Rapid cycle deliberate practice (RCDP) has emerged as an effective teaching method for enhancing skill proficiency. This study introduces the characteristics and theoretical foundations of RCDP, explains key points in instructional design and implementation strategies, and provides a comprehensive analysis of its application in medical education. Additionally, the potential value and development prospects of RCDP in simulation-based medical education in China are explored. This study aims to provide theoretical support and practical guidance for the further promotion and deeper implementation of the RCDP teaching method in China.

Rapid cycle deliberate practice (RCDP) has emerged as an effective teaching method for enhancing skill proficiency. This study introduces the characteristics and theoretical foundations of RCDP, explains key points in instructional design and implementation strategies, and provides a comprehensive analysis of its application in medical education. Additionally, the potential value and development prospects of RCDP in simulation-based medical education in China are explored. This study aims to provide theoretical support and practical guidance for the further promotion and deeper implementation of the RCDP teaching method in China.

Adenomyosis is a common gynecological disease with the main clinical manifestations of pelvic pain, abnormal uterine bleeding and reproductive disorders. At present, there is no unified evaluation criteria and treatment plan for adenomyosis, so it is important to understand the molecular mechanism of adenomyosis. Transcriptomics explains the functional elements of the genome at a global level and reveals the molecular mechanisms in specific biological processes. In recent years, with the rapid development of transcriptomics analysis technology, a number of studies have explored the molecular mechanism of adenomyosis based on transcriptomics, identified biomarkers and potential therapeutic targets of adenomyosis, and provided a new perspective for the diagnosis and treatment of adenomyosis. This review focuses on the latest research advances in transcriptome analysis in adenomyosis.

Adenomyosis is a common gynecological disease with the main clinical manifestations of pelvic pain, abnormal uterine bleeding and reproductive disorders. At present, there is no unified evaluation criteria and treatment plan for adenomyosis, so it is important to understand the molecular mechanism of adenomyosis. Transcriptomics explains the functional elements of the genome at a global level and reveals the molecular mechanisms in specific biological processes. In recent years, with the rapid development of transcriptomics analysis technology, a number of studies have explored the molecular mechanism of adenomyosis based on transcriptomics, identified biomarkers and potential therapeutic targets of adenomyosis, and provided a new perspective for the diagnosis and treatment of adenomyosis. This review focuses on the latest research advances in transcriptome analysis in adenomyosis.

Objective:To explore the effect of clomiphene citrate (CC) with different dosages on the endometrial factor, number of oocytes retrieved, pregnancy outcomes and other factors in diminished ovarian reserve (DOR) patients with minimal stimulation/natural protocol.Methods:This was a retrospective cohort study. The patients who underwent minimal stimulation protocol of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) were divided into 4 groups. Group A: the patients had CC 50 mg/d from the third day of menstruation to the trigger day (1 457 cycles); group B: the patients had 50 mg/d from the third day of menstruation for 3 d (1 533 cycles); group C: the patients had CC 25 mg/d from the third day of menstruation to the trigger day (345 cycles); group D: the patients had CC 25 mg/d for 3 d (319 cycles). The general data, clinical results, pregnancy and delivery outcomes were compared between group A and group B, as well as group C and group D. Results:In the treatment of IVF/ICSI, the dosage of gonadotropin (Gn) used, number of dominant follicles, estradiol level, luteinizing hormone level, progesterone level, number of oocytes retrieved, rate of oocytes retrieved, number of fertilizations, number of transplantable embryos and whole embryo freezing rate in patients of group A were significantly higher than those in group B (all P<0.05). The endometrial thickness [7.10 (5.40,8.65) mm] and the ratio of endometrial type (A/A-B) on trigger day [70.70% (888/1 256)] of group B were significantly better than those of group A [6.00 (4.70,8.00) mm, P<0.001; 63.62% (649/1 020), P<0.001], and the fresh embryo transfer rate of group B was significantly higher than that of group A [20.00% (259/1 295) vs. 42.94% (584/1 360), P<0.001]. There were no statistical differences in the number of high-quality embryos and the rate of no embryo transfer between the two groups (both P>0.05). In group C and group D, the Gn used dosage, the number of dominant follicles, the estradiol level on trigger day, number of oocytes retrieved, embryos/cycles were significantly increased (all P<0.05), the endometrial thickness on trigger day of group D [7.00 (5.40, 8.60) mm] was significantly higher than that of group C [6.10 (5.00,7.93) mm, P<0.001], but there was no statistical difference of the ratio of endometrial type (A/A-B) between the two groups ( P=0.739). In addition, the luteinizing hormone and progesterone values on the trigger day in group C were significantly higher than those in group D ( P=0.014, P=0.005), but there were no significant differences in pre-ovulation rate and all embryos frozen rate between the two groups (all P<0.05), and the rate of fresh embryo transfer in group C [26.04% (75/288)] was significantly lower than that in group D [38.80% (97/250), P<0.001]. Finally, there were no significant differences in cumulative clinical pregnancy rate and fresh/frozen embryo transfer outcome between group A and group B as well as group C and group D (all P>0.05). Conclusion:The use of low-dose and short-time CC in minimal stimulation protocol does not change the final pregnancy outcome, while saving patients' economic and time costs, so it could be an appropriate project for DOR patients.

Objective:To evaluate the effects of recombinant luteinizing hormone (rLH) and human menopausal gonadotropins (hMG) supplementation on pregnancy outcomes for suboptimal ovarian responders undergoing follicular phase long protocol.Methods:The data of infertile patients who underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) for the first time with follicular phase long protocol from January 2017 to January 2020 in Reproductive Medicine Center of the First Affiliated Hospital of Nanjing Medical University Hospital were retrospectively cohort analyzed. Totally 2 336 patients with normal ovarian reserve were included in the study with suboptimal ovarian response to ovarian stimulation. According to the different exogenous LH supplementation, they were divided into hMG group ( n=1 558) and rLH group ( n=778). The clinical features and effects of ovulation induction were compared between the two groups and reproductive outcomes were compared in both fresh embryo transfer cycles and subsequent frozen-thawed embryo transfer (FET) cycles. Logistic regression analysis were performed to explore the relationship between different LH activity drugs supplementation and the cumulative live birth rate of suboptimal ovarian responders. Results:The basic characteristics such as age, infertility type and diagnosis, body mass index and biomarkers of ovarian reserve were comparable between the two groups (all P>0.05). Total dosage [(2 088.98±628.24) U] and duration [(12.22±2.29) d] of FSH used in the hMG group were significantly higher than those in the rLH group [(1 866.90±602.65) U, P<0.001; (11.89±2.37) d, P=0.001]. Total dosage [(537.30±484.49) U] and duration [(7.40±3.52) d] of LH used in the hMG group were significantly higher than those in the rLH group [(498.10±472.04) U, (5.67±3.78) d, P<0.001]. The serum LH levels on the first day [(0.78±0.77) U/L] and the sixth day [(0.81±0.49) U/L] of gonadotropin stimulation in the hMG group were higher than those in the rLH group [(0.67±0.32) U/L, P<0.001; (0.71±0.33) U/L, P=0.002]. However, the serum LH level was comparable on the trigger day between the two groups without significant difference ( P=0.303). The levels of serum estrodiol [(8 377.14±7 000.63) pmol/L] and progesterone [(3.84±2.18) nmol/L] on the trigger day were significantly higher in the hMG group than in the rLH group [(7 644.91±5 145.64) pmol/L, P=0.009; (3.14±1.80) ng/L, P<0.001]. The pregnancy outcomes including clinical pregnancy rates, abortion rates and live birth rates were comparable between the two groups in fresh embryo transfer cycles and the subsequent FET cycles (all P>0.05). The cumulative pregnancy rate (CPR) [89.46% (696/778)] and the cumulative live birth rate (CLBR) [78.02% (607/778)] in the rLH group were significantly higher than those in the hMG group [84.60% (1 318/1 558), P=0.001; 72.98% (1 137/1 558), P=0.008]. Multivariate logistic regression analysis showed that age was a risk factor for CLBR ( OR=0.930, 95% CI: 0.906-0.955, P<0.001) and antral follicle count ( OR=1.029, 95% CI: 1.005-1.054, P=0.018), total number of oocytes retrieved ( OR=1.064, 95% CI: 1.029-1.100, P<0.001), the number of embryos transferred ( OR=1.714, 95% CI: 1.293-2.272, P<0.001), the stage of embryos transferred ( OR=1.567, 95% CI: 1.243-1.975, P<0.001), endometrial thickness on transfer day ( OR=1.122, 95% CI: 1.077-1.170, P<0.001) and rLH supplementation ( OR=1.348, 95% CI:1.101-1.651, P=0.004) were protective factors for CLBR of suboptimal responders. Conclusion:For suboptimal ovarian responders with normal ovarian reserve, rLH supplementation may achieve a higher CLBR than hMG supplementation in follicular phase long protocol.

Objective:To explore the effect of clomiphene citrate (CC) with different dosages on the endometrial factor, number of oocytes retrieved, pregnancy outcomes and other factors in diminished ovarian reserve (DOR) patients with minimal stimulation/natural protocol.Methods:This was a retrospective cohort study. The patients who underwent minimal stimulation protocol of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) were divided into 4 groups. Group A: the patients had CC 50 mg/d from the third day of menstruation to the trigger day (1 457 cycles); group B: the patients had 50 mg/d from the third day of menstruation for 3 d (1 533 cycles); group C: the patients had CC 25 mg/d from the third day of menstruation to the trigger day (345 cycles); group D: the patients had CC 25 mg/d for 3 d (319 cycles). The general data, clinical results, pregnancy and delivery outcomes were compared between group A and group B, as well as group C and group D. Results:In the treatment of IVF/ICSI, the dosage of gonadotropin (Gn) used, number of dominant follicles, estradiol level, luteinizing hormone level, progesterone level, number of oocytes retrieved, rate of oocytes retrieved, number of fertilizations, number of transplantable embryos and whole embryo freezing rate in patients of group A were significantly higher than those in group B (all P<0.05). The endometrial thickness [7.10 (5.40,8.65) mm] and the ratio of endometrial type (A/A-B) on trigger day [70.70% (888/1 256)] of group B were significantly better than those of group A [6.00 (4.70,8.00) mm, P<0.001; 63.62% (649/1 020), P<0.001], and the fresh embryo transfer rate of group B was significantly higher than that of group A [20.00% (259/1 295) vs. 42.94% (584/1 360), P<0.001]. There were no statistical differences in the number of high-quality embryos and the rate of no embryo transfer between the two groups (both P>0.05). In group C and group D, the Gn used dosage, the number of dominant follicles, the estradiol level on trigger day, number of oocytes retrieved, embryos/cycles were significantly increased (all P<0.05), the endometrial thickness on trigger day of group D [7.00 (5.40, 8.60) mm] was significantly higher than that of group C [6.10 (5.00,7.93) mm, P<0.001], but there was no statistical difference of the ratio of endometrial type (A/A-B) between the two groups ( P=0.739). In addition, the luteinizing hormone and progesterone values on the trigger day in group C were significantly higher than those in group D ( P=0.014, P=0.005), but there were no significant differences in pre-ovulation rate and all embryos frozen rate between the two groups (all P<0.05), and the rate of fresh embryo transfer in group C [26.04% (75/288)] was significantly lower than that in group D [38.80% (97/250), P<0.001]. Finally, there were no significant differences in cumulative clinical pregnancy rate and fresh/frozen embryo transfer outcome between group A and group B as well as group C and group D (all P>0.05). Conclusion:The use of low-dose and short-time CC in minimal stimulation protocol does not change the final pregnancy outcome, while saving patients' economic and time costs, so it could be an appropriate project for DOR patients.

Objective:To evaluate the effects of recombinant luteinizing hormone (rLH) and human menopausal gonadotropins (hMG) supplementation on pregnancy outcomes for suboptimal ovarian responders undergoing follicular phase long protocol.Methods:The data of infertile patients who underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) for the first time with follicular phase long protocol from January 2017 to January 2020 in Reproductive Medicine Center of the First Affiliated Hospital of Nanjing Medical University Hospital were retrospectively cohort analyzed. Totally 2 336 patients with normal ovarian reserve were included in the study with suboptimal ovarian response to ovarian stimulation. According to the different exogenous LH supplementation, they were divided into hMG group ( n=1 558) and rLH group ( n=778). The clinical features and effects of ovulation induction were compared between the two groups and reproductive outcomes were compared in both fresh embryo transfer cycles and subsequent frozen-thawed embryo transfer (FET) cycles. Logistic regression analysis were performed to explore the relationship between different LH activity drugs supplementation and the cumulative live birth rate of suboptimal ovarian responders. Results:The basic characteristics such as age, infertility type and diagnosis, body mass index and biomarkers of ovarian reserve were comparable between the two groups (all P>0.05). Total dosage [(2 088.98±628.24) U] and duration [(12.22±2.29) d] of FSH used in the hMG group were significantly higher than those in the rLH group [(1 866.90±602.65) U, P<0.001; (11.89±2.37) d, P=0.001]. Total dosage [(537.30±484.49) U] and duration [(7.40±3.52) d] of LH used in the hMG group were significantly higher than those in the rLH group [(498.10±472.04) U, (5.67±3.78) d, P<0.001]. The serum LH levels on the first day [(0.78±0.77) U/L] and the sixth day [(0.81±0.49) U/L] of gonadotropin stimulation in the hMG group were higher than those in the rLH group [(0.67±0.32) U/L, P<0.001; (0.71±0.33) U/L, P=0.002]. However, the serum LH level was comparable on the trigger day between the two groups without significant difference ( P=0.303). The levels of serum estrodiol [(8 377.14±7 000.63) pmol/L] and progesterone [(3.84±2.18) nmol/L] on the trigger day were significantly higher in the hMG group than in the rLH group [(7 644.91±5 145.64) pmol/L, P=0.009; (3.14±1.80) ng/L, P<0.001]. The pregnancy outcomes including clinical pregnancy rates, abortion rates and live birth rates were comparable between the two groups in fresh embryo transfer cycles and the subsequent FET cycles (all P>0.05). The cumulative pregnancy rate (CPR) [89.46% (696/778)] and the cumulative live birth rate (CLBR) [78.02% (607/778)] in the rLH group were significantly higher than those in the hMG group [84.60% (1 318/1 558), P=0.001; 72.98% (1 137/1 558), P=0.008]. Multivariate logistic regression analysis showed that age was a risk factor for CLBR ( OR=0.930, 95% CI: 0.906-0.955, P<0.001) and antral follicle count ( OR=1.029, 95% CI: 1.005-1.054, P=0.018), total number of oocytes retrieved ( OR=1.064, 95% CI: 1.029-1.100, P<0.001), the number of embryos transferred ( OR=1.714, 95% CI: 1.293-2.272, P<0.001), the stage of embryos transferred ( OR=1.567, 95% CI: 1.243-1.975, P<0.001), endometrial thickness on transfer day ( OR=1.122, 95% CI: 1.077-1.170, P<0.001) and rLH supplementation ( OR=1.348, 95% CI:1.101-1.651, P=0.004) were protective factors for CLBR of suboptimal responders. Conclusion:For suboptimal ovarian responders with normal ovarian reserve, rLH supplementation may achieve a higher CLBR than hMG supplementation in follicular phase long protocol.

OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.
Adaptor Proteins, Signal Transducing/genetics* ; Aged ; China ; Female ; Homozygote ; Humans ; Hydatidiform Mole/pathology* ; Mutation ; Pedigree ; Pregnancy ; Sequence Deletion

Objective:To investigate the effects of supplementation of recombinant luteinized hormone (rLH) and its timing on pregnancy outcomes of patients at 35 years or older with follicular-phase long protocol.Methods:Clinical data of women undergoing in vitro fertilization or intracytoplasmic sperm injection with follicular-phase long protocol was collected and retrospectively analyzed in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2019. There were 558 patients at 35 years or older included in this study, and they were divided into three groups: group A was patients with only recombinant follicle stimulating hormone (rFSH) stimulation (127 cycles), group B was patients with rFSH plus rLH supplementation in the mid-follicular phase (141 cycles), and patients in group C received combined rFSH and rLH from the first day of ovarian stimulation (290 cycles). The basic characteristics of patients of each group were observed and the effects of ovarian simulation and pregnancy outcomes were compared among the three groups. Logistic regression model was performed to explore the association between different groups and pregnancy outcomes.Results:The basic characteristics such as age, duration of infertility, body mass index (BMI) and serum basic follicle stimulating hormone (FSH) were comparable among the three groups (all P>0.05). Anti-Müllerian hormone (AMH), antral follicles count (AFC) and basic luteinized hormone (LH) were significantly lower in group C compared to group A and group B (all P<0.05). There were statistically significant differences in initiation dosage, total dosage and duration of gonadotropin (Gn) among the three groups (all P<0.01), the initiation dosage, total dosage and duration of Gn were higher in group C than the other two groups. The number of oocytes retrieved and available embryos were significantly lower in group B and group C than group A (all P<0.001). In fresh embryo transfer cycles, significantly higher implantation rate (45.3%, 117/258) and clinical pregnancy rate (52.6%, 111/211) were found for group C when compared with group A and group B ( P=0.036, P=0.006). The live birth rate in fresh embryo transfer cycles was comparable among the three groups ( P=0.098). The implantation rate, clinical pregnancy rate and live birth rate in the subsequent frozen-thawed embryo transfer cycles did not differ significantly among the three groups (all P>0.05). There were no significantly differences in the cumulative pregnancy rate and the cumulative live birth rate among the three groups (all P>0.05). After adjusted for age, BMI, AMH, AFC, basic FSH and LH, total Gn dosage, endometrial thickness at transfer, number of oocytes retrieved, number of embryos transferred and stage of embryo transferred, in fresh embryo transfer cycles, the clinical pregnancy rate (adjusted OR=2.793, 95% CI: 1.512-5.162, P<0.001) and live birth rate (adjusted OR=2.324, 95% CI: 1.241-4.351, P=0.008) were higher in group C, while clinical pregnancy rate and live birth rate were similar between group B and group A in fresh embryo transfer cycles (all P>0.05); there was no significant difference in cumulative live birth rate among the three groups ( P>0.05). Conclusions:The supplementation of rLH from the first day of ovarian stimulation improves the pregnancy outcomes of patients at 35 years or older in fresh embryo transfer cycles during follicular-phase long protocol. However, the supplementation of rLH has no benefit on cumulative live birth rate.