0.84; 95% CI 0.78-0.90). Adverse placental outcomes, including placenta accreta spectrum, placenta previa, or vasa previa, PP or vasa previa) were significantly more likely to occur in cases compared to controls (aRR 2.08; 95% CI 1.25-3.46). When grouped by number of prior adhesiolysis surgeries, the risk appeared to increase as the number of prior surgeries increased. This is likely due to the increased severity of these adhesions. CONCLUSIONS: Overall, patients with a history of treated intrauterine adhesions have the same live birth rate as patients undergoing IVF for non-uterine factor indications. However, the subgroup of patients who require multiple surgeries for correction of intrauterine adhesions do have a lower live birth rate after IVF compared to controls. Patients with a history of treated intrauterine adhesions are at significantly increased risk of placenta accreta syndrome disorder compared to controls who underwent IVF for non-uterine factor indications.

Association between oocyte retrieval technique and number of oocytes retrieved.

PURPOSE: To assess if there is an optimal oocyte retrieval (OR) technique to retrieve a maximum number of oocytes and mature oocytes (MII). METHODS: Retrospective cohort study in which nine physicians completed a survey on OR techniques. Number of oocytes/follicle cohort, MIIs/follicle cohort, and MIIs/oocytes retrieved (%MII) were assessed for each technique for patients undergoing OR from 3/2013 to 7/2019. Data were stratified by number of follicles on ultrasound on day of trigger (< 6, 6-10, > 10). RESULTS: Patient demographics were equivalent between techniques. For < 6 follicles, three techniques resulted in significantly fewer oocyte/follicle (0.97 ± 0.48, 0.95 ± 0.66, and 0.90 ± 0.41) compared to the top-performing technique (TPT) (1.11 ± 0.55). For 6-10 follicles, two techniques resulted in significantly fewer oocyte/follicle (0.95 ± 0.39 and 0.93 ± 0.35) compared to the TPT (1.06 ± 0.42). A different technique had higher %MII (0.77 ± 0.19) compared to two techniques (0.74 ± 0.21 and 0.72 ± 0.22). For > 10 follicles, two techniques resulted in significantly fewer oocyte/follicle (1.01 ± 0.42 and 1.07 ± 0.40) compared to the TPT (1.15 ± 0.41). These two techniques also resulted in fewer MII/follicle (0.75 ± 0.33 and 0.81 ± 0.34 vs. 0.87 ± 0.34). There was no consistent TPT across follicle number groups or for all outcome variables. CONCLUSIONS: There does not appear to be a clear TPT, even for patients with few follicles. Providers who perform OR in a similar fashion to physicians at our institution should feel confident that those techniques obtain equivalent oocyte yields.

Trans-implant treatment of chronic recurrent maxillary sinusitis via dynamic implants with an internal port: Experience with 31 cases.

This study was performed to test a protocol for trans-implant treatment of chronic recurrent maxillary sinusitis (CRS), via implants with an internal removable sealing screw. The appropriate indications for treatment, optimal number of treatment sessions, and general schedule of treatment and follow-up were assessed. This was a retrospective study of 31 patients with CRS who were managed with trans-implant lavage. Of these patients, 28 (referred for a sinus elevation procedure) underwent a simultaneous implantation procedure and treatment of the sinusitis. Three patients received treatment for sinusitis via an already existing implant. The suggested sinusitis treatment protocol includes the drainage of pus through the punctured sinus floor and three sessions of antral irrigation/lavage, four cone beam computed tomography scans, and four transnasal endoscopic observations. The suggested combined protocol includes the simultaneous evaluation of the implant status and the sinusitis treatment results on days 30 and 60 after surgery. Of the 31 patients, 28 (90%) had complete relief of most of their symptoms (nasal obstruction/discharge, anosmia/hyposmia) up to day 30 postoperative. Follow-up nasal endoscopy demonstrated no evidence of active sinus disease. Twenty-seven implants were well-osseointegrated and were still in use for prosthetic purposes. In one case, the implantation failed because of poor bone quality. For the remaining 30 cases, both clinical and radiological results showed stability of the implants and no CRS recurrence during the whole follow-up period. The dental implant with an internal central port and an integral sealing screw may be used for drainage, irrigation, observation, and further treatment of the maxillary sinus in cases of CRS.

A novel rat model for assessment of laryngotracheal injury following transoral intubation.

OBJECTIVE: Laryngotracheal damage is a well-described complication of endotracheal intubation and animal models are essential for studying the underlying cellular injury cascade. This novel rat model is based on transoral intubation and aims to simulate the common clinical scenario of tube-related airway damage. METHODS: Prospective randomized control pilot study. 28 male Sprague-Dawley were randomly assigned into three groups: control, 3-h' intubation and 6-h' intubation. The animals were then euthanized and their laryngotracheal complexes sent for histological analysis. Epithelial damage, mucosal thickness and mucosal gland hypertrophy were reviewed. RESULTS: Total of 13 control animals and 15 intubated animals. 10 intubated animals survived the study protocol. Loss of epithelial surface architecture including damage to the microscopic ciliary mechanism was a common feature amongst all intubated animals. Average mucosal thickness of the larynx (including vocal cords and subglottic area) was 143 ±â€¯88 µm for control rats, 315 ±â€¯101 µm for rats intubated 3 h and 574 ±â€¯174 µm for rats intubated 6 h .This was a statistically significant difference. Average mucosal gland hypertrophy in the laryngeal subsite was 0.41 ±â€¯0.5 in control rats, 1.4 ±â€¯0.5 in rats intubated 3 h and 2.0 ±â€¯0.0 for rats intubated 6 h (statistically significant difference). There was a clear difference between three and 6 h of intubation with poorer mucosal injury parameters for longer intubation. CONCLUSIONS: We describe a novel rat-based animal model for simulating airway mucosal damage following transoral intubation. This animal model is easy to carry out, reproducible and involves containable animal mortality rates.

Responses to fertility treatment among patients with cancer: a retrospective cohort study.

BACKGROUND: Cancer treatments have significant negative impacts on female fertility, but the impact of cancer itself on fertility remains to be clarified. While some studies have shown that compared with healthy women, those with cancer require higher doses of gonadotropins resulting in decreased oocyte yields, others have shown comparable oocyte yields between the two groups. The purpose of this study is to evaluate whether there is an association between any cancer and/or type of cancer, and response to ovarian stimulation for egg and embryo banking. METHODS: In this retrospective cohort study, ovarian stimulation cycles performed from June 2007 through October 2014 at a single academic medical center were reviewed to identify those undertaken for women with cancer undergoing fertility preservation (n = 147) or women with no cancer undergoing their first cycle due to male factor infertility (n = 664). Of the 147 women undergoing fertility preservation, 105 had local cancer (Stage I-III solid malignancies) and 42 had systemic cancer (hematologic or Stage IV solid malignancies). Response to ovarian stimulation was compared among these two groups and women with no cancer. RESULTS: Adjusting for age and BMI, women with systemic cancer had lower baseline antral follicle counts (AFC) than women with no cancer or local cancer. Women with systemic cancer required higher doses of FSH than women with no cancer or local cancer, and they had higher oocyte to AFC ratios than women with no cancer or local cancer, but greater odds of cycle cancellation as compared to women with no cancer or local cancer. No significant differences were observed among the three groups for duration of stimulation, number of oocytes and mature oocytes retrieved, or number of embryos created. CONCLUSIONS: Women with cancer achieve similar oocyte and embryo yields as women with no cancer, although those with systemic cancer require higher FSH doses and are at greater risk of cycle cancellation.

The effect of short-term exposure of cumulus-oocyte complexes to in vitro maturation medium on yield of mature oocytes and usable embryos in stimulated cycles.

PURPOSE: We examined whether short-term exposure to in vitro maturation (IVM) medium of cumulus-oocyte complexes (COCs) from a stimulated cycle increases the yield of metaphase II (MII) oocytes and usable embryos. METHODS: Retrospective review of two consecutive autologous IVF/ICSI cycles per patient between 2007 and 2015 in which cycle 1 did not result in live birth. Patients with short-term exposure of COCs to IVM medium (3-5 h before standard insemination or ICSI) in cycle 2 (treated) were matched 1:4 on %MI and %MII to patients without use of IVM in cycle 2 (untreated). The proportions of mature oocytes, two pronucleate (2PN) zygotes, number of usable embryos, and clinical outcomes were compared between groups with regression modeling. RESULTS: The treated (n = 43) and untreated (n = 163) groups had similar demographic characteristics and similarly high proportions of immature oocytes (48.2 vs. 41.3%, respectively) in cycle 1. There were no significant differences between the treated and untreated groups in the change in %MII (48.1 to 68.9% vs. 50.5 to 72.5%, respectively) or mean number of usable embryos (2.2 to 3.4 vs. 2.0 to 3.3, respectively) from cycle 1 to cycle 2. CONCLUSIONS: These findings suggest that short-term IVM incubation of COCs may not provide any additional benefit in patients with a prior unsuccessful cycle notable for a high proportion of immature oocytes. Further randomized studies are warranted to determine whether there is a subset of patients who may have improved clinical outcomes with this "rescue IVM" intervention.

Dilute versus concentrated vasopressin administration during laparoscopic myomectomy: a randomised controlled trial.

OBJECTIVE: To determine if higher-volume, fixed-dose administration of vasopressin further reduces blood loss at the time of minimally invasive myomectomy. DESIGN: Randomised multicentre clinical trial. SETTING: Tertiary-care academic centres in the USA. POPULATION: Women undergoing conventional laparoscopic or robot-assisted laparoscopic myomectomy. METHODS: All participants received the same 10-unit (U) dose of vasopressin, but were randomly assigned to one of two groups: (i) received 200 ml of diluted vasopressin solution (20 U in 400 ml normal saline), and (ii) received 30 ml of concentrated vasopressin solution (20 U in 60 ml normal saline). MAIN OUTCOME MEASURES: The primary study outcome was estimated blood loss; the study was powered to detect a 100-ml difference. RESULTS: A total of 152 women were randomised; 76 patients in each group. Baseline demographics were similar between groups. The primary outcome of intraoperative blood loss was not significantly different, as measured by three parameters: surgeon estimate (mean estimated blood loss 178 ± 265 ml and 198 ± 232 ml, dilute and concentrated groups respectively, P = 0.65), suction canister-calculated blood loss, or change in haematocrit levels. There were no vasopressin-related adverse events. CONCLUSION: Both dilute and concentrated vasopressin solutions that use the same drug dosing demonstrate comparable safety and tolerability when administered for minimally invasive myomectomy; however, higher volume administration of vasopressin does not reduce blood loss. TWEETABLE ABSTRACT: This randomised trial failed to show benefit of high-volume dilute vasopression.

Building a model to increase live birth rate through patient-specific optimization of embryo transfer day.

PURPOSE: Many practices are moving away from cleavage-stage transfer in favor of blastocyst transfer. The purpose of this study is to evaluate how the overall live birth rate for fresh IVF cycles may increase by optimizing the day of transfer for each patient. METHODS: This is a retrospective cohort study of 1225 first fresh autologous IVF cycles performed between May 2012 and November 2013. Stepwise logistic regression was used to determine characteristics associated with live birth following cleavage-stage versus blastocyst transfer. The optimal transfer day (i.e., the day that maximized the odds of live birth) was determined for each patient, and the actual live birth rate was compared with the projected rate had each patient undergone transfer on her optimal day. RESULTS: With transfer on the optimal day for each patient, the overall birth rate would have increased from its actual value of 34.8 % to a projected 43.0 %, a 24 % increase. The majority of this increase (21 %) was due to optimization of patients who underwent cleavage-stage transfer but had a higher projected birth rate from blastocyst transfer. These patients were older (37.8 versus 36.0 years, p < 0.01) and had more follicles ≥18 mm than patients who should have remained with a cleavage-stage transfer. CONCLUSIONS: A model can be built enabling patient-specific identification of optimal transfer day; within this discovery cohort, such optimization was estimated to increase live birth following a fresh transfer by 24 %. This study suggests blastocyst transfer should be more widely offered; however, there remain patients for whom a cleavage-stage transfer may yield better outcomes.

Graftless sinus augmentation with simultaneous dental implant placement: clinical results and biological perspectives.

After a sinus lifting procedure, the compartment around the implants under the sinus mucosal lining in the sinus floor is filled with a blood clot from surrounding bleeding. The aim of this study was to evaluate the feasibility of bone formation following graftless sinus lifting with the simultaneous placement of dental implants. Thirty graftless sinus lifting procedures were performed and 72 dental implants placed in 18 consecutive patients, using the lateral window approach. Clinical and radiological follow-up was conducted throughout the 6-month healing period. Biopsies of 30 cases were collected at 6 months post-treatment: 15 biopsies were taken from the newly formed bone near the basal floor and 15 from the newly formed bone near the elevated membrane. New bone consolidation in the maxillary sinus was apparent radiologically and histologically at 6 months after sinus augmentation, providing an average 6.14±1.34mm of bone-gain. Based on histological analysis and histomorphometric data, the consolidated bone in the augmented sinus comprised 56.7±11.9% to 59.9±13.4% vital bone tissue. Out of the 72 implants placed, only four failed, indicating a 94% overall implant survival rate. Based on this case series, blood clot can be considered autologous osteogenic graft material, to which osteoprogenitors can migrate, differentiate, and regenerate bone.

Temporomandibular joint arthroscopy technique using a single working cannula.

The traditional arthroscopy technique includes the creation of three ports in order to enable visualization, operation, and arthrocentesis. The aim of this study was to assess an advanced temporomandibular joint (TMJ) arthroscopy technique that requires only a single cannula, through which a one-piece instrument containing a visualization canal, irrigation canal, and a working canal is inserted, as an alternative to the traditional double-puncture technique. This retrospective study assessed eight patients (13 TMJs) with pain and/or limited range of movement that was refractory to conservative therapy, who were treated between June 2015 and December 2015. The temporomandibular joint disorder (TMD) was diagnosed by physical examination and mouth opening measurements. The duration of surgery was recorded and compared to that documented for traditional arthroscopies performed by the same surgeon. Operative single-cannula arthroscopy (OSCA) was performed using a holmium YAG (Ho:YAG) 230µm fibre laser for ablation. The OSCA technique proved effective in improving mouth opening in all patients (mean increase 9.12±1.96mm) and in reducing pain (mean visual analogue scale decrease of 3.25±1.28). The operation time was approximately half that of the traditional technique. The OSCA technique is as efficient as the traditional technique, is simple to learn, and is simpler to execute.

Compensatory Increase in Ovarian Aromatase in Older Regularly Cycling Women.

CONTEXT: Serum estradiol (E2) levels are preserved in older reproductive-aged women with regular menstrual cycles despite declining ovarian function. OBJECTIVE: The objective of the study was to determine whether increased granulosa cell aromatase expression and activity account for preservation of E2 levels in older, regularly cycling women. DESIGN: The protocol included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle. SUBJECTS: Healthy, regularly cycling older (36-45 y; n = 13) and younger (22-34 y; n = 14) women participated in the study. MAIN OUTCOME MEASURES: Hormone levels were measured in peripheral blood and follicular fluid aspirates and granulosa cell CYP19A1 (aromatase) and FSH-R mRNA expression were determined. RESULTS: Older women had higher FSH levels than younger women during the early follicular phase with similar E2 but lower inhibin B and antimullerian hormone levels. Late follicular phase serum E2 did not differ between the two groups. Follicular fluid E2 [older (O) = 960.0 [interquartile range (IQR) 765.0-1419.0]; younger (Y) = 994.5 [647.3-1426.5] ng/mL, P = 1.0], estrone (O = 39.6 [29.5-54.1]; Y = 28.8 [22.5-42.1] ng/mL, P = 0.3), and the E2 to testosterone (T) ratio (O = 109.0 ± 41.9; Y = 83.0 ± 18.6, P = .50) were preserved in older women. Granulosa cell CYP19A1 expression was increased 3-fold in older compared with younger women (P < .001), with no difference in FSH-R expression. CONCLUSIONS: Ovarian aromatase expression increases with age in regularly cycling women. Thus, up-regulation of aromatase activity appears to compensate for the known age-related decrease in granulosa cell number in the dominant follicle to maintain ovarian estrogen production in older premenopausal women.

Computer-assisted reproductive surgery: microsurgery for the digital age.

Although considerable progress has been made in the field of medically assisted reproduction, minimally invasive surgery remains of vital importance in optimizing and preserving fertility, as well as treating infertility. By definition, reproductive surgery employs microsurgical techniques with the objective of restoring natural fertility or enhancing assisted reproductive technologies. The avant-garde minimalist philosophy of this branch of gynecology has made it the natural trailblazer of laparoscopic surgery. Minimally invasive conservative treatment of uterine, tubal, ovarian and peritoneal pathology has long been the gold standard for women of reproductive age and those seeking fertility preservation. Robust surgical outcome data acknowledge clear advantages of advanced laparoscopic surgery over laparotomy. However, this comes at the cost of significant technical challenges. Computer-assisted laparoscopy, also known as robotic surgery, is posed to address the practical limitations of conventional laparoscopic surgery and bridge this technical gap. This enabling technology is a conceptual fusion of the practicality of conventional open surgery and the minimally invasive nature of laparoscopic surgery. With this comes the promise of simplifying complex minimally invasive fertility-sparing procedures so that they can be performed in a safe and reproducible manner by reproductive specialists.

Evidence that increased ovarian aromatase activity and expression account for higher estradiol levels in African American compared with Caucasian women.

CONTEXT: Serum estradiol levels are significantly higher across the menstrual cycle in African American (AAW) compared with Caucasian women (CW) in the presence of similar FSH levels, yet the mechanism underlying this disparity is unknown. OBJECTIVE: The objective of the study was to determine whether higher estradiol levels in AAW are due to increased granulosa cell aromatase mRNA expression and activity. DESIGN: The design of the study included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle. SUBJECTS: Healthy, normal cycling AAW (n = 15) and CW (n = 14) aged 19-34 years participated in the study. MAIN OUTCOME MEASURES: Hormone levels in peripheral blood and follicular fluid (FF) aspirates and aromatase and FSH receptor mRNA expression in granulosa cells were measured. RESULTS: AAW had higher FF estradiol [1713.0 (1144.5-2032.5) vs 994.5 (647.3-1426.5) ng/mL; median (interquartile range); P < .001] and estrone [76.9 (36.6-173.4) vs 28.8 (22.5-42.1) ng/mL; P < .001] levels than CW, independent of follicle size. AAW also had lower FF androstenedione to estrone (7 ± 1.8 vs 15.8 ± 4.1; mean ± SE; P = .04) and T to estradiol (0.01 ± 0.002 vs 0.02 ± 0.005; P = .03) ratios, indicating enhanced ovarian aromatase activity. There was a 5-fold increase in granulosa cell aromatase mRNA expression in AAW compared with CW (P < .001) with no difference in expression of FSH receptor. FSH, inhibin A, inhibin B, and AMH levels were not different in AAW and CW. CONCLUSIONS: Increased ovarian aromatase mRNA expression, higher FF estradiol levels, and decreased FF androgen to estrogen ratios in AAW compared with CW provide compelling evidence that racial differences in ovarian aromatase activity contribute to higher levels of estradiol in AAW across the menstrual cycle. The absence of differences in FSH, FSH receptor expression, and AMH suggest that population-specific genetic variation in CYP19, the gene encoding aromatase, or in factors affecting its expression should be sought.

Uterine length and fertility outcomes: a cohort study in the IVF population.

STUDY QUESTION: What is the relationship between pre-cycle uterine length and IVF outcome (chemical pregnancy, clinical pregnancy, spontaneous abortion and live birth)? SUMMARY ANSWER: Women at extremes of uterine length (<7.0 or >9.0 cm) were less likely to achieve live birth and women with uterine lengths <6.0 cm were also more likely to experience spontaneous abortion. WHAT IS KNOWN ALREADY: A prospective study of 807 women published in 2000 found that implantation and clinical pregnancy rates were highest in women with uterine lengths between 7.0 and 9.0 cm, though the difference was not significant. The relationship between pre-cycle uterine length and live birth has not been evaluated. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of all cycles performed after uterine length measurement at an academic hospital IVF clinic from 2001 to 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 8981 fresh cycles were performed in 5120 adult women with normal uterine anatomy. Women with uterine anomalies (unicornuate, bicornuate, septate or uterus exposed to diethylstilbestrol) were excluded and women with fibroids were identified for subanalysis. Uterine length was measured by uterine sounding. Cycles were divided by uterine length into groups: <6.0 cm (very short, n = 76), 6.0-6.9 cm (short, n = 2014), 7.0-7.9 cm (referent, n = 4984), 8.0-8.9 cm (long, n = 1664) and ≥9 cm (very long, n = 243). Multivariate logistic regression (first-cycle analyses) and generalized estimating equations (all-cycle analyses) were adjusted for age, fibroids and ART treatment (assisted hatching, intracytoplasmic sperm injection) to generate relative risk (RR) of cycle outcomes by uterine length. MAIN RESULTS AND THE ROLE OF CHANCE: Median uterine length in the IVF population was 7.0 cm (interquartile range 7.0-7.8) and was positively associated with BMI (P < 0.001) and fibroids (P = 0.02). Compared with the referent group, women with uterine lengths <6.0 cm were half as likely to achieve live birth (RR: 0.53; 95% confidence interval (CI): 0.35-0.81) and women with lengths of 6.0-6.9 cm were also less likely (RR: 0.91; CI: 0.85-0.98). Cubic regression spline identified a significant inverse U-shaped association whereby women with uterine lengths <7.0 or >9.0 cm were less likely to achieve live birth. Women with lengths <6.0 cm were also more likely to experience spontaneous abortion (RR: 2.16; CI: 1.23-3.78). Results remained consistent when excluding women with a uterine factor diagnosis (n = 8823), when limiting to the first cycle at our institution (n = 5120) and when further restricting to first-ever cycles (n = 3941). LIMITATIONS, REASONS FOR CAUTION: Optimal assessment of uterine length by ultrasound was not feasible due to time and cost limitations, though uterine sounding is a clinically relevant measurement allowing for results with practical implications. Findings from our predominantly Caucasian clinic population may not be generalizable to infertile populations with different ethnic compositions. WIDER IMPLICATIONS OF THE FINDINGS: Reproducibility of results would solidify findings and inform patient counseling in women undergoing IVF. STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for this investigation. MD declares relationships with UpToDate (royalties) and WINFertlity (consultant).