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Objective@#The purpose of this study was to use a mouse model to investigate the blastocyst formation rate in vitrified-warmed embryos derived from vitrified-warmed oocytes. @*Methods@#Metaphase II oocytes obtained from BDF1 mice were vitrified and warmed, followed by fertilization with epididymal sperm. On day 3, a total of 176 embryos, at either the eight-cell or the morula stage, were vitrified-warmed (representing group 1). For group 2, 155 embryos at the same developmental stages were not vitrified, but rather were directly cultured until day 5. Finally, group 3 included day-5 blastocysts derived from fresh oocytes, which served as fresh controls. The primary outcome measured was the rate of blastocyst formation per day-3 embryo at the eight-cell or morula stage. @*Results@#The rates of blastocyst formation per day-3 embryo were comparable between groups 1 and 2, at 64.5% and 69.7%, respectively (p>0.05). The formation rates of good-quality blastocysts (expanded, hatching, or hatched) were also similar for groups 1 and 2, at 35.5% and 43.2%, respectively (p>0.05). For the fresh oocytes (group 3), the blastocyst formation rate was 75.5%, which was similar to groups 1 and 2. However, the rate of good-quality blastocyst formation in group 3 was 57.3%, significantly exceeding those of group 1 (p=0.001) and group 2 (p=0.023). @*Conclusion@#Regarding developmental potential to the blastocyst stage, vitrified-warmed day-3 embryos originating from vitrified-warmed oocytes demonstrated comparable results to non-vitrified embryos from similar oocytes. These findings indicate that day-3 embryos derived from vitrified-warmed oocytes can be effectively cryopreserved without incurring cellular damage.
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This article reports the live birth of a healthy newborn using vitrified-warmed oocytes from fertility preservation before ovarian surgery. The patient in our case underwent two cycles of controlled ovarian stimulation before laparoscopic bilateral ovarian cystectomy for endometriosis, and a total of 23 mature oocytes were vitrified. After surgery, her pathologic reports revealed a serous borderline tumor and endometrioma. Fifteen months after her second surgery of laparoscopic right salpingo-oophorectomy and left ovarian cystectomy owing to recurrence, she had been married by then, and three of the frozen oocytes were thawed for intracytoplasmic sperm injection. These oocytes were cryopreserved for 2.5 years. All three were fertilized, and two grade-A cleavage-stage embryos were transferred.A singleton pregnancy was achieved, resulting in the delivery of a healthy baby boy at 39.3 weeks of gestation. Oocyte cryopreservation is an effective method for fertility preservation prior to ovarian surgery when ovarian function decline is predictable.
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Fertility preservation is a major concern in young patients diagnosed with breast cancer and planning to receive multimodality treatment, including gonadotoxic chemotherapy with or without age-related decline through long-term endocrine therapy. Most breast cancer patients undergo multimodality treatments; many short-term and long-term side effects arise during these therapies. One of the most detrimental side effects is reduced fertility due to gonadotoxic treatments with resultant psychosocial stress. Cryopreservation of oocytes, embryos, and ovarian tissue are currently available fertility preservation methods for these patients. As an adjunct to these methods, in vitro maturation or gonadotropinreleasing hormone agonist could also be considered. It is also essential to communicate well with patients in the decision-making process on fertility preservation. It is essential to refer patients diagnosed with breast cancer on time to fertility specialists for individualized treatment, which may lead to desirable outcomes. To do so, a multimodal team-based approach and in-depth discussion on the treatment of breast cancer and fertility preservation is crucial. This review aims to summarize infertility risk related to currently available breast cancer treatment, options for fertility preservation and its details, barriers to oncofertility counseling, and psychosocial issues.
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As the number of cancer survivors has increased with advancements in cancer treatment, fertility preservation has become a treatment goal. Ovarian tissue cryopreservation (OTC) and transplantation (OTT) has made great progress over the past few decades. It has become the treatment of choice for fertility preservation in adolescents or patients in urgent need of chemotherapy. However, it is considered to be experimental compared with oocyte or embryo cryopreservation in some countries. Nevertheless, OTC and OTT is regarded as the more ideal method for fertility preservation in that it can also restore hormonal functions.Current Concepts: Currently, over 200 live births have been reported worldwide after OTC and OTT, proving the excellence of the technology. However, before its application in clinical settings, some challenges, including cryoinjury, ischemic injury, and cancer cell reimplantation, should be overcome. For cryoinjury, studies are underway on protocol improvement with the addition of agents such as antifreeze protein during cryopreservation. For ischemic injury, various agents have been studied to promote angiogenesis or revascularization. Furthermore, studies are underway on artificial ovary or xenotransplantation for fertility preservation in an effort to avoid cancer cell metastasis.Discussion and Conclusion: OTC and OTT is a clinically applicable option for fertility preservation. To set OTC and OTT as an established method for fertility preservation, further research is necessary to overcome the current challenges.
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We investigated the impact of vitamin D3 (VD3) supplementation during mouse preantral follicle culture in vitro and the mRNA expression of 25-hydroxylase (CYP2R1), 1-alpha-hydroxylase (CYP27B1), and vitamin D receptor (VDR) in mouse ovarian follicles at different stages. Methods: Preantral follicles were retrieved from 39 BDF1 mice (7–8 weeks old) and then cultured in vitro for 12 days under VD3 supplementation (0, 25, and 50 pg/mL). Follicular development and the final oocyte acquisition were assessed. Preantral follicles were retrieved from 15 other BDF1 mice (7–8 weeks old) and cultured without VD3 supplementation. Three stages of mouse ovarian follicles were obtained (preantral, antral, and ruptured follicles). Total RNA was extracted from the pooled cells (from 20 follicles at each stage), and then reverse transcriptase-polymerase chain reaction was performed to identify mRNA for CYP2R1, CYP27B1, and VDR. Results: The survival of preantral follicles, rates of antrum formation and ruptured follicles (per initiated follicle) and the number of total or mature oocytes were all comparable among the three groups. Both CYP2R1 and CYP27B1 were expressed in antral and ruptured follicles, but not in preantral follicles. VDR was expressed in all three follicular stages. Conclusion: VD3 supplementation in vitro (25 or 50 pg/mL) did not enhance mouse follicular development or final oocyte acquisition. Follicular stage-specific expression of CYP2R1, CYP27B1, and VDR was observed.
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Objective@#We investigated the impact of tyrosine kinase inhibitor (imatinib or dasatinib) coadministration with cyclophosphamide (Cp) on preantral follicle development in an in vitro mouse model. @*Methods@#Seventy-three female BDF1 mice were allocated into 4 experimental groups: group A, saline; group B, Cp (25 mg/kg); group C, Cp (25 mg/kg) and imatinib (7.5 mg/kg); and group D, Cp (25 mg/kg) and dasatinib (7.5 mg/kg). Preantral follicles were isolated and cultured in vitro up to 12 days. Final oocyte acquisition and spindle integrity of metaphase II (MII) oocytes were assessed. Levels of 17β-estradiol and anti-Müllerian hormone (AMH) in the final spent media were measured by enzyme-linked immunosorbent assays, and the mRNA levels of Star, Sod1, Mapk3, and Casp3 in the final follicular cells were quantified by real-time polymerase chain reaction. @*Results@#The percentage of MII oocytes per initiated follicle, the proportion of MII oocytes with normal spindles, and the 17β-estradiol level were similar in all four groups. The median AMH level in group B (7.74 ng/mL) was significantly lower than that in group A (10.84 ng/mL). However, the median AMH levels in group C (9.96 ng/mL) and group D (9.71 ng/mL) were similar to that in group A. The mRNA expression levels of Star, Sod1, Mapk3, and Casp3 were similar in all four groups. @*Conclusion@#Coadministration of imatinib or dasatinib with Cp could preserve AMH production capacity in this in vitro mice preantral follicle culture model, and it did not affect MII oocyte acquisition.
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Objective@#We investigated the impact of tyrosine kinase inhibitor (imatinib or dasatinib) coadministration with cyclophosphamide (Cp) on preantral follicle development in an in vitro mouse model. @*Methods@#Seventy-three female BDF1 mice were allocated into 4 experimental groups: group A, saline; group B, Cp (25 mg/kg); group C, Cp (25 mg/kg) and imatinib (7.5 mg/kg); and group D, Cp (25 mg/kg) and dasatinib (7.5 mg/kg). Preantral follicles were isolated and cultured in vitro up to 12 days. Final oocyte acquisition and spindle integrity of metaphase II (MII) oocytes were assessed. Levels of 17β-estradiol and anti-Müllerian hormone (AMH) in the final spent media were measured by enzyme-linked immunosorbent assays, and the mRNA levels of Star, Sod1, Mapk3, and Casp3 in the final follicular cells were quantified by real-time polymerase chain reaction. @*Results@#The percentage of MII oocytes per initiated follicle, the proportion of MII oocytes with normal spindles, and the 17β-estradiol level were similar in all four groups. The median AMH level in group B (7.74 ng/mL) was significantly lower than that in group A (10.84 ng/mL). However, the median AMH levels in group C (9.96 ng/mL) and group D (9.71 ng/mL) were similar to that in group A. The mRNA expression levels of Star, Sod1, Mapk3, and Casp3 were similar in all four groups. @*Conclusion@#Coadministration of imatinib or dasatinib with Cp could preserve AMH production capacity in this in vitro mice preantral follicle culture model, and it did not affect MII oocyte acquisition.
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Objective@#To investigate whether the degree of post-warming embryo or blastocyst development is associated with clinical pregnancy in vitrified embryo or blastocyst transfer cycles. @*Methods@#Ninety-six vitrified cleavage-stage embryos and 58 vitrified blastocyst transfer cycles were selected. All transfer cycles were performed from February 2011 to March 2019, and all vitrified embryos or blastocysts were warmed from 4 PM to 6 PM and then transferred the next morning from 9 AM to 10 AM. The scores of the cleavage-stage embryos and blastocysts were assessed at warming and at transfer using the modified Steer method and the Gardner method, respectively. The mean embryo or blastocyst score, score of the single top-quality embryo or blastocyst, and the difference in the score between warming and transfer were compared between nonpregnant and pregnant women. @*Results@#In the cleavage-stage embryo transfer cycles, both the top-quality embryo score at transfer and the difference in the score between warming and transfer were significantly associated with clinical pregnancy. A top-quality embryo score at transfer of ≥60.0 (area under the curve [AUC], 0.673; 95% confidence interval [CI], 0.531–0.815) and a difference in the score between warming and transfer of ≥23.0 (AUC, 0.675; 95% CI, 0.514–0.835) were significant predictors of clinical pregnancy. In blastocyst transfer cycles, the top-quality blastocyst score at transfer was the only significant factor associated with clinical pregnancy. A top-quality blastocyst score at transfer of ≥38.3 was a significant predictor of clinical pregnancy (AUC, 0.666; 95% CI, 0.525–0.807). @*Conclusion@#The top-quality embryo score at transfer and the degree of post-warming embryo development were associated with clinical pregnancy in vitrified cleavage-stage embryo transfer cycles. In vitrified blastocyst transfer cycles, the top-quality blastocyst score at transfer was the only significant factor affecting clinical pregnancy.
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Methods@#We selected 124 cycles from 100 women (under age 40 years) who underwent oocyte pick-up (number of trials ≤3, 4–14 oocytes obtained) and transfer of two or three day 3 or day 4 embryos at two infertility centers from January 2014 to June 2019. Dual P (intramuscular P [50 mg] daily+vaginal P) was used in 52 cycles and a single intramuscular administration of P (50 mg daily) was used in 72 cycles. @*Results@#Women’s age, infertility factors, number of oocytes retrieved, number of transferred embryos, and mean embryo score were similar between the dual P group and the single P group. Although the number of trial cycles was significantly higher (1.9 vs. 1.5), and the mean endometrial thickness on the trigger day (10.0 mm vs. 11.0 mm) was significantly lower in the dual P group, the implantation rate, clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate for both day 3 and day 4 transfers were similar between the two groups. @*Conclusion@#In fresh day 3 or day 4 embryo transfer cycles, dual P administration did not demonstrate any clinical advantages. Intramuscular P alone appears to be sufficient for luteal support.
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Methods@#We selected 210 fresh IVF cycles performed in 170 infertile women at a single center from January 2014 to November 2019. Four to 14 (total) oocytes were obtained in all cycles after conventional ovarian stimulation. A receiver operating characteristic curve analysis was performed to find the moderate and extreme cutoff numbers of mature oocytes that would produce ≥1, ≥2, ≥3, ≥4, and ≥5 top-quality embryos. @*Results@#The cutoff number of mature oocytes was significantly correlated with the number of top-quality embryos (r =0.467, p =0.000). The moderate cutoff number of mature oocytes was ≥3, ≥5, ≥5, ≥6, and ≥6 for obtaining ≥1, ≥2, ≥3, ≥4, and ≥5 top-quality embryos, respectively. The extreme cutoff number of mature oocytes was ≥9, ≥9, ≥10, ≥10, and ≥11 for obtaining ≥1, ≥2, ≥3, ≥4, and ≥5 top-quality embryos, respectively. @*Conclusion@#We present the optimal cutoff numbers of mature oocytes that would yield ≥1, ≥2, ≥3, ≥4, and ≥5 top-quality embryos with 95% specificity. Our findings could help infertility clinicians to set target mature oocyte numbers in women undergoing stimulated IVF cycles.
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OBJECTIVE: The aim of this study was to investigate the level of awareness and knowledge regarding elective oocyte cryopreservation (OC) among unmarried women of reproductive age in Korea. METHODS: A survey was conducted among 86 women who visited a fertility preservation clinic for counseling about elective OC between December 2016 and May 2018. Participants were asked to fill out a questionnaire regarding their awareness and knowledge of fertility and OC. RESULTS: The questionnaire was completed by 71 women. Among them, 73% decided to undergo OC after counseling. The main reason for making this decision was that they wished to maintain their fertility in the future (70.6%). Conversely, the high cost for the procedure was the main reason given by those who chose to forego this procedure. Regarding fertility and OC, the participants' knowledge was poor. Most women expected greater financial support from the government or from their place of employment. CONCLUSION: This study demonstrated that the awareness and knowledge about elective OC were relatively poor among the female Korean population. These findings may help clinicians in better counselling of their patients.
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Femenino , Humanos , Consejo , Criopreservación , Empleo , Preservación de la Fertilidad , Fertilidad , Apoyo Financiero , Corea (Geográfico) , Oocitos , Persona Soltera , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To investigate prevalence of antiphospholipid antibody (APA) in Korean infertile women undergoing the first in vitro fertilization (IVF) treatment and to evaluate the influence of APA on the subsequent IVF outcomes. METHOD: Two hundred nineteen infertile women who destined the first IVF were prospectively enrolled in 2 infertility centers. Male factor or uterine factor infertility and women with past or current endocrine or immunologic disorders were completely excluded. Plasma concentration of lupus anticoagulant was measured by clot-based method, and anticardiolipin antibody (IgG/IgM), and anti-β2-glycoprotein 1 antibody (IgG/IgM) was measured by enzyme-linked immunosorbent assay method before starting ovarian stimulation for IVF. RESULTS: APA was positive in 13 women (5.9%). Lupus anticoagulant was positive in 2 women (0.9%), anticardiolipin antibody was positive in 7 women (3.2%), and anti-β2-glycoprotein 1 antibody was positive in 4 women (1.8%). In 193 women entering embryo transfer, clinical characteristics and stimulation outcomes were comparable between APA-positive (n=12) and APA-negative group (n=181). The clinical pregnancy rate (66.7% vs. 45.9%), ongoing pregnancy rate (58.3% vs. 37.0%), and miscarriage rate (12.5% vs. 19.3%) were all similar between APA-positive and APA-negative group. CONCLUSION: The prevalence of APA is low in Korean infertile women undergoing the first IVF cycle, and the presence of APA appears to neither decrease their first IVF success nor increase abortion rate.
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Femenino , Humanos , Masculino , Embarazo , Aborto Inducido , Aborto Espontáneo , Anticuerpos Anticardiolipina , Anticuerpos Antifosfolípidos , Transferencia de Embrión , Ensayo de Inmunoadsorción Enzimática , Fertilización In Vitro , Técnicas In Vitro , Infertilidad , Inhibidor de Coagulación del Lupus , Métodos , Inducción de la Ovulación , Plasma , Índice de Embarazo , Prevalencia , Estudios ProspectivosRESUMEN
OBJECTIVE: To report an efficacy of gonadotropin releasing hormone (GnRH) antagonist administration after freezing of all embryos for treatment of early type ovarian hyperstimulation syndrome (OHSS). METHODS: In 10 women who developed fulminant early type OHSS after freezing of all embryos, GnRH antagonist (cetrorelix 0.25 mg per day) was started at the time of hospitalization and continued for 2 to 4 days. Fluid therapy and drainage of ascites was performed as usual. RESULTS: Early type OHSS was successfully treated without any complication. At hospitalization, the median (95% confidence interval [CI]) of the right and the left ovarian diameter was 10.0 cm (7.6 to 12.9 cm) and 8.5 cm (7.5 to 12.6 cm). After completion of GnRH antagonist administration, it was decreased to 7.4 cm (6.2 to 10.7 cm) (P=0.028) and 7.8 cm (5.7 to 12.2 cm) (P=0.116), respectively. The median duration of hospital stay was 6 days (3 to 11 days). Trans-abdominal drainage of ascites was performed in 2 women and drainage of ascites by percutaneous indwelling catheter was performed in 4 women. No side effect of GnRH antagonist was noted. CONCLUSION: GnRH antagonist administration appears to be safe and effective for women with fulminant early type OHSS after freezing all embryos. Optimal dose or duration of GnRH antagonist should be further determined.