Premature Ovarian Insufficiency After Coronavirus Disease 2019 (COVID-19): Autoimmune Follicle-Stimulating Hormone (FSH) and FSH Receptor Blockade.

BACKGROUND: Since the onset of the coronavirus disease (COVID-19) pandemic, a variety of long-COVID-19 symptoms and autoimmune complications have been recognized. CASES: We report three cases of autoimmune premature poor ovarian response in patients aged 30-37 years after mild to asymptomatic COVID-19 before vaccination, with nucleotide antibody confirmation. Two patients failed to respond to maximum-dose gonadotropins for more than 4 weeks, despite a recent history of response before having COVID-19. After a month of prednisone 30 mg, these two patients had normal follicle-stimulating hormone (FSH) levels, high oocyte yield, and blastocyst formation in successful in vitro fertilization cycles. All three patients have above-average anti-müllerian hormone levels that persisted throughout their clinical ovarian insufficiency. Two patients had elevated FSH levels, perhaps resulting from FSH receptor blockade. One patient, with a history of high response to gonadotropins 75 international units per day and below-normal FSH levels, had no ovarian response to more than a month of gonadotropins (525 international units daily), suggesting autoimmune block of the FSH glycoprotein and possible FSH receptor blockade. CONCLUSION: Auto-antibody production in response to COVID-19 before vaccination may be a rare cause of autoimmune poor ovarian response. Although vaccination is likely protective, further study will be required to evaluate the effect of vaccination and duration of autoimmune FSH or FSH receptor blockade.

Insulin Resistance and ß-cell Function Calculated by Homeostasis Model Assessment in Lean, Overweight, and Obese Women with Polycystic Ovary Syndrome.

OBJECTIVE: To evaluate the homeostasis model assessment (HOMA) measurement of insulin resistance (IR) and pancreatic ß-cell function (%ß) and compare those values between groups of healthy-weight, over-weight, and obese women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Retrospective cohort study of women aged 24-48 with PCOS, diagnosed according to 2004 Rotterdam criteria. Participants were grouped by BMI. Quantitative variables were compared by one-way ANOVA and the Tukey method. Analysis for power to detect a difference between means was conducted. Pearson correlation was used to test differences in frequency distribution. RESULTS: By BMI category, 29 participants were of healthy weight, 11 were overweight, and 11 were obese. HOMA-IR was significantly higher in obese women as compared to overweight and healthy-weight patients (2.88 ± 2.09, 1.13 ± 0.73, 0.84 ± 0.49, respectively; p <0.0001). Moreover, HOMA-%ß was significantly increased in obese women as compared to overweight and healthy-weight patients (186.89 ± 131.62, 106.83 ± 46.77, 86.60 ± 40.91, respectively; p<0.0001). Adequate statistical power was not present to distinguish a difference between overweight and normal-weight participants. A positive linear correlation was found between log HOMA-IR and BMI, and between log HOMA-%ß and BMI. CONCLUSION: Obese PCOS patients have a higher risk of elevated insulin resistance and ß-cell function than do those with BMI <30.

Sonohysterographic predictors of successful hysteroscopic myomectomies.

BACKGROUND AND OBJECTIVES: The purpose of this study is to assess the rate of persistent submucosal myomas and intrauterine scarring after hysteroscopic myomectomy, as well as to evaluate the preoperative and intraoperative sonohysterographic findings that will predict persistence of myomas, scarring, and the need for repeat surgery. METHODS: Charts from all hysteroscopic myomectomies performed by a single surgeon between 2003 and 2011 were reviewed for preoperative, intraoperative, and postoperative sonohysterographic findings. Predictors included myoma number, diameter and percent extension into the cavity of the largest fibroid, and percent surgically resected. These predictors were assessed with postoperative sonohysterography. Statistics included t test, logistic regression, χ(2) test, and Fisher exact test. RESULTS: Among the 79 cases with postoperative sonohysterograms, 17 (21.5%) had persistent submucosal myoma, and 9 (11.4%) had intrauterine scarring on postoperative sonohysterogram. Repeat hysteroscopic myomectomy was required in 11 (13.9%), but none required lysis of adhesions. The myoma number was not a significant predictor. A higher percentage of myoma within the cavity (63.35% vs 44.89%, P < .05) and smaller myoma size (2.22 cm vs 3.31 cm, P < .01) were significant predictors of a complete resection, a normal postoperative sonohysterogram, and avoidance of repeat surgery. On regression analysis, the percent of the myoma resected was the most significant outcome predictor (P < .001). CONCLUSION: Larger myomas with a lower percent found within the uterine cavity are less likely to be completely resected. Percent resection at the time of surgery is the most significant predictor of a normal postoperative sonohysterogram, as well as the best predictor of the need for repeat surgery.

Blastulation rates decline in a linear fashion from euploid to aneuploid embryos with single versus multiple chromosomal errors.

OBJECTIVE: To test the hypothesis that the blastulation rate is higher in euploid embryos than in aneuploid embryos as assessed by cleavage-stage biopsy with array-comprehensive genomic hybridization (aCGH). DESIGN: Retrospective cohort study. SETTING: University-affiliated institution. PATIENT(S): Forty-one patients with 48 in vitro fertilization (IVF) cycles and 385 embryos that underwent cleavage-stage preimplantation genetic screening (PGS) with aCGH at the Continuum Reproductive Center between January 2010 and September 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Probability of blastocyst and/or fully expanded or hatching blastocyst (FEHB) progression depending on number of chromosomal abnormalities. RESULT(S): Euploid embryos are twice as likely to progress to blastocyst and three times as likely to progress to FEHB than aneuploid embryos: 76% versus 37% and 56% versus 18%, respectively. For every additional chromosomal abnormality, the likelihood of progressing to the blastocyst stage decreases by 22% and the likelihood of progressing to FEHB decreases by 33%. CONCLUSION(S): Euploid embryos are far more likely than aneuploid embryos to progress to the blastocyst and FEHB stages. There is a linear decrease in probability of blastulation with the increasing number of chromosomal abnormalities.

Positive Chlamydia trachomatis serology result in women seeking care for infertility is a negative prognosticator for intrauterine pregnancy.

BACKGROUND: There are no prior studies that assess the non-in vitro fertilization (IVF) pregnancy rates in chlamydia serology-positive versus serology-negative women. Therefore, we wanted to determine whether a positive Chlamydia trachomatis immunoglobulin G serology result predicts reduced clinical pregnancy rates without IVF. METHODS: A prospective observational study was performed at a university-affiliated reproductive center. A total of 1279 new infertility patients seen at the Continuum Reproductive Center between January 2007 and June 2009 underwent C. trachomatis immunoglobulin G screening. Charts were later reviewed for hysterosalpingography, laparoscopy, treatment cycles, and ultrasound evidence of an intrauterine pregnancy. The main outcome measure was non-IVF cumulative pregnancy rates. RESULTS: Seventy (5.5%) of 1279 of the participants were found to have a positive chlamydia serology result. Serology-positive participants had significantly more tubal block on hysterosalpingography (37.5% vs. 10.1%, P = 0.001) and laparoscopically confirmed tubal damage (85.7% vs. 48.9%, P = 0.002). The percent of all participants who achieved an ultrasound documented clinical pregnancy, at our center, without IVF was significantly lower among Chlamydia-positive participants (10.0% versus 21.7%) in seronegative participants (P < 0.02). The hazard rate of non-IVF clinical pregnancy among chlamydia antibody testing-positive patients was 57% less than the rate of pregnancy among chlamydia antibody testing-negative patients (hazard ratio, 0.43; 95% confidence interval, 0.20-0.92). Both the per-cycle and the cumulative IVF pregnancy rates were equivalent in seropositive and in seronegative participants. CONCLUSIONS: This is the first large study to report that a positive serology screening result is both predictive of tubal damage and a reduced cumulative pregnancy rate when excluding treatment with IVF.

Preimplantation genetic screening (PGS) with Comparative genomic hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages.

PURPOSE: To determine benefits of cleavage-stage preimplantation genetic screening (PGS) by array comparative genomic hybridization (CGH). METHODS: A retrospective case-control study was performed at a tertiary care university-affiliated medical center. Implantation rate was looked at as a primary outcome. Secondary outcomes included clinical and ongoing pregnancy rates, as well as multiple pregnancy and miscarriage rates. Thirty five patients underwent 39 fresh cycles with PGS by aCGH and 311 similar patients underwent 394 invitro fertilization cycles. RESULT(S): The implantation rate in the CGH group doubled when compared to the control group (52.63 % vs. 19.15 %, p = < 0.001), clinical pregnancy rate was higher (69.23 % vs. 43.91 %, p = 0.0002), ongoing pregnancy rate almost doubled (61.54 % vs. 32.49 %, p = < 0.0001), multiple pregnancy rate decreased (8.33 % vs. 34.38 %, p = 0.0082) and miscarriage rate trended lower (11.11 % vs. 26.01 %, p = 0.13). CONCLUSION: Cleavage stage PGS with CGH is a feasible and safe option for aneuploidy screening that shows excellent outcomes when used in fresh cycles. This is the first report of cleavage stage PGS by CGH showing improved ongoing pregnancy rates.

Elevated progesterone-to-estradiol ratio versus serum progesterone alone for predicting poor cycle outcome with in vitro fertilization.

OBJECTIVE: To determine whether a progesterone-to-estradiol (P/E2) ratio on day of human chorionic gonadotropin (hCG) administration would be a better predictor of in vitro fertilization (IVF) outcome than serum P alone. STUDY DESIGN: All 348 fresh IVF cycles performed in 2002 and 2003 at a university hospital center were reviewed for all cycle parameters as related to the peak P and peak P/E2 ration on day hCG administration. RESULTS: Out of the 348 cycles performed, 199 cycles resulted in clinical pregnancies. The mean P level (1.4 ng/mL) was equivalent in both conception and nonconception cycles. A P/E2 ratio > 1.0, however, was associated with a highly significant reduction in clinical pregnancy rate (38.2% vs. 62.6%, p< 0.01) and live birth rate (35.4% vs. 49.1%, p = 0.02). CONCLUSION: Cycles with elevated P/E2 ratios are associated with lower clinical pregnancy and live birth rates, which decrease further as the P/E2 ratio rises. P/E2 ratio improves the prediction of IVF outcome when compared to serum P levels alone.

Fresh MESA improved embryo fertilization, cleavage, blastula formation and implantation rates after failed TESA in couples with obstructive azoospermia.

PURPOSE: To determine whether our use of fresh MESA cycles improved outcomes in patients with obstructive azoospermia who had failed IVF with TESA. METHODS: A prospective observational trial of couples undergoing IVF for obstructive azoospermia was performed at an academic IVF center. RESULTS: When TESA resulted in poor embryo cleavage, implantation and ongoing pregnancy rates, subsequent fresh MESA cycles in these same couples, demonstrated dramatic improvement in cleavage, blastulation, implantation and live birth rates. CONCLUSIONS: In patients undergoing IVF-TESA-ICSI with obstructive azoospermia resulting in poor cleavage rates, blastulation rates and cycle failure, a repeat cycle with MESA may result in marked improvement in outcome.

A comparison of gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist flare protocols for poor responders undergoing in vitro fertilization.

OBJECTIVE: To compare stimulation profiles, pregnancy, and live birth rates in poor responders during in vitro fertilization (IVF) cycles using either a gonadotropin-releasing hormone (GnRH) antagonist (cetrorelix) or a GnRH agonist flare protocol (leuprolide). DESIGN: Retrospective chart review. SETTING: A university-affiliated IVF program. PATIENT(S): Women designated as poor responders based on a prior stimulation cycle or baseline follicle-stimulating hormone (FSH) level of >10 mIU/mL, who needed at least 375 IU of starting daily gonadotropins in the study cycle. INTERVENTION(S): Administration of GnRH agonist flare or GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate. RESULT(S): For 68 GnRH antagonist and 45 GnRH agonist flare cycles, the groups were similar with respect to age (38.8 versus 38.6 years) and basal FSH concentration (8.33 versus 8.65 mIU/mL). No statistically significant differences between the protocol types were noted in peak estradiol levels, amount of gonadotropins used, number of oocytes obtained, or embryos transferred. The pregnancy rates (40% versus 45.2%) and live birth rates (27.7% versus 31.7%) in the GnRH antagonist and flare groups, respectively, were similar. CONCLUSION(S): We achieved excellent and comparable pregnancy and live birth rates in poor responders of advanced reproductive age with the use of either GnRH antagonist or flare protocol.

A 5-mm open-entry technique achieves safe, single-step, cosmetic laparoscopic entry.

BACKGROUND AND OBJECTIVE: The rare but serious complications of blind Veress needle insertion during laparoscopy include bowel and vascular injury. To reduce these risks, a novel method of open laparoscopy was introduced into our clinical practice, and its efficacy was evaluated. METHODS: This is a retrospective evaluation of a novel 5-mm-open laparoscopic technique in a university hospital-based endoscopy practice in 65 consecutive patients undergoing laparoscopy with a single surgeon. RESULT: A 71% success rate was achieved using the 5-mm open-entry laparoscopic technique. No complications occurred during any of the laparoscopic procedures, but 29% reverted to a standard 5-mm Veress needle technique. The success of the open-entry technique was independent of prior abdominal surgery, subject age, or body mass index (BMI). CONCLUSION: The 5-mm open-entry technique is safe, fast, and cosmetic. It is easily mastered and may be converted to a standard Veress needle technique if peritoneal entry is not achieved.

Comparison of FSH flare with and without pretreatment with oral contraceptive pills in poor responders undergoing in vitro fertilization.

OBJECTIVE: To compare FSH, LH, estrogen, and P flare response following 1 mg lupron injection in poor responders with or without pretreatment with oral contraceptive pills (OCPs). DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Poor responders undergoing IVF flare protocol from October 2002 to November 2003. INTERVENTION(S): Patients were divided into group A, who received OCPs before IVF cycle (n = 12), and group B, who did not (n = 7). One milligram Lupron was injected SC after measuring day 2 serum FSH, LH, estrogen, and P. After 24 hours, serum hormones were measured before lupron administration. MAIN OUTCOME MEASURE(S): Serum FSH, LH, estrogen, and P before and after 1 mg lupron RESULT(S): Basal FSH was similar in both groups (8.6 +/- 4.5 vs. 9.6 +/- 2.9 mIU/mL). Group A patients had significantly lower day 2 FSH (3.6 +/- 3.6 vs. 10.1 +/- 4.2 mIU/mL; P<.05). After lupron, although both groups had a significant rise in FSH and LH, mean LH rise in group B was 39.5 +/- 31 mIU/mL versus 11.3 +/- 4.6 mIU/mL in group A (P<.05). CONCLUSION(S): Pretreatment with OCPs in GnRH agonist flare protocol suppresses pre-Lupron FSH but does not blunt FSH flare. It blunts LH flare, which may be beneficial.

Predictors of embryo fragmentation and outcome after fragment removal in in vitro fertilization.

OBJECTIVE: To assess predictors of embryo fragmentation in IVF as well as to compare cycle outcomes between low-grade embryos subjected to defragmentation and high-grade embryos not undergoing defragmentation. DESIGN: A retrospective, case-control trial. SETTING: A university hospital IVF program. PATIENT(S): Three hundred twenty-seven nondonor, fresh IVF cycles. MAIN OUTCOME MEASURE(S): Predictors of fragmentation. We evaluated age, basal FSH and E(2) levels, the number of retrieved oocytes, and fertilization rates. Outcome assessments following defragmentation included rates of implantation, clinical pregnancy, spontaneous abortion, and live birth. RESULT(S): Increased age and lower number of oocytes and embryos were associated with embryo fragmentation. Lower-grade embryos after defragmentation yielded rates of implantation, clinical pregnancy, live birth, spontaneous abortion, and fetal defects equivalent to high-grade embryos. CONCLUSION(S): Fragmented embryos correlate with poorer prognosis cycles; however, fragmented embryos that undergo defragmentation result in equivalent clinical outcomes to high-grade, nondefragmented embryos.

Chlamydia serology screening in infertility patients.

A prospective study of 210 infertile patients, investigating the role of chlamydia serology as a screening test for tubal infertility with comparison of results with hysterosalpingography and laparoscopy, showed that Chlamydia serology is an inexpensive, noninvasive test that matches or surpasses the predictive value of most standard infertility tests.

Prospective randomized trial of right-sided paracolic adhesiolysis for chronic pelvic pain.

BACKGROUND: Prior study has shown that right paracolic adhesions are found in 90% of patients with chronic pelvic pain and less frequently in pain-free patients. We set out to determine whether paracolic adhesiolysis will reduce site-specific pain. METHODS: This was a prospective, randomized trial of right paracolic adhesiolysis at the time of diagnostic and operative laparoscopy for chronic pelvic pain. Twenty-five patients with a diagnosis of chronic pelvic pain were randomized to either undergo or withhold lysis of right paracolic adhesions at the time of operative laparoscopy. RESULTS: Right paracolic adhesions were found in 100% of our patients. For all subjects, there was a significant reduction of right and left lower quadrant pain (P<0.001) following the operative laparoscopy. Those who underwent right paracolic adhesiolysis had significantly greater right pelvic pain reduction than those who did not (P=0.014). There was no difference in the reduction of left or mid pelvic pain between the treatment and control groups. CONCLUSIONS: Right paracolic adhesiolysis reduces short-term site-specific tenderness in patients with chronic pelvic pain. Patients who would benefit from diagnostic or operative laparoscopy are likely to benefit further from paracolic adhesiolysis.