ART outcomes in lean compared to obese phenotypes of polycystic ovarian syndrome.

RESEARCH QUESTION: To investigate differences in reproductive outcomes among IVF patients with lean compared to obese polycystic ovarian syndrome (PCOS) phenotypes. DESIGN: A retrospective cohort study of patients with PCOS who underwent IVF in a single, academically affiliated infertility center in the USA between December 2014 and July 2020. The diagnosis of PCOS was assigned based on Rotterdam criteria. Patients were designated as lean (< 25) or overweight/obese (≥ 25) PCOS phenotype based on BMI (kg/m2) at cycle start. Baseline clinical and endocrinologic laboratory panel, cycle characteristics, and reproductive outcomes were analyzed. The cumulative live birth rate included up to 6 consecutives cycles. A Cox proportional hazards model and Kaplan-Meier curve for estimating live birth rates were used to compare the two phenotypes. RESULTS: A total of 1395 patients who underwent 2348 IVF cycles were included. The mean (SD) BMI was 22.7 (2.4) in the lean and 33.8 (6.0) in the obese group (p < 0.001). A number of endocrinological parameters were similar between lean and obese phenotypes: total testosterone 30.8 ng/dl (19.5) vs 34.1 (21.9), p > 0.02 and pre-cycle hemoglobin A1C 5.33% (0.38) vs 5.51% (0.51) p > 0.001, respectively. The CLBR was higher in those with a lean PCOS phenotype: 61.7% (373/604) vs 54.0% (764/1414) respectively. Miscarriage rates were significantly higher for O-PCOS patients (19.7% (214/1084) vs 14.5% (82/563) p < 0.001) and the rate of aneuploids was similar (43.5%, 43.8%, p = 0.8). A Kaplan-Meier curve estimating the proportion of patients with a live birth was higher in the lean group (log-rank test p = 0.013). After adjusting for potential confounders, the lean phenotype was associated with an increased hazard ratio for live birth: HR = 1.38 p < 0.001. CONCLUSIONS: Lean PCOS phenotype is associated with a significantly higher CLBR compared to their obese counterparts. Miscarriage rates were significantly higher among obese patients, despite comparable pre-cycle HBA1C and similar aneuploidy rates in patients who underwent PGT-A.

Fertility Preservation in Endometriosis: Does Patient Symptomatology Affect the Extent of the Ovarian Response?

This study is to identify factors and patient symptomatology affecting ovarian response in women with endometriosis who seek fertility preservation. An observational cross-sectional study was conducted from July 2017 to May 2020 at a tertiary university-affiliated medical center. We included patients who were treated in the endometriosis clinic and underwent fertility preservation. Patients completed an online questionnaire that was cross-referenced with electronic charts. An analysis related to patient data and fertility preservation cycles and a mediation analysis were performed. The mean patient age at time of fertility preservation was 35.2 (± 4.9) years. The mean accumulated number of oocytes vitrified per patient was 16.7 (± 12.1) oocytes. The correlation coefficient assessed between the number of oocytes vitrified per cycle and AMH was significantly positive at +0.472, p = 0.006. The examined reported symptoms were lethargy, chronic pelvic pain, dyschezia, dyspareunia, bowel-associated symptoms, and urinary tract symptoms. The number of oocytes vitrified correlated with the number of reported symptoms and clinical characteristics at - 0.497, p = 0.0001, and - 0.442, p = 0.0001, respectively. In a mediation analysis, the potential causality of surgical intervention in the relationship between the number of symptoms and ovarian response was - 0.300 (95% CI [0.15, 1.905], p = 0.05), and the calculated proportion of mediation was estimated to be 17%. We observed a significant negative association between the number of clinical symptoms and the quantity of vitrified oocytes. This relationship was only partly associated with prior surgical intervention. AMH was found to have the highest correlation with treatment success in patients with endometriosis undergoing fertility preservation.

Female Genital Tuberculosis.

Female genital tuberculosis (FGTB) is an important cause of morbidity and infertility worldwide. Mycobacterium tuberculosis most commonly spreads to the genital tract from a focus elsewhere in the body and affects the bilateral fallopian tubes and/or endometrium. Many patients with FGTB have indolent disease and are only diagnosed after evaluation for infertility. Women may present with menstrual irregularities, lower abdominal or pelvic pain, or abnormal vaginal discharge. Given the low sensitivity of diagnostic tests, various composite reference standards are used to diagnose FGTB, including some combination of endoscopic findings, microbiological or molecular testing, and histopathological evidence in gynecological specimens. Early treatment with a standard regimen of a 2-month intensive phase with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by a 4-month continuation phase with isoniazid and rifampin, is recommended to prevent irreversible organ damage. However, even with treatment, FGTB can lead to infertility or pregnancy-related complications, and stigma is pervasive.

Endometrial compaction does not predict live birth in single euploid frozen embryo transfers: a prospective study.

STUDY QUESTION: Is there a relationship between endometrial compaction and live birth in euploid frozen embryo transfer (FET) cycles? SUMMARY ANSWER: Live birth rates (LBRs) were similar in both patients that demonstrated endometrial compaction or no compaction in single euploid FETs. WHAT IS KNOWN ALREADY: There has been increasing interest in the correlation between endometrial compaction and clinical outcomes but there has been conflicting evidence from prior investigations. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study from 1 September 2020 to 9 April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed at a single, academically affiliated fertility center in which patients who had an autologous single euploid FET using a programmed or modified natural cycle protocol were included. All embryos had trophectoderm biopsy for preimplantation genetic testing for aneuploidy followed by vitrification at the blastocyst stage. Two ultrasound measurements of endometrial thickness (EMT) were obtained. The first measurement (T1) was measured transvaginally within 1 day of initiation of progesterone or ovulation trigger injection, and a second EMT (T2) was measured transabdominally at the time of embryo transfer (ET). The primary outcome (LBR) was based on the presence and proportion of compaction (percentage difference in EMT between T1 and T2). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 186 participants included, 54%, 45%, 35%, 28% and 21% of women exhibited >0%, ≥5%, ≥10%, ≥15% and ≥20% endometrial compaction, respectively. Endometrial compaction was not predictive of live birth at any of the defined cutoffs. A sub-analysis stratified by FET protocol type (n = 89 programmed; n = 97 modified natural) showed similar results. LIMITATIONS, REASONS FOR CAUTION: There was the potential for measurement error in the recorded EMTs. The T2 measurement was performed transabdominally, which may cause potential measurement error, as it is generally accepted that transvaginal measurements of EMT are more accurate, though, any bias is expected to be non-differential. The sub-analysis performed looking at FET protocol type was underpowered and should be interpreted with caution. Our study, however, represents a pragmatic approach, as it allowed patients to avoid having to come in for an extra transvaginal ultrasound the day before or on the day of ET. WIDER IMPLICATIONS OF THE FINDINGS: Assessing endometrial compaction may lead to unnecessary cycle cancellation. However, further studies are needed to determine if routine screening for endometrial compaction would improve clinical outcomes. STUDY FUNDING/COMPETING INTEREST(S): No authors report conflicts of interest or disclosures. There was no study funding. TRIAL REGISTRATION NUMBER: NCT04330066.

Clinical outcomes and utilization from over a decade of planned oocyte cryopreservation.

RESEARCH QUESTION: What is the clinical experience of patients who have undergone planned oocyte cryopreservation and oocyte thawing and warming? DESIGN: Retrospective observational cohort study. All women who completed planned oocyte cryopreservation at a single large university-affiliated fertility centre between June 2006 and October 2020 were identified, including the subset who returned to use their oocytes. Patients who underwent oocyte cryopreservation for medical reasons were excluded. Baseline demographics, oocyte cryopreservation and thawing-warming cycle parameters, and clinical outcomes, were extracted from the electronic medical record. The primary outcome was cumulative live birth rate (LBR), and secondary outcomes were cumulative clinical pregnancy rate (CPR), and CPR and LBR per transfer. Results were stratified by age at time of cryopreservation (<38 and ≥38 years). RESULTS: Of 921 patients who underwent planned oocyte cryopreservation, 68 (7.4%) returned to use their oocytes. Forty-six patients (67.6%) completed at least one embryo transfer. The CPR per transfer was 47.5% and LBR was 39.3%. The cumulative LBR per patient who initiated thawing-warming was 32.4%. Cycle outcomes were not significantly different in patients aged younger than 38 years and those aged 38 years or over. No patient aged 40 years or older (n = 6) was successful with their cryopreserved oocytes. Ten patients (14.7%) who were unsuccessful with their cryopreserved oocytes achieved a live birth using donor oocytes, with most (7/10) of these patients aged 38 years and older. CONCLUSION: Only a small percentage of patients returned to use their oocytes, and 32% of those were able to achieve a live birth.

Routine ketorolac at oocyte retrieval decreases postoperative narcotic use by more than 50.

OBJECTIVE: To study the impact of routine ketorolac administration during oocyte retrieval on the proportion of patients who require postoperative narcotics for analgesia. DESIGN: Retrospective cohort study. SETTING: Single, university-affiliated infertility clinic. PATIENTS: All women undergoing oocyte retrieval between July and November 2016 (non-ketorolac group [NKG]; n = 826) and April-August 2017 (ketorolac group, KG; n = 1780). INTERVENTIONS: A single 30 mg intravenous dose of ketorolac was administered after the oocyte retrieval procedure. MAIN OUTCOME MEASURES: The number of patients who required postoperative narcotic analgesia, postoperative complication rate, and fresh embryo transfer pregnancy outcomes were examined. RESULTS: In the KG, we found a significant decrease in the patients who required narcotics after oocyte retrieval compared with the NKG (12% KG vs. 25.5% NKG). We found no significant change in the clinical pregnancy rate (CPR) resulting from fresh embryo transfer after our intervention (NKG CPR 32.6%, KG CPR 32.4%). Furthermore, there was no increase in postoperative bleeding complications in the KG. CONCLUSIONS: Routine use of ketorolac at the time of oocyte retrieval may decrease the rate of postoperative opioid use without adversely impacting pregnancy and complication rates.

Navigating the Challenges of Fertility and Reproductive Planning for Terminal Cancer Patients.

Among the many disruptive effects of a terminal cancer diagnosis in young people is its ability to affect reproductive planning and the opportunity for parenthood. While many reproductive-aged cancer patients receive fertility counseling at diagnosis, ongoing guidance often does not occur during the illness course and associated distress may go unrecognized. Using a case-based framework, this palliative care rounds explores the existential, spiritual, ethical, and logistical challenges that complicate reproductive planning for patients and families as they face a terminal cancer diagnosis. We advocate that palliative care providers should seize currently underrecognized opportunities to screen for distress associated with fertility and reproduction at end of life and utilize an interdisciplinary team approach to provide appropriate support and counseling throughout the illness and bereavement experience.

Vaginal cuff dehiscence following transvaginal oocyte retrieval: a case report.

BACKGROUND: Vaginal cuff dehiscence (VCD) is a rare but potentially serious complication following hysterectomy with an estimated incidence of 0.14-1.4%. There is a wide range of risk factors thought to contribute to VCD, but due to its rare occurrence, much still remains to be learned about the true impact of risk factors leading to dehiscence. We present here the second known report of VCD to occur in a patient undergoing transvaginal oocyte retrieval during her fertility treatment. This case highlights what may become a more common clinical scenario as more premenopausal women are diagnosed with reproductive tract cancers and access assisted reproductive therapies to preserve fertility. CASE PRESENTATION: Our patient is a 35-year-old G1 P0 A1 who had undergone ovary-sparing total laparoscopic hysterectomy (TLH) following diagnosis of endometrial adenocarcinoma. She underwent two in-vitro fertilization (IVF) cycles after TLH to bank frozen blastocysts, the first vaginal oocyte retrieval (VOR) taking place 12 weeks following hysterectomy. She experienced VCD during her second VOR that occurred 17 weeks after TLH, the second case of VCD to be reported in the literature during fertility preservation treatment following hysterectomy. The patient underwent an emergent and uncomplicated repair of the defect vaginally the same day. CONCLUSIONS: Currently there are no guidelines in place for women who have undergone hysterectomy with regard to when they can begin fertility treatment in the post-operative period. Based on now two case reports, it is worth considering extension of the typical 6-week timeline of avoidance of vaginal procedures to allow for full cuff healing. Infertility providers should also be mindful of limiting transvaginal ultrasounds where possible to reduce force along the cuff.

A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T).

OBJECTIVE: To determine the optimal infertility therapy for women at the end of their reproductive potential. DESIGN: Randomized clinical trial. SETTING: Academic medical centers and private infertility center in a state with mandated insurance coverage. PATIENT(S): Couples with ≥ 6 months of unexplained infertility; female partner aged 38-42 years. INTERVENTION(S): Randomized to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant. MAIN OUTCOME MEASURE(S): Proportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after two treatment cycles and at the end of treatment. RESULT(S): We randomized 154 couples to receive CC/IUI (N = 51), FSH/IUI (N = 52), or immediate IVF (N = 51); 140 (90.9%) couples initiated treatment. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles. CONCLUSION(S): A randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group. CLINICAL TRIAL REGISTRATION NUMBER: NCT00246506.

The effect of body mass index on the outcomes of first assisted reproductive technology cycles.

OBJECTIVE: To provide assisted reproductive technology (ART) outcome rates per body mass index (BMI) category after controlling for potential confounders. DESIGN: Retrospective cohort study. SETTING: Large university-affiliated infertility practice. PATIENT(S): Women undergoing ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live birth. Analyses were stratified according to BMI category and adjusted for potential confounders, including maternal and paternal age, baseline serum FSH, duration of gonadotropin stimulation, mean daily gonadotropin dose, peak serum E(2), number of oocytes retrieved, use of intracytoplasmic sperm injection, embryo quality and number, transfer day, and number of embryos transferred. RESULT(S): We analyzed the first autologous fresh IVF or IVF-ICSI cycle of 4,609 patients. There were no differences in the rates of cycle cancellation, spontaneous abortion, biochemical and ectopic pregnancies, or multiple births. After adjusting for potential confounders, patients with BMI ≥ 30.0 kg/m(2) had significantly decreased odds of implantation, clinical pregnancy, and live birth. The adjusted odds ratio (95% confidence interval [CI]) of live birth were 0.63 (0.47-0.85) for BMI 30.00-34.99, 0.39 (0.25-0.61) for BMI 35.00-39.99, and 0.32 (0.16-0.64) for BMI ≥ 40.0 compared with normal-weight cohorts. CONCLUSION(S): Obesity has a significant negative effect on ART outcomes. Patients with BMI > 30 kg/m(2) have up to 68% lower odds of having a live birth following their first ART cycle compared with women with BMI < 30.

Management of a cervical heterotopic pregnancy presenting with first-trimester bleeding: case report and review of the literature.

OBJECTIVE: To report a rare case of a cervical heterotopic pregnancy resulting from intrauterine insemination (IUI) that presented with first-trimester bleeding. DESIGN: Case report and literature review. SETTING: Large university-affiliated infertility practice. PATIENT(S): A 40-year-old gravida 2 para 1 Asian woman at 7-3/7 weeks gestational age following clomiphene citrate/IUI for the treatment of secondary infertility presented with heavy vaginal bleeding for several days. INTERVENTION(S): Transvaginal ultrasound on admission revealed a single live intrauterine pregnancy and a cervical gestational sac containing a nonviable embryo. The patient continued to have vaginal bleeding and 2 days later underwent removal of the cervical ectopic pregnancy tissue with ring forceps, as well as an ultrasound-guided intracervical Foley balloon and cerclage placement. The bleeding subsided, and 48 hours later the Foley and cerclage were removed. MAIN OUTCOME MEASURE(S): Pregnancy outcome. RESULT(S): The remainder of the pregnancy was uncomplicated and the patient had a full-term cesarean delivery for footling breech of a healthy male infant. CONCLUSION(S): Cervical heterotopic pregnancy is a very rare event that almost universally results from infertility treatment. We present a case where we were able to remove the cervical ectopic and tamponade the bleeding, thus preserving the intrauterine pregnancy for this subfertile couple, and we review the existing literature.

Fertility preservation: nonsurgical and surgical options.

Improved surveillance and treatment regimens have resulted in decreased mortality rates among cancer patients, allowing these women to focus on survival and quality of life, including the ability to preserve their fertility. The treatments that have improved survival among both adults and children diagnosed with cancer are often gonadotoxic, especially those that employ high doses of alkylating agents and radiation therapy directed near or toward the pelvis. The impact on the ovarian reserve is related to the accelerated depletion of the primordial germ cell pool resulting from these therapies. Nonsurgical approaches to fertility preservation, including embryo cryopreservation from in vitro fertilization, oocyte cryopreservation from controlled ovarian hyperstimulation, and in vitro maturation of oocytes, are discussed. Surgical approaches such as conservative gynecologic surgery, ovarian transposition, and ovarian tissue cryopreservation are reviewed. Guidelines from the American Society for Reproductive Medicine and the American Society of Clinical Oncology classify these treatments into established and experimental procedures, and they provide the practitioner with an optimal approach to preserve the fertility of these patients before the initiation of their cancer therapies.

Pregnancy loss in the first in vitro fertilization cycle is not predictive of subsequent delivery in women over 40 years.

OBJECTIVE: To determine if there is an association between first IVF cycle outcome and subsequent delivery rate for women over 40 years. DESIGN: Retrospective data analysis. SETTING: Large, private academically affiliated IVF center. INTERVENTION(S): Patients over 40 years of age undergoing IVF. MAIN OUTCOME MEASURE(S): Delivery rate compared between patients with a pregnancy loss versus a negative beta-hCG in their first cycle. Additional factors including subsequent pregnancy losses, total number of IVF cycles, and delivery rates per cycle were also analyzed. RESULT(S): Among women who underwent their first IVF cycle over age 40, 8% of women had a pregnancy loss and 82% had a negative beta-hCG in their initial IVF cycle. In the pregnancy loss and negative beta-hCG groups, 17.9% and 21.9%, respectively, had a successful delivery in a future cycle. There were no further pregnancies leading to delivery after the fourth treatment cycle for the pregnancy loss group and the sixth treatment cycle for the negative beta-hCG group. The average number of cycles and the number of subsequent pregnancy losses were similar in both groups. CONCLUSION(S): Outcome of initial IVF cycle is not prognostic of future delivery for women over the age of 40 years.

One last chance for pregnancy: a review of 2,705 in vitro fertilization cycles initiated in women age 40 years and above.

OBJECTIVE: To describe live birth rates and predictors of success in 1-year age increments for women > or =40 years when initiating assisted reproductive technologies (ART). DESIGN: Retrospective database analysis. SETTING: A large university-affiliated infertility center. PATIENT(S): One thousand two hundred sixty-three women undergoing 2,705 ART cycles at age 40 or above. INTERVENTION(S): Couples undergoing ART. MAIN OUTCOME MEASURE(S): Pregnancy and live birth rates per cycle start were determined based on 1-year increments in women aged > or =40. Predictors of success, including number of embryos transferred, number of fetal heartbeats, availability of embryos for cryopreservation, and cycle day 3 FSH levels, were analyzed. RESULT(S): The overall live birth rate per cycle start was 9.7%. Cumulative live birth rates in women ranged from 28.4% if starting ART at age 40 to 0 by age 46. The overall spontaneous abortion rate was 32.6% (range, 23.9%-66.7%). Higher pregnancy rates were predicted by the greater number of embryos available for transfer, by the availability of excess embryos for cryopreservation, and by the presence of two fetal heartbeats on ultrasound. The outcome of the first IVF cycle did not predict the outcome of subsequent cycles. CONCLUSION(S): Assisted reproductive technology has a reasonable chance for success (>5%) up until the end of the forty-third year. Twins on initial ultrasound, large numbers of embryos available for transfer, and the presence of excess embryos for cryopreservation predict higher live birth rates.

Characterization and mutation analysis of the human formin-2 (FMN2) gene in women with unexplained infertility.

OBJECTIVE: Formin-2 (Fmn2) mutant mice produce oocytes with meiosis I arrest. Our aim was to describe the human FORMIN-2 (FMN2) gene and to identify DNA sequence polymorphisms in patients with unexplained infertility and multiple failed IVF cycles. DESIGN: Institutional review board-approved observational case-control study. SETTING: Infertility center and university hospital. PATIENT(S): Sixty-two fertile controls and seven subjects with unexplained infertility. INTERVENTION(S): BLASTP (www.ncbi.nlm.nih.gov) was used to map the genomic DNA and complementary DNA sequence of FMN2. Genomic DNA was extracted from blood leukocyte samples. The polymerase chain reaction was used to amplify FMN2 gene exons for analysis by denaturing gradient gel electrophoresis. MAIN OUTCOME MEASURE(S): Characterization of the FMN2 gene and identification of fragment melting polymorphisms (FMPs). RESULT(S): FMN2 includes 411,960 base pairs (bp) of DNA with 6,204 bp in 18 exons. There was no difference in FMN2 FMP allele frequencies between the controls and subjects. One patient was homozygous for one FMP. CONCLUSION(S): The human FMN2 gene is conserved between evolutionarily diverse vertebrates. It is likely that FMN2 has the same function as Fmn2 in the mouse (i.e., maintenance of the meiotic spindle). Prospective identification of patients with meiosis I arrest is necessary to determine whether FMN2 mutations are a cause of unexplained infertility.

A mesothelial cyst of the round ligament presenting as an inguinal hernia after gonadotropin stimulation for in vitro fertilization.

OBJECTIVE: To report the case of a round ligament cyst which, as the result of gonadotropin stimulation for IVF, simulated an incarcerated inguinal hernia. DESIGN: Case report. SETTING: A private infertility center and a university hospital. PATIENT(S): A 31-year-old woman who developed left lower quadrant pain after gonadotropin stimulation for IUI and a tender left inguinal mass after increasing ovarian stimulation for IVF/intracytoplasmic sperm injection. INTERVENTION(S): Surgical excision of a mesothelial cyst of the left round ligament and exploration of the left inguinal canal. MAIN OUTCOME MEASURE(S): Successful surgical excision of left inguinal mass. RESULT(S): Resolution of symptoms. CONCLUSION(S): Mesothelial cysts of the round ligament should be included in the differential diagnosis of inguinal masses in women. Gonadotropin stimulation might cause previously unrecognized cysts to simulate an incarcerated inguinal hernia, necessitating surgical repair.