Creating affiliations, learning, and mindfulness for in vitro fertilization patients (CALM IVF): a clinical trial.

Objective: Determine if group psychoeducational support can improve in vitro fertilization (IVF) patients' quality of life (QoL). Design: Randomized controlled trial (NCT04048772). Setting: University-affiliated IVF clinic. Patients: Women (n = 76) and male partners undergoing initial autologous IVF cycle from August 2019, to December 2020. Interventions: Couples were assigned to groups based on projected oocyte retrieval date. Groups were randomly assigned to the control or intervention arm. Clinic closures because of the COVID-19 pandemic delayed treatment for a portion of participants. Groups were conducted in person before and virtually during the pandemic. Main Outcome Measures: The primary outcome was a change in fertility quality of life (FertiQoL) from baseline to 3 days after retrieval. Secondary outcomes were changes in depression (Patient Health Questionnaire 9), anxiety (Generalized Anxiety Disorder 7), resilience (Connor-Davidson Resilience scale), IVF knowledge scores, and the likelihood of return to treatment. Results: Knowledge scores among women in Creating Affiliations, Learning, and Mindfulness (CALM) for IVF groups significantly increased compared with control (mean difference 13.19 [3.53 - 22.84]) before the pandemic. During the pandemic, women in CALM IVF had significant improvement in the social FertiQoL score compared with controls (10.42 [1.79 - 19.04]). Compared with controls, male CALM IVF participants had significantly greater improvement in total FertiQoL (mean difference 6.68 [0.39 - 12.98]), treatment FertiQoL (8.26 [0.69 - 15.82]), and resilience (Connor-Davidson 1.13 [0.54 - 1.72]). Immediate return to care did not significantly differ between arms. Conclusions: For women undergoing IVF, group psychoeducational programs can improve IVF knowledge and social QoL during a pandemic. Participation in a group psychoeducational program can improve QoL and resilience in IVF dyad male partners. Clinical Trial Registration Number: Trial registration NCT04048772.

Cumulative live birth rate in women aged ≤37 years after in vitro fertilization with or without preimplantation genetic testing for aneuploidy: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System retrospective analysis.

Objective: To investigate cumulative live birth rates (CLBRs) in cycles with and without preimplantation genetic testing for aneuploidy (PGT-A) among patients aged <35 and 35-37 years. Design: Retrospective cohort study. Setting: Society for Assisted Reproductive Technology reporting clinics. Patients: A total of 31,900 patients aged ≤ 37 years with initial oocyte retrievals between January 2014 and December 2015 followed through December 2016. Interventions: None. Main outcome measures: The primary outcome was CLBR among patients aged <35 and 35-37 years. The secondary outcomes included multifetal births, miscarriage, preterm birth, perinatal mortality, and the time to pregnancy resulting in a live birth. Adjusted odds ratios (aORs) adjusting for age, body mass index, total 2 pronuclei embryos, embryos transferred, and follow-up timeframe. Results: Among patients aged <35 years, PGT-A was associated with reduced CLBRs (70.6% vs. 71.1%; aOR, 0.82; 95% CI [confidence interval], 0.72-0.93). No association was found between PGT-A and CLBRs among patients aged 35-37 years (66.6% vs. 62.5%; aOR, 0.92; 95% CI, 0.83-1.01). Overall, there was no significant difference in the miscarriage rate (aOR, 0.97; 95% CI, 0.82-1.14). Multifetal birth rates were lower with PGT-A (9.5% vs. 23.1%); however, PGT-A was not an independent predictor of multifetal birth (aOR, 1.11; 95% CI, 0.91-1.36). The average time to pregnancy resulting in a live birth was 2.37 months (SD 3.20) for untested transfers vs. 4.58 months (SD 3.53) for PGT-A transfers. Conclusions: In women aged <35, the CLBR was lower with PGT-A than with the transfer of untested embryos. In women aged 35-37 years, PGT-A did not improve CLBRs.

Dual trigger protocol is an effective in vitro fertilization strategy in both normal and high responders without compromising pregnancy outcomes in fresh cycles.

OBJECTIVE: To study the birth rates of normal vs. high responders after dual trigger of final oocyte maturation with gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin in fresh in vitro fertilization (IVF) cycles in which ovarian stimulation was achieved by a flexible GnRH antagonist protocol. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: In women <35 years of age, 290 fresh IVF cycles using the dual trigger protocol with day 5 embryo transfers from January 2013 to July 2018 were included. Cycles excluded were those with preimplantation genetic testing, gestational carriers, donor oocytes, and fertility preservation. INTERVENTIONS: IVF with dual trigger. MAIN OUTCOME MEASURES: Clinical pregnancy rate, live birth rate. RESULTS: Comparing normal responders, defined as <30 oocytes retrieved, and high responders, defined as ≥30 oocytes retrieved, the clinical pregnancy rates (67.0% vs. 69.3%, respectively) and live birth rates (60.5% vs. 60.0%, respectively) were not significantly different. No cases of ovarian hyperstimulation syndrome were reported in either group. CONCLUSIONS: Ovarian stimulation by a flexible GnRH antagonist protocol followed by dual trigger yields comparable outcomes between normal and high responders in fresh IVF cycles.

Elective transfer of one embryo is associated with a higher cumulative live birth rate and improved perinatal outcomes compared to the transfer of two embryos with in vitro fertilization.

OBJECTIVE: To compare the effects of initial elective single embryo transfer (ieSET) and initial double embryo transfer (iDET) strategies on the cumulative live birth rate (CLBR) and perinatal outcomes after IVF. DESIGN: Retrospective cohort study. SETTING: Society for Assisted Reproductive Technology (SART) reporting clinics. PATIENTS: 49,333 patients with initial oocyte retrievals between January 2014 and December 2015. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was CLBR, defined as up to 1 live birth resulting from a retrieval cycle and linked transfer cycles. Secondary outcomes included cycles to pregnancy, multifetal delivery rate, infant birthweight, and perinatal mortality rate. RESULTS: Compared to iDET, ieSET was associated with increased CLBR (74% vs. 57%; adjusted odds ratio [AOR], 1.32; 95% CI, 1.26-1.38). When stratified by age, the same trend was seen in all age categories, with statistical significance for those <38 years of age. ieSET was associated with reduced multifetal delivery (8% vs. 34%; AOR, 0.13; 95% CI, 0.12-0.14), increased birthweight (mean difference, 406 grams; 95% CI, 387-425), reduced preterm births (1.2% vs. 2.8%), and reduced perinatal mortality (0.5% vs. 1.2%). Compared with iDET, ieSET was associated with slightly more embryo transfer cycles (1.7 vs. 1.4 cycles; AOR, 1.19; 95% CI, 1.16-1.21) to achieve a pregnancy resulting in live birth. CONCLUSIONS: The association of ieSET with a higher CLBR and markedly improved perinatal outcomes outweigh the relatively minor increase in time to pregnancy, reinforcing the guidance for eSET in initial transfer cycles, particularly in younger patients with a good prognosis.

The effect of weight and body mass index on serum progesterone values and live birth rate in cryopreserved in vitro fertilization cycles.

OBJECTIVE: To determine if weight or body mass index (BMI) affects the serum progesterone level at the time of the pregnancy test in cryopreserved blastocyst transfer cycles and to determine if those serum progesterone levels affect live births. DESIGN: Retrospective cohort study. SETTING: US academic medical center. PATIENTS: Six hundred thirty-three patients undergoing their first cryopreserved embryo transfer cycle. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was the serum progesterone level on the day of the pregnancy test by patient weight and BMI. Our secondary analysis assessed the serum progesterone effect on live birth rate (LBR) in a clinic where progesterone supplementation was increased if the progesterone level was <15 ng/mL on the day of the pregnancy test. RESULTSS: There was a strong negative correlation between serum progesterone level and both BMI and weight, with BMI accounting for 27% and weight accounting for 29% of the variance in progesterone level. Serum progesterone level on the day of the pregnancy test was <15 ng/mL in 3% of women weighing <68 kg compared with 29% of women weighing ≥90.7 kg. Among women weighing ≥90.7 kg, live birth occurred in 47% whose serum progesterone level was <15 ng/mL on the day of the pregnancy test compared with 49% in those with serum progesterone level of 15-19 ng/mL and 44% in those with serum progesterone level of ≥20 ng/mL. CONCLUSIONS: Body weight was a significant factor in serum progesterone level at the time of the pregnancy test, with nearly 30% of patients weighing ≥90.7 kg having serum progesterone level of <15 ng/mL, a value associated with lower LBRs in prior studies. However, we found no effect of low progesterone levels on LBR after cryopreserved embryo transfer cycles in a clinic where progesterone dosing was increased if serum progesterone levels were <15 ng/mL.

Effect of body mass index on intrauterine insemination cycle success.

OBJECTIVE: To determine whether body mass index (BMI) affects intrauterine insemination treatment success. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): A total of 3,217 intrauterine insemination treatment cycles in 1,306 patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome was live birth rate stratified by BMI. Secondary outcomes included rates of clinical pregnancy (defined as an intrauterine pregnancy with a heartbeat present on ultrasound), multiple gestation, biochemical pregnancy, missed abortion, ectopic, and spontaneous abortion. RESULT(S): Women with BMI 25 to 29.99 kg/m2 or ≥30 kg/m2 were equally likely to have a live birth as women of normal BMI. Women with BMI ≥30 kg/m2 did have a higher likelihood of biochemical pregnancy than women with normal BMI. CONCLUSION(S): A BMI between 25 and 29.99 kg/m2 or ≥30 kg/m2 does not appear to have a negative effect on live birth after intrauterine insemination. Obesity may be associated with a higher risk of biochemical pregnancy after intrauterine insemination.

Laparoscopic resection of functional, noncommunicating uterine horn in close approximation to functional hemiuterus.

OBJECTIVE: To review the presentation of unicornuate uterus with a functional noncommunicating rudimentary uterine horn and a laparoscopic method of management, highlighting laparoscopic surgical techniques. DESIGN: A video review of unicornuate uterus with a functional noncommunicating rudimentary uterine horn and a laparoscopic approach to treatment in a 13-year-old pubertal female with severe menstrual pain. SETTING: Tertiary care facility. PATIENT(S): A 13-year-old G0 was referred to the clinic for severe cyclic right lower quadrant pain during menses. Transvaginal ultrasonography revealed a left unicornuate uterus with a right-sided noncommunicating rudimentary horn measuring 4.8 × 4.7 × 4.6 cm, containing blood consistent with hematometra. Her kidneys were bilaterally present and normal by ultrasonography. INTERVENTION(S): Because of the patient's worsening pain and the presence of hematometra, we proceeded with diagnostic laparoscopy and removal of the rudimentary uterine horn. The entire procedure was performed laparoscopically, with an estimated total blood loss of 20 mL. Included are tips for laparoscopic resection and suturing. MAIN OUTCOME MEASURE(S): Pathologic features and postoperative course. RESULTS: The patient's pathologic features were benign, and her severe menstrual pain was resolved. She had no complications or readmissions. CONCLUSION(S): In patients with severe menstrual pain from outflow obstruction from a noncommunicating rudimentary uterine horn with functional endometrium, laparoscopic resection can be a safe and effective method of treatment.

A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). DESIGN: Open-label randomized controlled trial. SETTING: Academic medical center using two clinic sites. PATIENT(S): Women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility. INTERVENTIONS(S): Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for one treatment cycle. MAIN OUTCOME MEASURE(S): Ovulation defined as mid-luteal serum progesterone concentration ≥3 ng/mL. RESULT(S): Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups. CONCLUSION(S): The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate. CLINICAL TRIAL REGISTRATION NUMBER: NCT02802865.

Effect of body weight on early hormone levels in singleton pregnancies resulting in delivery after in vitro fertilization.

OBJECTIVE: To evaluate which clinical characteristics influence early maternal ß-human chorionic gonadotropin (hCG) and progesterone levels in in vitro fertilization (IVF) pregnancies. DESIGN: Retrospective cohort analysis. SETTING: Academic medical center. PATIENT(S): Women with a live birth after single-blastocyst embryo transfer in either a fresh or frozen cycle between 2004 and 2017, comprising 1,282 pregnancies in 1,057 patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The initial human chorionic gonadotropin concentration (ß-hCG1) measured a mean of 10 days (range: 9-12 days) after embryo transfer, the rate of increase in ß-hCG concentrations, and progesterone concentration, with all analyses controlled for number of days between the embryo transfer and the ß-hCG1 measurement. RESULT(S): The clinical factor that positively influenced the ß-hCG1 level in the fresh cycle was the stimulation type (antagonist cycle higher than long agonist cycle). The clinical factors that negatively influenced both fresh and frozen cycle ß-hCG1 were lower embryo quality and increasing body weight. Increasing weight negatively impacted progesterone levels in both fresh and frozen cycles. A 100 lb (45.4 kg) difference in weight was associated with a 34.8% reduction in ß-hCG1 for both fresh and frozen cycle pregnancies. The rate of increase in ß-hCG was unaffected by body weight. A 100 lb (45.4 kg) difference in weight was associated with a 53.3% and a 32.8% reduction in progesterone in fresh and frozen cycles, respectively. CONCLUSION(S): Increasing body weight is associated with significantly lower ß-hCG and progesterone concentrations in early pregnancy after blastocyst single-embryo transfer in both fresh and frozen cycles. Clinicians should consider this when evaluating these hormone levels for prognostic and diagnostic purposes.

Ethical issues identified by obstetrics and gynecology learners through a novel ethics curriculum.

OBJECTIVE: Obstetrics and gynecology (ob/gyn) is fraught with bioethical issues, the professional significance of which may vary based on clinical experience. Our objective was to utilize our novel ethics curriculum to identify ethics and professionalism issues highlighted by ob/gyn learners and to compare responses between learner levels to further inform curricular development. STUDY DESIGN: We introduced an integrated and dynamic ob/gyn ethics and professionalism curriculum and mixed methods analysis of 181 resulting written reflections (case observation and assessments) from third-year medical students and from first- to fourth-year ob/gyn residents. Content was compared by learner level using basic thematic analysis and summary statistics. RESULTS: Within the 7 major ethics and professionalism domains, learners wrote most frequently about miscellaneous ob/gyn issues such as periviability and abortion (22% of students, 20% of residents) and problematic treatment decisions (20% of students, 19% of residents) rather than professional duty, communication, justice, student-/resident-specific issues, or quality of care. The most commonly discussed ob/gyn area by both learner groups was obstetrics rather than gynecology, gynecologic oncology, or reproductive endocrinology and infertility, although residents were more likely to discuss obstetrics-related concerns than students (65% vs 48%; P = .04) and students wrote about gynecologic oncology-related concerns more frequently than residents (25% vs 6%; P = .002). In their reflections, sources of ethical value (eg, the 4 classic ethics principles, professional guidelines, and consequentialism) were cited more frequently and in greater number by students than by residents (82% of students cited at least 1 source of ethical value vs 65% of residents; P = .01). Residents disagreed more frequently with the ethical propriety of clinical management than did students (67% vs 43%; P = .005). CONCLUSION: Our study introduces an innovative and dynamic approach to an ob/gyn ethics and professionalism curriculum that highlights important learner-identified ethics and professionalism issues both specific to ob/gyn and common to clinical medicine. Findings will help ob/gyn educators best utilize and refine this flexible curriculum such that it is appropriately focused on topics relevant to each learner level.

Effect of surgery for endometrioma on ovarian function.

Endometriosis affects a significant proportion of reproductive-aged women. The impact of the disease on ovarian function is an important consideration when planning treatment in women who want to retain the potential of future childbearing. This review will specifically address the association between endometriomas and diminished ovarian reserve, with a particular focus on the impact of surgical endometrioma resection on ovarian function. The existing literature supports an adverse effect of ovarian endometriomas on spontaneous ovulation rates, markers of ovarian reserve, and response to ovarian stimulation, although data on clinical pregnancy and live birth rates remain inconsistent. Surgical removal of endometriomas may worsen ovarian function by removing healthy ovarian cortex or compromising blood flow to the ovary. It is evident that surgical excision of endometriomas acutely impairs ovarian function as measured by ovarian reserve markers; whether this represents progressive or long term impairment remains the subject of ongoing investigation.