Anti-Müllerian hormone and embryo quality as determined by time-lapse imaging.

BACKGROUND: There is conflicting evidence as to whether serum anti-Mullerian hormone (AMH) is a biomarker of oocyte quality in addition to its known role in assessing ovarian reserve. This study aims to examine the relationship between AMH and embryo potential as assessed by time-lapse imaging (TLI). METHODS: A total of 106 embryos from 67 patients were included in the study. All subjects were women with recorded pre-treatment AMH levels who underwent in vitro fertilization using a TLI embryo incubator. Exclusion criteria included cases of donor oocytes, rescue-ICSI, and >2 embryos transferred. Individual time measures, presence of multinucleation (MN), and composite TLI score were analyzed in relation to patient AMH. Linear regression was used to model AMH among embryo TLI parameters while controlling for age as a continuous covariate. RESULTS: There was no statistically significant difference in the mean AMH levels between patients in the normal and abnormal time frames for CC2, S2, and T5. Similarly, there was no significant difference in AMH levels based on composite TLI score or presence/absence of multinucleation. The lack of association between AMH levels and embryo TLI variables persisted after controlling for age (Grade P=0.19, CC2 P=0.47, S2 P=0.52, t5 P=0.34, MN P=0.92). CONCLUSIONS: Serum AMH is not predictive of embryo quality as assessed by TLI standardized time intervals, composite score, and presence of MN. From a clinical perspective, these findings suggest that diminished ovarian reserve alone does not imply poorer quality of individual embryos.

Fertility preservation in a transgender man without prolonged discontinuation of testosterone: a case report and literature review.

OBJECTIVE: To study the feasibility of fertility preservation in a transgender man without an extended period of androgen cessation. DESIGN: Report of a foundational case of oocyte cryopreservation in a transgender man without stopping testosterone therapy before controlled ovarian stimulation. We performed a literature review, identifying five publications on oocyte cryopreservation outcomes in transgender men on testosterone. SETTING: A university-affiliated fertility clinic in Canada. PATIENTS: A 28-year-old transgender man taking testosterone for 3 years requesting oocyte cryopreservation before gender-affirming surgery. He desired to proceed without stopping testosterone. Pretreatment antimüllerian hormone level was 1.89 ng/mL. The patient's consent was obtained for written publication. INTERVENTIONS: Testosterone was stopped for only three doses (immediately before and during ovarian stimulation). A standard antagonist protocol was used with letrozole to minimize estrogenic side effects. MAIN OUTCOME MEASURES: Number of oocytes retrieved and days off testosterone. RESULTS: Thirteen oocytes were retrieved; 11 were mature and vitrified. The total time off testosterone was 24 days. In all prior publications, testosterone was stopped for 3-6 months. CONCLUSIONS: Transgender men have traditionally discontinued exogenous testosterone until the resumption of menses (≤6 months). This is known to be distressing. This is the first published case demonstrating the feasibility of ovarian stimulation without prolonged testosterone cessation in a transgender man. Future studies with a larger sample size should be performed to confirm these findings. The short duration off testosterone may improve patient's experiences, increase treatment acceptability, and decrease gender dysphoria for transgender men considering fertility preservation.

Measurement of Luteinizing Hormone Level After Gonadotropin-Releasing Hormone Agonist Trigger Is Not Useful for Predicting Oocyte Maturity.

OBJECTIVE: To study whether the measurement of LH after GnRH agonist trigger is correlated with the proportion of mature oocytes. METHODS: We performed a retrospective cohort study at a private, university-affiliated fertility centre in Vancouver, BC. Patients who underwent IVF/ICSI cycles and used a GnRH agonist trigger were included. Serum LH levels were measured on the day of trigger and one day later. The main study outcome measure was the proportion of mature oocytes. RESULTS: Including all 97 cycles in the cohort, the average post-trigger LH level was 69.3 IU/L (10.5-133.3 IU/L) and the average rise was 66.8 IU/L (10.0-129.4 IU/L). The mean number of oocytes collected was 17 and, on average, 82% were mature. We did not find any association between post-trigger LH levels (r = 0.004, P = 0.968) or rise in LH level (r = 0.01, P = 0.92) and the proportion of mature oocytes collected. The percentage rise in LH level was also not predictive of the proportion of mature oocytes in the estradiol and oral contraceptive pill groups separately (estradiol r = 0.118, OCP r = 0.07; P > 0.05) or together (r = 0.1, P = 0.34). CONCLUSION: Neither the absolute post-trigger LH level nor the rise in LH level is predictive of the proportion of mature oocytes collected. Taken together with the excellent response to GnRH agonist trigger evidenced by the average oocyte maturity, we do not believe it is necessary to measure post-trigger LH levels.

Case report: an identical twin with Sertoli-Leydig cell tumor.

Our report details the workup and management of a 43-year-old woman with an identical twin who presented with 2 years of virilization and secondary amenorrhea. Serum total testosterone was elevated. An MRI did not identify adnexal or adrenal pathology. Subsequent ovarian vein sampling demonstrated unilateral testosterone elevation. The patient underwent laparoscopic unilateral oophorectomy resulting in the diagnosis of Sertoli-Leydig cell tumor (SLCT). Although SLCT is a rare sex-cord ovarian tumor, it is associated with endometrial hyperplasia and malignancy. Our goals are to review the workup of androgen-secreting tumors and discuss the clinical importance of the DICER1 mutation in the context of SLCT. In this case, an identical twin underwent DICER1 testing which was one of the essential steps in her clinical management.

Adverse perinatal outcomes associated with crown-rump length discrepancy in in vitro fertilization pregnancies.

OBJECTIVE(S): To determine whether an association exists between small crown-rump length (CRL) and adverse obstetrical outcomes in pregnancies conceived by IVF and to compare a CRL reference based on IVF pregnancies to a reference based on spontaneous pregnancies. DESIGN: Retrospective cohort study. CRL was classified as small by comparing it with the local university hospital maternal fetal medicine standard and the Monash IVF reference chart. SETTING: University-affiliated fertility center. PATIENT(S): Singleton pregnancies conceived by IVF with ultrasounds performed between 7+0 and 8+6 weeks of gestational age. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy loss, preterm birth, and low birth weight. RESULT(S): Included were 940 clinical pregnancies. The overall and CRL-discrepant miscarriage rates were 12.7% and 41%, respectively. When CRL was small, the maternal age-adjusted odds of miscarriage were 13.8 times higher (95% confidence interval [CI], 8.9-21.6). At age 30, small CRL was associated with a 30% risk of miscarriage, versus 61% at age 45. There was no association between small CRL and preterm birth or low birth weight. The sensitivity and specificity for predicting miscarriage from the optimal Monash cut point were 0.69 (95% CI, 0.61-0.77) and 0.84 (95% CI, 0.82-0.87), which were similar to those of the CRL reference based on spontaneous pregnancies. CONCLUSION(S): Small CRL in IVF pregnancy was strongly associated with miscarriage, especially in the context of advanced maternal age. Small CRL was not associated with preterm birth or low birth weight. A CRL reference based on IVF pregnancies was equivalent to the standard reference for predicting miscarriage.

Peak Serum Estradiol Level During Controlled Ovarian Stimulation Is not Associated with Lower Levels of Pregnancy-Associated Plasma Protein-A or Small for Gestational Age Infants: A Cohort Study.

OBJECTIVE: During controlled ovarian stimulation in IVF, supraphysiologic levels of estradiol (E2) have been associated with poor placentation and adverse pregnancy outcomes. This study aimed to investigate whether high peak E2 on the day of human chorionic gonadotropin trigger is associated with low pregnancy-associated plasma protein-A (PAPP-A) and adverse perinatal outcomes. METHODS: We performed a retrospective cohort study at a private, university-affiliated fertility centre in Vancouver, BC. We enrolled 216 patients with a singleton pregnancy after fresh embryo transfer who also underwent first trimester screening. Adverse perinatal outcomes were collected from a local registry and included preterm birth, hypertension in pregnancy, antepartum hemorrhage, intrauterine growth restriction, SGA, stillbirth, admission to the NICU, and neonatal death. RESULTS: High serum E2 (≥13 035 pmol/L) at controlled ovarian stimulation was not correlated with low PAPP-A (<0.4 multiples of the median) at first trimester screening (P = 0.46). When each adverse outcome was analysed separately, there was no association between high E2 and any of the outcomes (P > 0.05 for all). High peak E2 was not associated with a total composite of maternal and neonatal adverse birth outcomes (P = 0.30). CONCLUSION: Our results do not support the theory that high E2 at fresh embryo transfer impedes placentation. We found no association between peak E2 and low PAPP-A levels or adverse pregnancy outcomes.

Longer ovarian stimulation reduces embryo number and clinical pregnancy rate in long GnRH agonist cycles.

BACKGROUND: The aim of this study was to analyze whether the length of controlled ovarian stimulation affects in vitro fertilization (IVF) cycle outcomes. METHODS: This retrospective cohort study was performed at a private, university-affiliated fertility centre. We reviewed 1522 IVF cycles, comprising 979 long gonadotropin-releasing hormone (GnRH) agonist and 543 GnRH antagonist protocols. All subjects underwent controlled ovarian stimulation followed by fresh embryo transfer. Logistic regression analysis was used to examine the relationship between trigger day and the following cycle outcomes: normal fertilization rate (FR), proportion of mature oocytes, proportion of cycles with embryos for cryopreservation, and clinical pregnancy rate (CPR). RESULTS: In long agonist cycles, having more days of stimulation was associated with a lower clinical pregnancy rate (OR=0.87, 95% CI=0.80-0.96, P=0.01). Longer stimulation also resulted in fewer cycles with supernumerary embryos for cryopreservation (OR=0.84, 95% CI=0.77-0.92, P=0.0005), despite a having greater number of mature oocytes retreived (OR=1.05, 95% CI=1.01-1.10, P=0.04). For each additional day of stimulation in a long agonist protocol, the odds of achieving a clinical pregnancy were reduced by 13% and of achieving cryopreservation by 16%. In the antagonist protocol group, the length of ovarian stimulation did not have an effect on the clinical pregnancy and cryopreservation rates. CONCLUSIONS: Longer duration of ovarian stimulation appears to reduce clinical pregnancy and embryo cryopreservation rates in subjects undergoing long GnRH agonist cycles. The number of days of stimulation does not appear to affect those using the GnRH antagonist protocol.

Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

OBJECTIVE: Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. METHODS: We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. RESULTS: A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). CONCLUSION: The administration of growth hormone during the luteal phase before a microdose GnRH agonist flare protocol for in vitro fertilization did not improve outcomes in "poor responder" patients.

Objectif : L'hormone de croissance (GH) agit pendant le développement folliculaire tant précoce que tardif pour stimuler la prolifération et la différenciation des cellules de la granulosa, ainsi que pour accroître la production d'estradiol par les ovaires chez l'animal et l'homme. Les chercheurs se sont donc penchés sur le recours à la supplémentation en GH pour améliorer les issues chez les femmes qui font appel à la fécondation in vitro, tout en portant une attention particulière aux femmes qui présentent une réserve ovarienne amoindrie. De récentes méta-analyses indiquent que la supplémentation en GH peut être bénéfique pour les femmes qui réagissent mal à la FIV. Dans la plupart des études, on administre de la GH de façon concomitante avec des gonadotrophines pendant la phase folliculaire; cette façon de faire pourrait ne pas être optimale, puisque le recrutement folliculaire débute au cours de la phase lutéale qui précède. Nous avons donc souhaité examiner l'effet de la supplémentation en GH pendant la phase lutéale, avant la tenue d'une stimulation ovarienne contrôlée (SOC) au moyen d'un « protocole de poussée ¼ faisant appel à une microdose d'agoniste de la GnRH (MDF), chez des femmes qui font l'objet d'une fécondation in vitro. Méthodes : Nous avons mené une étude cas-témoins appariés rétrospective se penchant sur des patientes qui ont fait l'objet d'un traitement au sein d'un établissement privé de FIV entre juin 2012 et juillet 2013. Les patientes identifiées comme réagissant mal à la SOC se sont vu offrir un traitement adjuvant à la GH dans le cadre de leur schéma thérapeutique de stimulation ovarienne. Les patientes du groupe expérimental ont choisi de recevoir de la GH, à raison de 3,33 mg par jour sous forme d'injection sous-cutanée pendant 14 jours, avant le début de la SOC. Toutes les patientes ont fait l'objet d'un protocole de stimulation MDF faisant appel à 450 UI d'hormone folliculostimulante (FSH) par jour. Résultats : Au total, 42 femmes ont participé à l'étude. Le groupe expérimental (GH) comptait 14 femmes et le groupe témoin (C) comptait 28 femmes appariées en fonction de l'âge, de l'IMC et du taux de FSH au jour 3. Aucune différence n'a été constatée entre les groupes en matière de taux de grossesse clinique (GH = 29 %, C = 32 %, P = 0,99), de nombre d'ovocytes matures récupérés (GH = 2,5, C = 5,0, P = 0,13), de taux d'annulation de cycle (GH = 21 %, C = 14 %, P = 0,88), de durée de la SOC (GH = 10,1, C = 10,1, P = 0,93) ou de niveau moyen du pic d'estradiol (GH = 4 174 pmol/l, C = 5 105 pmol/l, P = 0,44). Conclusion : L'administration d'hormone de croissance pendant la phase lutéale, avant la mise en œuvre d'un « protocole de poussée ¼ faisant appel à une microdose d'agoniste de la GnRH aux fins de la fécondation in vitro, n'a pas permis d'améliorer les issues obtenues par les patientes « réagissant mal ¼ à la SOC.

Does endometrial injury improve implantation of frozen-thawed embryos?

PURPOSE: To investigate whether endometrial injury (EI) increases pregnancy rates in subjects undergoing frozen-thawed embryo transfer (FET) cycles. METHODS: We conducted a prospective study of 80 consecutive subjects at a private fertility center. All women were undergoing frozen embryo transfer after one or more unsuccessful in vitro fertilization and embryo transfer cycle(s). Subjects in the experimental group underwent endometrial biopsy in the luteal phase of the cycle preceding the frozen embryo transfer cycle. The primary outcomes were chemical and clinical pregnancy rates. RESULTS: The 40 subjects who underwent EI in the cycle preceding their FET cycle were compared with 40 controls. There were differences in the groups' baseline characteristics; the average age was slightly higher and the duration of infertility was longer in the EI group. Chemical pregnancy rates between the two groups were similar, 27 % (range 17-40 %) in the injury group and 26 % (16-40 %) in the control group (OR for chemical pregnancy = 1.05, 95 % CI 0.42-2.12). The difference in clinical pregnancy rate was not statistically significant: 40 % (25-57 %) in the injury group versus 33 % (19-49 %) in the control group (OR for clinical pregnancy = 1.38, 95 % CI 0.55-3.46). CONCLUSIONS: Based on the results of this pilot study, EI in the luteal phase of the cycle preceding the frozen embryo transfer cycle does not appear to significantly improve implantation or clinical pregnancy rates.

Malignant ovarian Sertoli-Leydig cell tumor localized with selective ovarian vein sampling.

Sertoli-Leydig cell tumors (SLCT) are rare, comprising less than 0.5% of ovarian neoplasms. They are most often diagnosed in premenopausal women and may produce androgens, resulting in hirsuitism, voice deepening, frontal balding, terminal hair growth, and clitoromegaly. SLCT are malignant in 15%-20% of cases. We discuss a 25-year-old patient with persistent hyperandrogenemia. Noninvasive imaging cannot conclusively differentiate between SCLT and other diagnoses such as polycystic ovary syndrome, ovarian hyperthecosis, idiopathic hyperandrogenism, idiopathic hirsuitism, and 21-hydroxylase-deficient nonclassic adrenal hyperplasia. Selective ovarian vein sampling revealed a 15-fold greater testosterone production from the right ovary compared with the left, which guided appropriate surgical management.

Cerebral venous sinus thrombosis in a woman using the etonogestrel-ethinyl estradiol vaginal contraceptive ring: a case report.

BACKGROUND: The vaginal contraceptive ring is a hormonal contraceptive that releases etonogestrel and ethinyl estradiol. Cerebral venous sinus thrombosis (CVST) is a rare but serious complication of hormonal contraceptive use. CASE: We present a case of CVST in a 33-year-old nulligravid woman who was using a vaginal contraceptive ring. At the time of presentation, she had been using the ring for 18 months, having previously used oral contraceptives for 13 years. She had no additional risk factors for thrombosis apart from cigarette smoking. Despite vigorous management, the patient died from the effects of the CVST. CONCLUSION: The serious adverse effects of the vaginal contraceptive ring are not well known, although deep vein thrombosis, pulmonary embolism, and aortic thrombosis in association with use of the ring have been reported to Health Canada. Continuing post-market surveillance of thrombotic risk in users of the vaginal contraceptive ring is critical.

Acute postpartum pulmonary edema in a 23-year-old woman 5 days after cesarean delivery.

The presentation of acute dyspnea after pregnancy is rare, but should bring a number of important conditions to the mind of the attending physician. Pulmonary embolism, amniotic fluid embolism, pneumonia, aspiration and pulmonary edema are some of the potentially devastating causes that must be considered. The percentage of pregnancies that are complicated by acute pulmonary edema has been estimated to be 0.08%. The most common contributing factors include the administration of tocolytic agents, underlying cardiac disease, iatrogenic fluid overload and preeclampsia. No matter what the underlying pathology, prompt administration of appropriate resuscitation is always the first priority. Only after the patient has been stabilized can attention be turned to diagnosis and specific treatment. This case examines one such presentation and reviews some of the diagnostic possibilities.

Outcomes of elective labour induction and elective caesarean section in low-risk pregnancies between 37 and 41 weeks' gestation.

OBJECTIVE: To compare maternal and neonatal outcomes after elective induction of labour and elective Caesarean section with outcomes after spontaneous labour in women with low-risk, full-term pregnancies. METHODS: We extracted birth data from 1996 to 2005 from an obstetrical database. Singleton pregnancies with vertex presentation, anatomically normal, appropriately grown fetuses, and no medical or surgical complications were included. Outcomes after elective induction of labour and elective Caesarean section were compared with the outcomes after spontaneous labour, using chi-square and Student t tests and logistic regression. RESULTS: A total of 9686 women met the study criteria(3475 nulliparous, 6211 multiparous). The incidence of unplanned Caesarean section was higher in nulliparous women undergoing elective induction than in those with spontaneous labour (P < 0.001). Postpartum complications were more common in nulliparous and multiparous women undergoing elective induction (P < 0.001 and P < 0.01, respectively) and multiparous women undergoing elective Caesarean section, (P < 0.001). Rates of triage in NICU were higher in nulliparous women undergoing elective Caesarean section (P < 0.01), and requirements for neonatal free-flow oxygen administration were higher in nulliparous and multiparous women undergoing elective Caesarean section (P < 0.01 for each). Unplanned Caesarean section was 2.7 times more likely in nulliparous women undergoing elective induction of labour (95% CI 1.74 to 4.28, P < 0.001) and was more common among nulliparous and multiparous women undergoing induction of labour and requiring cervical ripening (P < 0. 001 and P < 0.05, respectively). CONCLUSION: Elective induction leads to more unplanned Caesarean sections in nulliparous women and to increased postpartum complications for both nulliparous and multiparous women. Elective Caesarean section has increased maternal and neonatal risks.