Endometrial compaction is associated with increased clinical and ongoing pregnancy rates in unstimulated natural cycle frozen embryo transfers: a prospective cohort study.

PURPOSE: To investigate the association between endometrial compaction and pregnancy rates in unstimulated natural cycle frozen embryo transfers. DESIGN: A single-center prospective cohort study. Endometrial thickness by transvaginal ultrasound and blood progesterone levels on the day of ovulation and the day of embryo transfer were evaluated in patients undergoing natural cycle frozen embryo transfer. Compaction was defined as > 5% decrease in endometrial thickness between ovulation day and day of transfer. Clinical and ongoing pregnancy rates in cycles with and without compaction were compared. RESULTS: Seventy-one women were included, of which 44% had endometrial compaction, with similar rates when subdividing the patients by day of transfer (day 3 or day 5). Clinical and ongoing pregnancy rates were higher in the compaction group compared to the non-compaction group (0.58 vs. 0.16, P < 0.001; 0.52 vs. 0.13, P < 0.001 respectively). Subdividing by degree of compaction > 10% and > 15% revealed similar pregnancy rates as > 5%, with no added benefit to higher degrees of compaction. CONCLUSIONS: About half the patients in our study undergoing unstimulated natural cycle frozen embryo transfer experienced compaction of the endometrium, occurring as early as day 3 post-ovulation. This was significantly correlated with increased clinical and ongoing pregnancy rates.

Ovarian Dermoid Cysts Associated with Paraneoplastic Syndrome N-methyl-D-aspartic Acid Receptor Antibodies Encephalitis.

STUDY OBJECTIVE: To describe the incidence of ovarian dermoid cysts associated with paraneoplastic encephalitis syndrome due to N-methyl-D-aspartic acid (NMDA) receptor antibodies among women undergoing surgical resection of dermoid cysts. DESIGN: Retrospective cohort study. SETTING: University-affiliated department of obstetrics and gynecology. PATIENTS: All patients with pathology-proven ovarian dermoid cysts who underwent surgical resection in our department between January 2008 and December 2019. Their demographic, clinical, and surgical characteristics are described, with emphasis on cases diagnosed with anti-NMDA receptor encephalitis. INTERVENTIONS: Ovarian dermoid cyst resection by cystectomy or salpingo-oophorectomy. MEASUREMENTS AND MAIN RESULTS: A total of 233 patients were operated on for ovarian dermoid cysts, comprising 2 cases diagnosed with anti-NMDA receptor encephalitis (0.85%). Among the women without NMDA receptor encephalitis, the mean age was 33.3 ± 14.9 years, 84.0% were of reproductive age, 5.2% were premenarchal, and 10.8% were menopausal. The mean diameter of the dermoid cyst in this group was 77.3 ± 33.3-mm. The 2 patients diagnosed with anti-NMDA receptor encephalitis were 21 years old and 42 years old. The diameters of their dermoid cysts were 15-mm and 80-mm, respectively. The patients with anti-NMDA receptor encephalitis were managed with laparoscopic resection, plasmapheresis, intravenous immunoglobulins, and corticosteroids; 1 patient also received immunosuppressive treatment. Both recovered without significant neurologic sequela. CONCLUSION: Paraneoplastic syndrome due to NMDA receptor antibodies is a rare complication of dermoid cysts. This complication may occur in younger or older women, as well as in small- or large-diameter cysts. Thus, a high index of suspicion is required to correctly diagnose and treat women presenting with neurologic symptoms in the presence of dermoid cysts.

Ploidy of spermatogenic cells of men with non-mosaic Klinefelter's syndrome as measured by a computerized cell scanning system.

PURPOSE: This study aims to characterize the origin of testicular post-meiotic cells in non-mosaic Klinefelter's syndrome (KS). METHODS: The study included testicular tissue specimens from 11 non-mosaic KS patients, with (6 positive) and without (5 negative) spermatozoa presence. The obtained testicular cells were affixed and stained for morphology followed by fluorescence in situ hybridization (FISH) for centromeric probes X, Y, and 18. We used a computerized automated cell scanning system that enables simultaneous viewing of morphology and FISH in the same cell. RESULTS: A total of 12,387 cells from the positive cases, 11,991 cells from the negative cases, and 1,711 cells from the controls were analyzed. The majority of spermatogonia were 47, XXY in both the positive and negative KS cases (88.9 ± 4.76 % and 90.6 ± 4.58 %) as were primary spermatocytes (76.8 ± 8.14 % and 79.6 ± 7.30 %). The respective rates of secondary spermatocytes and post-meiotic cells (round, elongating spermatids and sperm cells) were 1.1 ± 1.39 % in the positive cases, 2.9 ± 3.33 % in the negative cases, compared to 67.6 ± 6.22 % in the controls (P < 0.02). Pairing of both 18 and XY homologous chromosomes in 46,XY primary spermatocytes was 2.5 ± 2.31 % and 3.4 ± 2.39 %, respectively, compared to 19.8 ± 8.95 % in the control group (P < 0.02) and in 47,XXY primary spermatocytes in 2.4 ± 3.8 % in the positive group and 3.2 ± 2.26 % in the negative group. CONCLUSIONS: This study presents data to indicate that the majority of primary spermatocytes in the testes of non-mosaic KS patients are 47,XXY and could possibly develop into post-meiotic cells.

GnRH agonist early follicular challenge test as a predictor of ovarian response in antagonist cycles for fertility preservation.

The aim of our study was to evaluate if the response to follicular GnRH agonist (GnRHa) trigger be used to predict intracycle ovarian response in GnRH antagonist cycles among women undergoing fertility preservation IVF. We conducted a prospective study of 146 GnRH antagonist oocyte pickup (OPU) cycles to evaluate GnRHa stimulation test (GAST). On day 2 of the cycle, basal E2 were measured, followed by injection of 0.2 mg GnRHa as part of the initial ovarian stimulation. 12 h later blood sampling was repeated (GAST E3). E2 response was used as test parameter. The major outcome was the number of mature cryopreserved oocytes. We found a linear correlation between both GAST E3 level and GAST E3/E2 ratio and number of M2 oocytes. ROC curve analysis of GAST E3, GAST E3/E2 ratio, AFC and day 3 FSH for > 15 M2 and < 5 M2 oocytes was calculated. For GAST E3 levels obtaining < 5 M2 oocytes, an AUC value of 0.79 was found. For GAST E3 levels obtaining > 15 M2 oocytes, AUC value of 0.8. Patients with GAST E3 ≤ 384 pmol/l has 58.6% risk to obtain < 5 oocytes. Patients younger than 35 with GAST E3 > 708 pmol/l have 66% chance for freezing > 15 oocytes. The response to single GnRHa administration during GnRH antagonist cycle can be used as biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict the response of the specific cycle, and can potentially be used to adjust the treatment dose.Trial registration number: 0304-20-ASF.

Follicular challenge test to predict suboptimal response to gonadotropin releasing hormone agonist trigger in elective oocyte cryopreservation cycles.

This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10-12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the number of frozen oocytes was progesterone levels post agonist trigger (r = 0.746, p < 0.001). We concluded that suboptimal response to agonist trigger, as assessed by post trigger LH levels was a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate LH levels elevation after agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders.

Coronavirus disease 2019 vaccination and infertility treatment outcomes.

OBJECTIVE: To assess the influence of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid vaccine on ovarian response and in vitro fertilization (IVF) treatment outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary university-affiliated medical center and a private medical center. PATIENT(S): The study included a total of 400 patients, 200 vaccinated women and 200 age-matched unvaccinated women, who underwent IVF in January-April 2021. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The mean number of oocytes retrieved and clinical pregnancy rates in vaccinated vs. unvaccinated patients. RESULT(S): A total of 200 patients underwent oocyte retrieval 14-68 days after receiving COVID-19 vaccination. No difference was found in the mean number of oocytes retrieved per cycle (10.63 vs. 10.72) between vaccinated and unvaccinated patients. Among 128 vaccinated and 133 unvaccinated patients who underwent fresh embryos transfers, no difference was demonstrated in the clinical pregnancy rates (32.8% vs. 33.1%), with 42 and 44 clinical pregnancies, respectively. The fertilization rates and mean number of cryopreserved embryos were similar between the 2 groups in freeze-all cycles (55.43% vs. 54.29% and 3.59 vs. 3.28, respectively). Among vaccinated and unvaccinated patients who underwent fresh embryo transfers, no difference was noted in the fertilization rate (64.81% vs. 61.98%) and transferred embryos' quality. Regression models applied demonstrated no effect of the vaccine on oocyte yields and pregnancy rates. CONCLUSION(S): The COVID-19 messenger ribonucleic acid vaccine did not affect the ovarian response or pregnancy rates in IVF treatment. Women should be vaccinated for COVID-19 before attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women.

Feasibility of fertility preservation in young females with Turner syndrome.

Women with Turner syndrome (TS) are at risk of premature ovarian failure. The objective of this retrospective study was to identify patients with TS who could be potential candidates for fertility preservation and to determine their present reproductive and fertility status. Criteria for fertility preservation included: (i) spontaneous menarche; (ii) confirmation by ultrasound examination of the presence of at least one normal ovary; and (iii) serum FSH concentrations below 40 IU/l. Using the Montreal Children's Hospital Cytogenetic Database from 1990 to 2006, 28 patients with complete or partial absence of one X chromosome were identified: 13 (46%) were 45,X; nine (32%) had mosaic karyotypes; and six (21%) had karyotypes containing isochromosome or ring X chromosome. Six patients (21%) had spontaneous pubertal development and four (14%) were identified as potential candidates for fertility preservation. One underwent an ovarian stimulation protocol of gonadotrophin-releasing hormone agonist down-regulation followed by recombinant FSH and human menopausal gonadotrophin stimulation. Two metaphase-II-stage oocytes were aspirated and vitrified using the McGill Cryoleaf vitrification system. Another patient conceived spontaneously at the age of 24 years. In conclusion, fertility preservation may not be feasible for most patients with TS. However, after careful consideration of increased pregnancy-associated risks, fertility preservation may be offered to young females with mosaic TS.

A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles.

BACKGROUND: Our aim was to evaluate whether extending the interval between human chorionic gonadotrophin (hCG) priming and immature oocyte retrieval increases the oocyte maturation rate following in vitro maturation (IVM). METHODS: This study was performed retrospectively. IVM was performed on 113 polycystic ovary syndrome patients (n = 120 cycles). Oocyte collection was performed either 35 h (Group 1; n = 76) or 38 h (Group 2; n = 44) after 10,000 IU of hCG priming. Following oocyte retrieval, oocyte maturity was assessed and the remaining immature oocytes were cultured in IVM medium up to Day 2. RESULTS: The number of in vivo matured oocytes collected was significantly higher in Group 2 (13.6%, 114/840 versus 7.3%, 96/1312 in Group 1) (P < 0.01); the oocyte maturation rate after Day 1 was significantly higher (P < 0.01) in Group 2 (46.3 versus 36.0% in Group 1); and clinical pregnancy (40.9 versus 25%) and implantation rates (15.6 versus 9.6%) were better in Group 2 than those in Group 1. CONCLUSIONS: The results suggest that extending the period of hCG priming time from 35 to 38 h for immature oocyte retrieval promotes oocyte maturation in vivo and increases the IVM rate of immature oocytes. Therefore, oocyte retrieval after 38 h of hCG priming may improve subsequent pregnancy outcome in cycles programmed for IVM treatment.

Infertility, bilateral multicystic serous cystadenoma and pregnancy.

This article presents a case of bilateral and multicystic serous cystadenoma that appears to return immediately after complete excision of the cysts. Its presence did not impair ovarian response to FSH stimulation, or the occurrence of pregnancy and delivery.

Fertility preservation in patients with non-oncological conditions.

In addition to cancers, many non-oncological conditions, including chromosomal abnormalities and autoimmune disorders, are currently treated with gonadotoxic agents that can lead to premature ovarian failure. Because of the young age of some of the women affected by these conditions, attempts to preserve fertility and ovarian function are recommended. To date, retrieval of immature oocytes followed by in-vitro maturation and vitrification has been found to be especially useful for women who cannot undergo ovarian stimulation, or when there is a contraindication.

Immature oocyte retrieval in the luteal phase to preserve fertility in cancer patients.

As cancer treatment outcomes improve, the number of women with cancer seeking fertility preservation increases. Currently, embryo/oocyte cryopreservation appears to provide the best fertility preservation option. However, patients may not have sufficient time to undergo ovarian stimulation prior to chemotherapy and/or the hormones used in ovarian stimulation are contraindicated for certain tumours. In-vitro maturation has been suggested as an effective treatment for these patients. This report presents three women aged 21, 30 and 40 years, without male partners, seeking fertility preservation prior to chemotherapy. They were first seen during the luteal phase of their menstrual cycle and were to undergo gonadotoxic treatment imminently. They underwent immature oocyte retrieval in the luteal phase and seven, five and seven immature oocytes were recovered, respectively. After in-vitro maturation, five, three and five metaphase II (MII) oocytes were vitrified. Two patients later underwent one and two more retrievals, respectively, in the follicular phase of the next cycle(s) and additional oocytes were cryopreserved. These results suggest that immature oocytes recovered in the luteal phase can successfully be matured in vitro; therefore, if there is not sufficient time for conventional follicular-phase oocyte retrieval in a stimulated/unstimulated cycle prior to chemotherapy, a retrieval in the luteal phase could be considered.

Extrauterine mislocated IUD: is surgical removal mandatory?

The incidence of intrauterine device perforation is 0.87 per 1000 insertions. An intrauterine device (IUD) may perforate through the uterine wall into the pelvic or abdominal cavity or into adjacent organs. The accepted treatment for displaced IUDs is surgical removal because of the putative risk of adhesion formation or of damage to the intestine or urinary bladder. The purpose of this article is to present three cases of IUD perforation where surgical removal may not have been necessary. In all three cases, the IUD was removed by laparoscopy. No adhesions were found in any of the patients. Criteria for the surgical removal of a displaced IUD, as a result of uterine perforation, should be re-evaluated. Whilst surgical procedures to remove a misplaced IUD must be performed on symptomatic patients, asymptomatic patients, under certain circumstances, may benefit from conservative management.

Ovarian response to stimulation for fertility preservation in women with malignant disease: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the current available data regarding ovarian performance of patients diagnosed with malignant disease undergoing controlled ovarian hyperstimulation (COH) for fertility preservation, before radio/chemotherapy, compared with age-matched, healthy patients undergoing COH for in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). DESIGN: Meta-analysis of the data available from a systematic review of the literature. SETTING: Academic centers of infertility and IVF. PATIENT(S): Patients with malignant disease, before radio/chemotherapy, undergoing COH for fertility preservation within comparative studies with healthy, age-matched controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Peak estradiol levels on day of human chorionic gonadotropin administration, number of oocytes retrieved, fertilization rate, incidence of low ovarian response, and cycle cancellation. RESULT(S): Only seven retrospective, case-controlled studies were found to match our objective. Overall, the results of the meta-analysis indicate that the number of retrieved oocytes rate was statistically significantly lower compared with age-matched healthy IVF patients. The incidence of poor ovarian performance and risk of cycle cancellation as well as the calculated number of two pronuclei zygotes achieved among patients with cancer were comparable with their age-matched controls. CONCLUSION(S): Women with malignant disease should expect a lower number of oocytes retrieved after COH for fertility preservation, compared with healthy, age-matched patients. Presently, there is paucity of evidence to assess the effect of a specific malignant disease on ovarian response to COH before IVF for fertility preservation. Multicentric studies should be conducted to resolve these important issues.

In vitro fertilization surrogacy in rare coexisting Mayer-Rokitansky-Kuster-Hauser syndrome and triple X karyotype.

OBJECTIVE: To report the responses to IVF surrogacy attempts in a female with a heretofore never described combination of Mayer-Rokitansky-Kuster-Hauser (MRHK) syndrome and triple X karyotype. DESIGN: Case report. SETTING: Reproductive unit of a university-affiliated medical center. PATIENT(S): A 29-year-old female diagnosed as having both MRHK syndrome and a triple X (47XXX) karyotype. INTERVENTION(S): Five cycles of IVF surrogacy. MAIN OUTCOME MEASURE(S): Recovery of oocytes after controlled ovarian stimulation. RESULT(S): A maximum of five oocytes were retrieved by percutaneous abdominal aspiration of a single subcostal left ovary. After five unsuccessful IVF trials due to low ovarian response attributed to her coexisting MRHK syndrome and triple X karyotype, the patient's choice was oocyte donation. CONCLUSION(S): An abnormal karyotype can coexist with MRKH syndrome, albeit very rarely, and probably accounts for a low ovarian response to attempts to achieve IVF surrogacy.

Retrieval of immature oocytes from unstimulated ovaries followed by in vitro maturation and vitrification: A novel strategy of fertility preservation for breast cancer patients.

BACKGROUND: We report a novel fertility preservation strategy that may be useful for young breast cancer patients who present with time constraints or concerns about the effect of ovarian stimulation. METHODS: The protocol involves retrieval of immature oocyte from unstimulated ovaries followed by in vitro maturation (IVM), and vitrification of oocytes or embryos. RESULTS: Thirty-eight patients (age 24-45 years) underwent vitrification of oocytes (n = 18) or embryos (n = 20). The mean ages were 33.1 +/- 5.0 years and 34.7 +/- 4.8 years, respectively. The mean days required to complete the egg collection was 13 days. The median numbers of vitrified oocytes and embryos per retrieval were 7 (range 1-22) and 4 (range 1-13), respectively. CONCLUSIONS: The strategy of immature oocyte retrieval without ovarian stimulation followed by IVM and oocyte or embryo vitrification, which does not increase the serum estradiol level and delay cancer treatment, represents an attractive option of fertility preservation for many breast cancer patients.

Cryopreservation of oocytes in a young woman with severe and symptomatic endometriosis: a new indication for fertility preservation.

OBJECTIVE: To report a new indication for fertility preservation. DESIGN: Case report. SETTING: Academic teaching hospital. PATIENT(S): A 25-year-old nulliparous woman with severe and symptomatic endometriosis and low antral follicular count. INTERVENTION(S): Oocyte cryopreservation. MAIN OUTCOME MEASURE(S): Number of cryopreserved oocytes. RESULT(S): After three cycles of ovarian stimulation, we cryopreserved 21 oocytes. CONCLUSION(S): We recommend fertility preservation as part of preoperative counseling in young women with severe endometriosis.

Comparison of low-dose human menopausal gonadotropin and micronized 17beta-estradiol supplementation in in vitro maturation cycles with thin endometrial lining.

OBJECTIVE: A challenge of in vitro maturation (IVM) treatment in some women is insufficient development of the endometrium prior to embryo transfer. DESIGN: Retrospective study. SETTING: McGill Reproductive Center, Montreal, Canada. PATIENT(S): Women with endometrial thickness <6 mm on days 6-10 ultrasound (US) scan of IVM treatment. INTERVENTION(S): In the human menopausal gonadotropin (hMG) group, 150 IU/day of hMG was started and in the estradiol group, 6 to 12 mg/day of micronized 17beta-estradiol was initiated. Additional US scans were performed 2 to 3 days apart, until endometrial thickness reached > or =8 mm or a dominant follicle (>10 mm) was identified. MAIN OUTCOME MEASURE(S): Endometrial lining before oocyte retrival. RESULT(S): In both groups endometrial lining significantly thickened following treatment. However, hMG treatment resulted in a higher number of follicles > or =7 mm compared to estradiol (7.4 +/- 4.8 vs. 3.4 +/- 2.5, respectively) and a significantly higher percentage of mature oocytes that were identified on the day of oocyte retrieval (in vivo matured oocytes) (15.1% vs. 10.5%). CONCLUSION(S): In IVM designated cycles with a thin endometrium both low-dose hMG and micronized 17beta-estradiol supplementation significantly improve endometrial thickness. However, low-dose hMG results in larger follicles and a greater number of in vivo matured oocytes.

Comparison of survival rate of cleavage stage embryos produced from in vitro maturation cycles after slow freezing and after vitrification.

Significantly more embryos survived the vitrification procedure compared to slow freezing (85.5% vs. 61.8%) in cleavage-stage human embryos produced from in vitro maturation cycles, suggesting that vitrification is more efficient than slow freezing for cryopreservation.

Cryopreservation of a mother's oocytes for possible future use by her daughter with Turner syndrome: case report.

OBJECTIVE: To report a new fertility alternative for women with Turner syndrome, who are rendered infertile, by having their mothers freeze their own oocytes for the purpose of donating to their daughters when they are adults. DESIGN: Case report. SETTING: Academic teaching hospital. PATIENT(S): A 33-year-old healthy mother of three children; and her second child, a 6-year-old daughter recently diagnosed with Turner syndrome. INTERVENTION(S): Mother-to-daughter oocyte donation combined with oocyte vitrification. MAIN OUTCOME MEASURE(S): Number of cryopreserved oocytes. RESULT(S): After three cycles of ovarian stimulation, 30 oocytes were cryopreserved for the daughter's possible future use. CONCLUSION(S): The treatment option presented here opens the door for the banking of a mother's oocytes as a possible donation to a young daughter with a medical condition that leads to infertility, for her possible future use.