Staged Treatment with Chinese Herbal Medicine in a Controlled Ovarian Hyperstimulation of In Vitro Fertilization-Embryo Transfer Programme / 中医杂志

It is believed that kidney deficiency is the fundamental pathogenesis while liver constraint and spleen deficiency， and disharmony of chong （thorough vessel， 冲脉）and ren （conception vessel， 任脉） is the key pathogenesis of infertility patients who adopted controlled ovarian hyperstimulation of in vitro fertilization-embryo transfer （IVF-ET） programme. Therefore， the method of tonifying the kidneys dominantly and treating the liver and spleen simultaneously is proposed， and Chinese herbal medicine is suggested to be used in adjuvant treatment of staged IVF-ET controlled ovrian hyperstimulation. In the regulation stage， modified Liuwei Dihuang Pill （六味地黄丸） can be used to tonify kidney and supplement essence， fortify spleen and nourish liver； in the ovulation promotion stage， modified Wenjing Decoction （温经汤） should be used to warm kidney and assist yang， dispel stasis and nourish blood； in the pre-transplantation endothelial preparation stage， modified Shenling Baizhu Powder （参苓白术散） is suggested to fortify spleen and replenish qi， invigorate blood and resolve stasis； after the transplantation stage， modified Shoutai Pill （寿胎丸） or Taiyuan Decoction （胎元饮） can be taken to fortify spleen and tonify kidney， benefit qi and nourish blood.

Is the length of time between endometrial scratching and embryo transfer important for pregnancy success? An observational study

SUMMARY OBJECTIVE: This study sought to evaluate the influence of time (early <90 days and late >90 days) and endometrial injury on pregnancy success. METHODS: This is a retrospective study in which all infertile women who underwent at least one in vitro fertilization cycle at Clinica Gera between 2010 and 2015 were considered for inclusion. We included patients with a normal ovarian reserve and regular menses at intervals of up to 30 days. A total of 315 patient files were reviewed, and the study group was composed of patients who faced fertility issues and had male-caused infertility or idiopathic infertility. Also, women with male or unknown cause of infertility who have performed endometrial biopsy and have undergone embryo transfer up to 180 days after this procedure between 2010 and 2015 were included. The patients were divided into two groups according to the interval between biopsy and embryo transfer: group 1 (early—an interval of <90 days) and group 2 (late—an interval of >90 days and up to 180 days). RESULTS: The results were superior for the group with an interval of less than 90 days relative to the group with an interval of more than 90 days (p<0.04). The pregnancy rates for group 1 and group 2 were 58.5% and 43.4%, respectively. The odds ratio for pregnancy success was 1.63 (95% confidence interval: 1.04 to 2.55). CONCLUSION: The early transfer of embryos (<90 days) may produce better results with a high rate of pregnancy. Further studies are necessary to identify the mechanism involved in this phenomenon.

Application progress of mobile health in nursing of patients with infertility / 中国实用护理杂志

This article firstly reviews the current application status of mobile health based on social networking media, mobile health applications, wearable devices in infertility patients′nursing. Then, this paper analyzes the application effects of mobile health in the five aspects of treatment process management, health education, medication management, lifestyle management and psychological care for infertility patients based on the literature. The existing problems are analyzed and prospected on this basis, in order to provide a reference for the application of mobile health to infertility patients′nursing in China.

Clinical Efficacy of Oral Dydrogesterone Alone in Natural Cycle Frozen-thawed Embryo Transfer / 中山大学学报(医学科学版)

ObjectiveTo investigate the clinical efficacy of oral dydrogesterone alone for luteal phase support in natural cycle frozen-thawed embryo transfer （NC-FET）. MethodsThe clinical data of 1 530 NC-FET cycles enrolled in our Reproductive Center from January 2019 to September 2021 were retrospectively analyzed. According to different luteal support protocols， the patients were divided into oral dydrogesterone alone （group A， n=524）， vaginal progesterone soft capsules （group B， n=401） and vaginal progesterone soft capsules combined with dydrogesterone （group C， n=605）. The clinical outcomes and cost-effectiveness ratio were compared among the three groups. The primary outcome was live birth rate. ResultsThe live birth rate was 43.13% （226/524） in group A， 39.15% （157/401） in group B， and 42.64% （258/605） in group C. There was no statistical difference among the three groups （P > 0.05）. No statistical difference was observed in the HCG positive rate， implantation rate， biochemical pregnancy rate， clinical pregnancy rate， spontaneous miscarriage rate， ectopic pregnancy rate， twin delivery rate， premature delivery rate and newborn weight among the three groups （P>0.05）. Logistic regression analysis revealed that the three luteal support regimens did not affect live birth rate. Pharmacoeconomic analysis showed that taking group B as a reference， the cost increased by 19 227.30 yuan for every 1% increase in live birth rate in group A. ConclusionsIn NC-FET cycle， oral dydrogesterone alone can achieve the same clinical outcomes as vaginal progesterone soft capsules and vaginal progesterone soft capsules combined with dydrogesterone. Compared with that of progesterone soft capsules， the cost of oral dydrogesterone alone is increased， a large sample and multicenter prospective study is needed to further confirm our results.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study / 中国结合医学杂志

OBJECTIVE@#To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated.@*METHODS@#A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay.@*RESULTS@#Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05).@*CONCLUSIONS@#ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

Effect of Insemination Methods on Pregnancy Outcomes of Day 6 Blastocyst Transfer in Frozen Cycles / 中山大学学报(医学科学版)

ObjectiveTo compare the effects of two different insemination methods， conventional in vitro fertilization （IVF） and intracytoplasmic sperm injection （ICSI）， on pregnancy outcomes in patients with frozen-thawed D6（day 6） blastocyst transfer. MethodsA retrospective cohort study was conducted to analyze the clinical data of patients with thawed D6 blastocyst transfer between January 2018 and April 2020 at the Fertility Center of the Third Hospital of Sun Yat-sen University， divided into conventional IVF group （446 cycles ） and ICSI fertilization group （200 cycles） according to the fertilization method. Patients were divided into those with a history of D5（day 5） blastocyst transfer and those without. The patients’ general characteristics， blastocyst quality， and pregnancy outcomes of the two groups were compared. ResultsBMI， years of infertility， and basal FSH were not statistically significant in the IVF and ICSI groups （P > 0.05）. Regardless of the history of D5 transfer， patients in the ICSI group were younger than those in the IVF group （P < 0.001）， the proportion of primary infertility was significantly higher in the ICSI group （P < 0.001）， and the number of oocytes obtained and the number of normally fertilized oocytes in the ICSI group were higher than those in the conventional IVF fertilization group （P < 0.001）. The proportion of stage V and Ⅵ blastocysts was significantly higher in the conventional IVF group than in the ICSI group （21.6 % vs. 3.14 %， P < 0.001）. High-quality blastocysts with an ICM score of A were significantly higher in the ICSI group than in the IVF group （23.8 % vs. 14.3 %， P = 0.01）. The HCG-positive and clinical pregnancy rates were significantly higher in the ICSI group than in the IVF group （65.5 % vs. 48.4 %， P < 0.001； 56 % vs. 41.3 %， P = 0.001）， and embryo implantation and live birth rates were also higher in the ICSI group than in the conventional IVF group （43.8 % vs. 30.9 %， P < 0.001； 43.0 % vs. 31.8 %， P = 0.006）. After correcting for age and number of oocytes obtained between the two groups， the clinical pregnancy rate was still significantly higher in the ICSI group than in the conventional IVF group （OR： 1.590， 95 % CI： 1.030， 2.455， P = 0.036）. Infant birth weight was lower in the ICSI group than in the IVF group （P = 0.016）， and the differences in preterm birth rate， sex ratio， and mode of delivery were not statistically significant between the two groups. ConclusionsClinical pregnancy and live birth rates after thawing and transfer of D6 blastocysts fertilized by ICSI are higher than those of D6 blastocysts fertilized by conventional IVF， which may be related to the different factors contributing to the slow development of blastocysts in patients who received different fertilization methods. The relatively good pregnancy outcome after the transfer of thawed D6 blastocysts fertilized by ICSI may compensate to some extent for the difference in pregnancy outcome due to the relatively slow blastocyst development and a relatively higher proportion of D6 blastocysts after ICSI fertilization in male infertility patients.

Advances in the Effects of Antiphospholipid Syndrome on Female Infertility and Outcomes of Assisted Reproductive Technologies / 中山大学学报(医学科学版)

Antiphospholipid syndrome （APS） is an autoimmune disease characterized by the persistent presence of antiphospholipid antibodies， which are associated with thrombosis and pregnancy-related complications. APS may have adverse effects on female reproductive function by affecting ovarian function， endometrialization， and other mechanisms， and may lead to embryo implantation failure and pregnancy loss during in vitro fertilization and embryo transfer （IVF-ET） treatments. The routine screening and management of APS before IVF-ET in infertile populations remains controversial and requires individualized risk assessment and appropriate management measures to improve the success rate of assisted reproductive technologies （ART） and reduce maternal and fetal risks during pregnancy. This review summarizes the effects of APS on female infertility and outcomes of ART， as well as the management of the population affected by APS， providing new insights for clinical diagnosis and treatment.

Correlation Between Blastocyst Morphology Score， Early Serum β-hCG Concentrations and Live Birth After Thawed Single Blastocyst Transfer / 中山大学学报(医学科学版)

ObjectivesTo assess the correlation between blastocyst morphology score， serum human chorionic gonadotropin β subunit （β-hCG） levels on day 12 after transfer and live birth outcomes among cycles tested HCG-positive after thawed single blastocyst transfer； to analyze the predictive value of serum β-hCG levels on live birth. MethodsWe reviewed the data of 519 frozen-thawed single blastocyst transfer cycles （FET） that had been tested HCG-positive from January 2016 to May 2020 at our IVF center. These FET cycles were firstly divided into 4 groups （AA， AB， BA， and BB） according to Gardner's grading system of inner cell mass （ICM） and trophectoderm cell （TE）， and then 4 groups （stages 3， 4， 5 and 6） according to the degree of blastocyst expansion. Serum β-hCG concentrations on day 12 after transfer and live birth rates were compared among groups transferred with different blastocysts grading and expansion stage. The relationship between Gardner’s grading or expansion stage of blastocysts and serum β-hCG levels was determined by correlation test， and ROC curves were plotted to determine the threshold values of serum β-hCG for predicting live birth. Results（1） The serum β-hCG concentration in the AA group and AB group on the 12th day after the transfer was significantly higher than that in the BB group （P <0.001， P <0.001）. However， there was no significant difference in the live birth rate when different ICM/TE-graded blastocysts were transferred （P = 0.120）. There were no significant differences in serum β-hCG concentration on day 12 after transfer and live birth rate among blastocysts with different expansion stages （P = 0.091， P = 0.557）. （2） There was a significant weak correlation between blastocyst ICM/TE grading and serum β-hCG concentration on day 12 （rs = -0.221， P <0.001）， and even after controlling for confounding factors （ rs = -0.228， P <0.001）；There was no significant correlation between blastocyst’s expansion stage and serum β-hCG concentration on day 12 after the transfer （rs = -0.052， P = 0.240）， and the association remained insignificant after controlling for confounding factors （rs = -0.029， P = 0.508）. （3） ROC curve analysis showed that the cut-off value for predicting live birth by serum β-hCG on day 12 was 657.5 mU/mL （P < 0.001）. ConclusionsNeither the ICM/TE grade nor the expansion stage of blastocysts affect the live birth rate，there is significant difference in the level of β-hCG produced by blastocyst with different ICM/TE grade；Our results suggest that early serum β-hCG level can predict live birth.

Mitochondrial Function Reveals Connotation of "Seven-Seven" Theory of Huangdi's Internal Classic and Mechanism of Herbal Intervention for Elderly Women Undergoing IVF-ET / 中国实验方剂学杂志

ObjectiveTo study the changes of mitochondrial function of ovarian granulosa cells in women of different ages and the effect of Erzhi-Tiangui prescription on in vitro fertilization-embryo transfer （IVF-ET） outcomes for elderly women， so as to verify the connotation of the "Seven-Seven" theory in the Huangdi's Internal Classic （《黄帝内经》）. MethodA total of 150 infertility patients undergoing IVF-ET at the Reproductive and Genetic Center of Integrative Medicine， Affiliated Hospital of Shandong University of Traditional Chinese Medicine were recruited and assigned into "hree-Seven/Four-Seven （30 cases）， Five-Seven （60 cases）， and Six-Seven （60 cases） groups according to the "Seven-Seven" theory. The Five-Seven and Six-Seven groups were further assigned into control and Chinese medicine subgroups using the random number plus envelope method， and the Chinese medicine group was administrated with Erzhi Tiangui prescription from the start day of controlled ovulation stimulation cycle to the trigger day. The IVF outcome was observed， and Western blot was employed to determine the levels of mitofusin 1 （MFN1）， mitofusin 2 （MFN2）， and dynamin-related protein 1 （Drp1） in the ovarian granulosa cells. ResultCompared with the Three-Seven/Four-Seven group， the control subgroups of the Five-Seven and Six-Seven groups showed decreased retrieved oocytes， two pronuclear （2PN） embryos， available embryos， high-quality embryos， clinical pregnancy rate， and live birth rate （P<0.05）. Moreover， the control subgroup of the Six-Seven group showed decreased fresh embryo transfer rate（P<0.05）. Compared with the control subgroup of the Five-Seven group， that of the Six-Seven group showed reduced retrieved oocytes， 2PN embryos， available embryos， high-quality embryos， and clinical pregnancy rate （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， 2PN oocytes， and available embryos than the control subgroup in the Five-Seven groups （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， than the control subgroup in the Six-Seven groups （P<0.05）. The control subgroup of the Six-Seven group showed lower expression levels of Mfn1 and Mfn2 and higher level of Drp1 than the control subgroup of the Five-Seven group （P<0.05）， which indicated that the levels of Mfn1 and Mfn2 in ovarian granulosa cells were down-regulated while the expression of Drp1 was up-regulated with aging （P<0.05）. The Chinese medicine subgroup had higher Mfn2 level and lower Drp1 level than the control subgroup in the Five-Seven group （P<0.05）， and the Chinese medicine subgroup had higher Mfn1 and Mfn2 levels and lower Drp1 level than then control subgroup in the Six-Seven group （P<0.05）. ConclusionsThe prognosis of IVF in women after "Five-Seven" became worse with aging， and the mitochondria in ovarian granulosa cells showed decreased fusion ability and increased fission， which verified the connotation of the "Seven-Seven" theory from the mitochondrial function. Erzhi Tiangui prescription can regulate the mitochondrial function of ovarian granulosa cells in elderly women， up-regulate the expression levels of Mfn1 and Mfn2 to promote mitochondrial fusion， and down-regulate the expression of Drp1 to reduce mitochondrial fission， thus alleviating the ovarian hypofunction caused by aging， improve the development potential of oocytes， and improve the IVF outcomes of elderly women. However， this prescription has limited efficacy for the elderly women in the age range of "Six-Seven".

Effects of paternal age on pregnancy outcomes in frozen-thaw embryo transfer cycles / 现代泌尿外科杂志

【Objective】 To observe the effects of paternal age on the pregnancy outcomes in frozen embryo transfer (FET) cycles. 【Methods】 The clinical data of two groups after propensity score matching (PSM) were retrospectively analyzed, including 738 cycles in the 0.05). The clinical pregnancy rate (52.2%vs. 67.2%) and live birth rate (41.1% vs. 57.2%) decreased in the 40-60 year group compared with those in the 0.05). 【Conclusion】 Advanced paternal age decreases clinical pregnancy rate and live birth rate.

Effect of follicular size on clinical outcomes of frozen-thawed embryo transfer induced by hCG on ovulation in natural cycles / 中华妇产科杂志

Objective:To investigate the effect of follicular size on the clinical outcomes of frozen-thawed embryo transfer induced by human chorionic gonadotropin (hCG) of natural cycles on ovulation.Methods:Clinical data of 427 cycles of frozen-thawed single blastocyst transfer in Nanjing Drum Tower Hospital from January 2016 to December 2019 were retrospectively analyzed. The patients were divided into 15-16 mm group (15≤diameter≤16 mm, n=66), 16-17 mm group (16<diameter≤17 mm, n=101), 17-18 mm group (17<diameter≤18 mm, n=125), 18-20 mm group (18<diameter≤20 mm, n=109),>20 mm group (diameter>20 mm, n=26), according to the maximum follicle diameter on the induction day of hCG ovulation induction. The estradiol and luteinizing hormone (LH) levels, and clinical pregnancy rate, abortion rate and live birth rate were compared in five groups. Results:There were statistically significant differences in estradiol and LH levels among the five groups on the day of hCG induction (all P<0.05). Estradiol levels in 15-16 mm group to >20 mm group gradually increased on the day of hCG induction, and estradiol level in 15-16 mm group was significantly lower than those in 17-18 mm group, 18-20 mm group and >20 mm group (median: 1 002.3 vs 1 103.3 vs 1 171.2 vs 1 539.0 pmol/L), with statistical significances ( P=0.034, P<0.001, P=0.002). On the day of hCG induction, LH levels in 15-16 mm group to >20 mm group showed a decreasing trend, and LH level in 15-16 mm group was significantly higher than those in 17-18 mm group and >20 mm group (median: 37.73 vs 28.24 vs 24.11 U/L), with statistically significant differences ( P=0.007, P=0.006). There were no significant differences in clinical pregnancy rate, abortion rate and live birth rate in 15-16 mm group to >20 mm group (all P>0.05). Conclusion:In the natural cycle protocol of hCG induced ovulation, the small follicle group could achieve similar clinical outcomes compared with normal sized follicles in the single blastocyst transfer of frozen-thawed embryos.

Analysis of reproductive outcomes in the first IVF-ET cycle after laparoscopic treatment in patients with endometriosis / 中华妇产科杂志

Objective:To explore the effect of endometriosis (EM) on reproductive outcomes of young patient with EM after laparoscopic treatment in the first in vitro fertilization-embryo transfer (IVF-ET) cycle.Methods:The clinical data and reproductive outcomes of 394 infertile patients with EM after laparoscopic treatment (EM group) and 3 242 infertile patients caused by gamete transport disorder (control group) in the first IVF-ET cycle were collected in Chongqing Health Center for Women and Children from January 2016 to June 2021. The information included baseline characteristics, oocyte retrieval, embryo development, clinical pregnancy, miscarriage, and live birth. Propensity score matching (PSM) method was used to perform 1∶2 matching between EM group and control group. The impact of EM on reproductive outcomes was analyzed in the retrospective observational study.Results:In the initial data, compared with control group, the number of two pronucleus (2PN) zygotes (9.7±4.8 vs 9.0±4.4), the number of transferable embryos (6.2±3.6 vs 5.5±3.4) and the rate of transferable embryos (64.0% vs 60.8%) on the third day were significantly lower in EM group, and the differences were statistically significant (all P<0.05). After PSM was performed, there were 394 and 787 cases in EM group and control group, respectively. Compared with control group, the number of 2PN zygotes (9.7±4.9 vs 9.0±4.4), the 2PN fertility rate (77.1% vs 75.3%), the number of transferable embryos on the third day (6.2±3.6 vs 5.5±3.4), the transferable embryos rate on the third day (63.8% vs 60.8%) were significantly lower in EM group, and the differences were statically significant (all P<0.05). The study did not find the effect of EM on embryo implantation rate, pregnancy rate, early miscarriage rate, live birth rate and preterm birth rate (all P>0.05). Conclusions:EM might interfere with the development of oocytes and embryos. Obtaining top-quality embryos may be an effective way to improve the prognosis of patients with EM after laparoscopic treatment.

Determination of endometrial receptivity by three-dimensional power ultrasound for evaluation of pregnancy outcome after in vitro fertilization and embryo transfer / 中国基层医药

Objective:To investigate the clinical value of endometrial receptivity determination by transvaginal three-dimensional power ultrasound in the prediction of pregnancy outcome after in vitro fertilization and embryo transfer. Methods:A total of 220 infertile patients who underwent in vitro fertilization and embryo transfer in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from July 2018 to July 2021 were included in this study. Before in vitro fertilization and embryo transfer, all patients were tested for endometrial receptivity by transvaginal two-dimensional and three-dimensional power ultrasound. Pregnancy outcomes were followed up. Anatomical indexes (endometrial thickness, endometrial volume, and endometrial morphology) and endometrial blood flow indexes [endometrial blood flow type, pulsation index, resistance index (RI), ratio of peak systolic velocity to end-diastolic velocity (S/D), vascularization index (Vl), blood flow index (FI) and vascular blood flow index (VFI)] were compared between different pregnancy outcomes. Results:There were no significant differences in endometrial thickness, endometrial volume, and endometrial morphology between successful pregnancy and failed pregnancy groups ( t or χ2 = 0.23-0.54, P = 0.523-0.890). There was no significant difference in endometrial blood flow typing between successful pregnancy and failed pregnancy groups ( χ2 = 0.217, P = 0.897). PI, RI, and S/D in the successful pregnancy group were (2.46 ± 0.29), (1.07 ± 0.21), and (0.57 ± 0.10), respectively, which were significantly lower than (2.71 ± 0.34), (1.35 ± 0.24), and (0.66 ± 0.11) in the failed pregnancy group ( t = 4.51, 5.27, 3.43, all P < 0.001). VI, FI, and VFI values in the successful pregnancy group were (23.04 ± 2.95), (32.26 ± 3.17), and (6.59 ± 0.94) respectively, which were significantly higher than (16.85 ± 2.17), (28.42 ± 3.04), and (4.88 ± 0.86) in the failed pregnancy group ( t = 10.94, 6.25, 8.37; all P < 0.001). Conclusion:Endometrial blood flow parameters such as PI, RI, S/D, VI, FI, and VFI determined by transvaginal three-dimensional power ultrasound have a certain predictive value for pregnancy outcomes after in vitro fertilization and embryo transfer. They can be used as sensitive indexes for evaluating endometrial receptivity.

Comparison of the Effects of GMCSF-Containing and Traditional Culture Media on Embryo Development and Pregnancy Success Rates

Abstract Objective The use of granulocyte macrophage colony-stimulating factor (GM-CSF)-containing medium, which is a commercial medium that is used for cultivation of embryos in in vitro fertilization (IVF) treatments, has been suggested to increase the efficiency of this procedure in patients with previous multiple unsuccessful attempts. In this retrospective study, we analyzed GM-CSF-containing embryo culture media compared with traditional culture media in terms of development of embryos, pregnancy, and ongoing pregnancy success and live birth rates. Methods This is a prospective case control study conducted in a single center. A total of 131 unexplained infertility patients were included in the study. A cohort of 69 patients whose embryos were cultured in GM-CSF-containing medium and a control group of 62 age-matched patients whose embryos were cultured in conventional Sage One Step medium were included in the study. The major study outcomes were achievement of pregnancy and ongoing pregnancy rate at 12 weeks of gestation. Results The pregnancy and ongoing pregnancy rates of the patients whose embryos were cultured in GM-CSF-containing medium were 39.13% and 36.23%, respectively. These were higher than the rates of the control group, which were 30.65% and 29.03%, respectively, although this difference was not statistically significant. In addition, the 5th-day embryo transfer percentage in the GM-CSF group was higher than in the control group (34.78% versus 27.4%). Conclusion The main findings of our study were that there was no difference between the GM-CSF-enhanced medium and the control group in terms of our major study outcomes. However, blastomere inequality rate and embryo fragmentation rates were lower in the GM-CSF group.

The Addition of Dydrogesterone after Frozen Embryo Transfer in Hormonal Substituted Cycles with Low Progesterone Levels / Uso adicional de didrogesterona após transferência de blastocisto em ciclos substituídos com valores baixos de progesterona

Abstract Objective To determine whether a rescue strategy using dydrogesterone (DYD) could improve the outcomes of frozen embryo transfer cycles (FET) with low progesterone (P4) levels on the day of a blastocyst transfer. Methods Retrospective cohort study including FET cycles performed between July 2019 and October 2020 following an artificial endometrial preparation cycle using estradiol valerate and micronized vaginal P4 (400 mg twice daily). Whenever the serum P4 value was below 10 ng/mL on the morning of the planned transfer, DYD 10 mg three times a day was added as supplementation. The primary endpoint was ongoing pregnancy beyond 10 weeks. The sample was subdivided into two groups according to serum P4 on the day of FET: low (< 10 ng/mL, with DYD supplementation) or normal (above 10 ng/mL). We performed linear or logistic generalized estimating equations (GEE), as appropriate. Results We analyzed 304 FET cycles from 241 couples, 11.8% (n = 36) of which had serum P4 below 10 ng/mL on the FET day. Baseline clinical data of patients was comparable between the study groups. Overall, 191 cycles (62.8%) had a biochemical pregnancy, of which 131 (44,1%) were ongoing pregnancies, with a 29,8% miscarriage rate. We found no statistically significant differences in the hCG positive (63 vs 64%) or ongoing pregnancy rates (50 vs 43,3%) between those FETs with low or normal serum P4 values, even after multivariable logistic regression modelling. Conclusion Our results indicate that DYD 10 mg three times a day administered in women who perform FET with P4 serum levels < 10 ng/mL, allows this group to have pregnancy rates beyond 12 weeks at least as good as those with serum levels above 10 ng/mL.

Resumo Objetivo Determinar se uma estratégia de resgate usando didrogesterona (DYD) pode melhorar os resultados dos ciclos de transferência de embriões congelados (TEC) com baixos níveis de progesterona (P4) no dia de uma transferência de blastocisto. Métodos Estudo de coorte retrospectivo que incluiu ciclos TEC realizados entre julho de 2019 e outubro de 2020 após um ciclo de preparação endometrial artificial usando valerato de estradiol e P4 vaginal micronizado (400 mg duas vezes ao dia). Sempre que o valor de P4 sérico estava abaixo de 10 ng/mL na manhã da transferência planejada, adicionou-se 10 mg de DYD tri-diário como suplementação. O desfecho primário foi gravidez evolutiva após 10 semanas. A amostra foi subdividida em dois grupos de acordo com o P4 sérico no dia da TEC: baixo (< 10 ng/mL, com suplementação de DYD) ou normal (acima de 10 ng/mL). Realizamos equações de estimativa generalizada linear ou logística (GEE), conforme apropriado. Resultados Analisaram-se 304 ciclos de FET de 241 casais, dos quais 11,8% (n = 36) tinham valores de P4 sérico abaixo de 10 ng/mL no dia da TEC. Os dados clínicos e demográficos dos pacientes eram comparáveis entre os grupos. Globalmente, 191 ciclos (62,8%) tiveram uma gravidez bioquímica, dos quais 131 (44,1%) foram gestações em curso, com uma taxa de aborto espontâneo de 29,8%. Não encontramos diferenças estatisticamente significativas na taxa de gravidez bioquímica (63 vs. 64%) ou nas taxas de gravidez evolutiva (50 vs. 43,3%) entre TEC com valores séricos de P4 baixos ou normais, mesmo após modelação com regressão logística multivariável. Conclusão Nossos resultados indicam que a suplementação com DYD 10 mg três vezes ao dia em mulheres com níveis séricos de P4 abaixo de 10 ng/mL em ciclos de TEC substituídos parecem conseguir resultados pelo menos tão bons como nos ciclos com valores superiores para taxas de gravidez em curso além de 12 semanas.

Asynchrony between in vivo and in vitro rabbit embryos

Background: Comparative features of embryos developed under in vitro and in vivo conditions are particularly important in designing embryo transfer procedures that fulfil embryo-recipient synchronization requirements. Objective: To determine the degree of asynchrony in rabbit embryo development between cultured and in vivo embryos. Methods: A total of 55 non- lactating multiparous female rabbits were used. Embryos were classified as 16-cells or early morulae at 48 hours post-coitum (hpc). Embryos were cultured during 30 or 32 h and embryo development was compared with in vivo embryos of 72 hpc. In vitro and in vivo embryos at 72 hpc were classified as early or compacted morulae. Bayesian statistics was used. Difference between in vivo and in vitro embryos and the actual probability of the difference between the in vivo and in vitro embryo higher than zero (P) was estimated. Results: The percentage of compacted morulae was higher in in vivo embryos than in in vitro embryos with +6 h of asynchrony (73.5 and 32.8%, P=1.00). But the percentage of compacted morulae was similar with +8 h asynchrony. Conclusions: In vitro embryos delay their development by + 8 hours compared to in vivo embryos.

Antecedentes: El desarrollo comparativo de embriones producidos in vitro e in vivo es particularmente importante para el diseño de procedimientos de transferencia de embriones cuando se requiere sincronización entre el embrión y la hembra receptora. Objetivo: Determinar el grado de asincronía en el desarrollo embrionario entre embriones in vivo y cultivados. Métodos: Un total de 55 conejas multiparas no lactantes fueron utilizadas. Los embriones se clasificaron en 16 células o mórulas tempranas a las 48 horas después del coito (hpc). Los embriones se cultivaron durante 30 ó 32 horas y el desarrollo embrionario se comparó con embriones de 72 hpc obtenidos in vivo. Los embriones in vitro e in vivo a 72 hpc se clasificaron como mórulas tempranas o compactas. Se utilizó estadística bayesiana. Se estimó la diferencia entre embriones in vivo e in vitro y la probabilidad de que la diferencia sea superior a cero (P). Resultados: El porcentaje de mórulas compactas fue mayor en embriones in vivo que en embriones in vitro con +6 horas de asincronía (73,5 y 32,8%, P=1,00), pero el porcentaje de mórulas compactas fue similar con asincronía de +8 horas. Conclusión: Los embriones cultivados retrasan +8 horas su desarrollo en comparación con los embriones in vivo.

Antecedentes: A aquisição do desenvolvimento de embriões produzidos in vitro e in vivo é particularmente importante na concepção de procedimentos de transferência de embriões em que a sincronização entre o embrião e a fêmea receptora é necessária. Objetivo: Determinar o grau de assincronia no desenvolvimento embrionário entre embriões cultivados e in vivo. Métodos: Um total de 55 coelhos multíparos não lactantes foram usados. Os embriões foram classificados em 16 células ou mórulas iniciais 48 horas de gestação (hpc). Os embriões foram cultivados por 30 ou 32 horas e o desenvolvimento embrionário foi comparado com embriões de 72 hpc obtidos in vivo. Embriões in vitro e in vivo a 72 hpc foram classificados como mórulas precoces ou compactadas. Estatísticas bayesianas foram usadas. A diferença entre embriões in vivo e in vitro e a probabilidade de que a diferença seja maior que zero (P) foi estimada. Resultados: A porcentagem de mórulas compactadas foi maior em embriões in vivo do que em embriões in vitro com +6 horas de assincronia (73,5 e 32,8%, P=1,00). Mas a porcentagem de mórulas compactadas foi semelhante com assincronia de +8 horas. Conclusão: Embriões cultivados atrasam seu desenvolvimento em +8 horas em comparação com embriões in vivo.

One Plus One is Better than Two: An Approach Towards a Single Blastocyst Transfer Policy for All IVF Patients / Um mais um é melhor que dois: Uma abordagem pela prática da transferência de embrião único para todos os pacientes de FIV

Abstract Objective It is known that the single embryo transfer (SET) is the best choice to reduce multiples and associated risks. The practice of cryopreserving all embryos for posterior transfer has been increasingly performed for in vitro fertilization (IVF) patients at the risk of ovarian hyperstimulation syndrome or preimplantation genetic testing for aneuploidy. However, its widespread practice is still controverse. The aim of this study was to evaluate how effective is the transfer of two sequential SET procedures compared with a double embryo transfer (DET) in freeze-only cycles. Methods This retrospective study reviewed 5,156 IVF cycles performed between 2011 and 2019, and 506 cycles using own oocytes and freeze-only policy with subsequent elective frozen-thawed embryo transfers (eFET) were selected for this study. Cycles having elective SET (eSET, n = 209) comprised our study group and as control group we included cycles performed with elective DET (eDET, n = 291). In the eSET group, 57 couples who had failed in the 1st eSET had a 2nd eFET, and the estimated cumulative ongoing pregnancy rate was calculated and compared with eDET. Results After the 1st eFET, the ongoing pregnancy rates were similar between groups (eSET: 35.4% versus eDET: 38.5%; p =0.497), but the estimated cumulative ongoing pregnancy rate after a 2nd eFET in the eSET group (eSET + SET) was significantly higher (48.8%) than in the eDET group (p < 0.001). Additionally, the eSET +SET group had a 2.7% rate of multiple gestations, which is significantly lower than the eDET group, with a 30.4% rate (p < 0.001). Conclusion Our study showed the association of freeze-only strategy with until up to two consecutive frozen-thawed eSETs resulted in higher success rates than a frozenthawed DET, while drastically reducing the rate of multiple pregnancies.

Resumo Objetivo Sabe-se que a transferência de embrião único (SET) é a melhor escolha para reduzir as gestações múltiplas e riscos associados. A prática da criopreservação de todos os embriões para transferência posterior tem sido cada vez mais utilizada para fertilização in vitro (FIV), em especial quando há risco de síndrome de hiperestimulação ovariana ou realização de teste genético pré-implantacional. Entretanto, sua utilização disseminada ainda é controversa. O objetivo deste estudo foi avaliar a eficácia de duas SET sequenciais em comparação com uma transferência de embrião dupla (DET) em ciclos de FIV onde todos os embriões foram criopreservados. Métodos Neste estudo retrospectivo foram revisados 5.156 ciclos de FIV realizados entre 2011 e 2019, e 506 ciclos usando oócitos próprios e criopreservação de todos os embriões com transferências eletivas subsequentes de embriões descongelados, foram selecionados para este estudo. Ciclos com transferência eletiva de embrião único (eSET, n = 209) compuseram nosso grupo de estudo e como grupo de controle incluímos os ciclos com transferência eletiva de dois embriões (eDET, n = 291). No grupo eSET, 57 casais que falharam na 1ª tentativa de eSET tiveram uma 2ª eFET e a taxa de gravidez em curso cumulativa foi estimada para o grupo eSET e comparada com o grupo eDET. Resultados Após a 1ª eFET, as taxas de gravidez em curso foram semelhantes entre os grupos (eSET: 35,4% versus eDET: 38,5%; p = 0,497), mas a taxa de gravidez em curso cumulativa estimada após a 2ª eFET no grupo eSET (eSET + SET) foi significativamente maior (48,8%) do que no grupo eDET (p <0,001). Além disso, as taxas de gestação múltipla foram expressivamente inferiores no grupo eSET + SET (2,7%) quando comparado ao grupo eDET (30,4%; p < 0,001). Conclusão Nosso estudo mostrou que a associação das estratégias de congelamento de todos os embriões com até duas eSETs sequenciais resultou em maiores taxas de sucesso do que uma DET com embriões descongelados, além de reduzir drasticamente a ocorrência de gestações múltiplas.

Effect of autologous platelet-rich plasma treatment on patients with thin endometrium / Efecto del tratamiento con plasma autólogo rico en plaquetas en pacientes con endometrio delgado

ABSTRACT Introduction: The success of frozen embryo transfer cycles depends on a delicate interaction between embryo quality and endometrium. Low pregnancy rates are associated with a thin endometrium. Objective: To evaluate the effect of autologous platelet-rich plasma treatment on patients with thin endometrium. Methods: In 34 patients with thin endometrium (< 7 mm), canceled in the previous frozen embryo transfer cycles, autologous platelet-rich plasma was prepared, from autologous peripheral vein blood; intrauterine infusion was given during hormone replacement therapy in frozen embryo transfer cycles. Frozen embryo transfer was performed when the endometrium thickness reached ≥ 7mm. Results: Six patients canceled the embryo transfer cycle due to endometrium thickness did not reach 7 mm; 28 patients got endometrial thickness ≥ 7 mm and performed frozen embryo transfer. The endometrial thickness was 7.5 ± 0.8 mm, which was significantly thicker than in the previous cycles (5.6 ± 0.79 mm) with p< 0.002, the implantation rate was 23.07 %, and the clinical pregnancy rate was 12/28 (42.8 %). Conclusion: Autologous platelet-rich plasma improves the endometrial thickness and the pregnancy rate outcomes in women with thin endometrium.

RESUMEN Introducción: El éxito de los ciclos de transferencia de embriones congelados depende de una delicada interacción entre la calidad del embrión y el endometrio. Las bajas tasas de embarazo están asociadas con un endometrio delgado. Objetivo: Evaluar el efecto del tratamiento con plasma rico en plaquetas autólogo en pacientes con endometrial delgado. Métodos: En 34 pacientes con endometrio delgado (< 7 mm) canceladas en los ciclos previos de transferencia de embriones congelados, se preparó plasma autólogo rico en plaquetas, a partir de sangre autóloga de venas periféricas; la infusión intrauterina se administró durante la terapia de reemplazo hormonal en los ciclos de transferencia de embriones congelados. La transferencia de embriones congelados se realizó cuando el grosor del endometrio alcanzó ≥ 7 mm. Resultados: En 6s pacientes se canceló el ciclo de transferencia embrionaria debido a que el grosor del endometrio no alcanzó los 7 mm; 28 pacientes obtuvieron un grosor endometrial ≥ 7 mm y realizaron transferencia de embriones congelados. El grosor del endometrio fue de 7,5 ± 0,8 mm, significativamente mayor que en los ciclos anteriores (5,6 ± 0,79 mm) con p< 0,002; la tasa de implantación fue de 23,07 % y la tasa de embarazo clínico fue de 12/28 (42,8 %). Conclusión: El plasma autólogo rico en plaquetas mejora el grosor endometrial y los resultados de la tasa de embarazo en mujeres con endometrio delgado.

Is There Any Effect of the Physician Performing Embryo Transfer in IVF-ICSI Treatment: A Prospective Cohort Study / Existe algum efeito domédico que realiza a transferência de embriões no tratamento de FIV-ICSI: Um estudo de coorte prospectivo

Abstract Objective To evaluate whether there is an effect of the physician who transfers the embryos on pregnancy rates in in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) treatment. Methods A total of 757 participants were analyzed between 2012 and 2017. Participants were classified according to 3 physicians who transferred the embryos: ([group 1=164 patients]; [group 2=233 patients]; [group 3=360 patients]). Baseline parameters and IVF-ICSI outcomes were compared between the groups. Results No differences were determined between the groups regarding the baseline parameters (age, age subgroups [20-29, 30-39, and ≥ 40 years old)], body mass index (BMI), smoking status, infertility period, cause of infertility, baseline follicle stimulating hormone, luteinizing hormone, estradiol (E2), thyroid stimulating hormone, prolactin levels, antral follicle count, duration of stimulation, stimulation protocol, gonadotropin dose required, maximum E2 levels, progesterone levels, endometrial thickness on human chorionic gonadotropin (hCG) administration and transfer days (p>0.05). The numbers of oocytes retrieved,metaphase II (MII), 2 pronucleus (2PN), transferred embryo, fertilization rate, day ofembryo transfer, the catheter effect and embryo transfer technique, and clinical pregnancy rates (CPRs) were also comparable between the groups (p>0.05). Conclusion Our data suggests that the physician who transfers the embryos has no impact on CPRs in patients who have undergone IVF-ICSI, but further studies with more participants are required to elucidate this situation.

Resumo Objetivo Avaliar se há ou não efeito do médico que realiza a transferência de embriões nas taxas de gravidez no tratamento com fertilização in vitro-injeção intracitoplasmática de espermatozoide (FIV-ICSI, na sigla em inglês). Métodos Um total de 757 participantes foram analisados entre 2012 e 2017. Os participantes foram classificados de acordo com 3 médicos que transferiram os embriões: ([grupo 1=164 pacientes]; [grupo 2=233 pacientes]; [grupo 3=360 pacientes]). Parâmetros basais e resultados de FIV-ICSI foram comparados entre os grupos. Resultados Nenhuma diferença foi determinada entre os grupos nos parâmetros basais (idade, subgrupos de idade [20-29, 30-39 e ≥ 40 anos)], índice de massa corporal (IMC), tabagismo, período de infertilidade, causa da infertilidade, hormônio folículo estimulante basal , hormônio luteinizante, estradiol (E2), hormônio estimulador da tireoide, níveis de prolactina, contagem de folículos antrais, duração da estimulação, protocolo de estimulação, dose de gonadotrofina necessária, níveis máximos de E2, níveis de progesterona e espessura endometrial na administração de hCG e nos dias de transferência (p>0,05). O número de oócitos recuperados, MII e 2PN, embrião transferido, taxa de fertilização, dia da transferência do embrião, o efeito do cateter e a técnica de transferência de embrião e taxas clínicas de gravidez (RCPs) também foram comparáveis entre os grupos (p>0,05). Conclusão Nossos dados sugerem que o médico que transfere os embriões não tem impacto sobre as RCPs em pacientes que se submeteram a FIV-ICSI, mas mais estudos com mais participantes são necessários para elucidar esta situação.

Oral dydrogesterone in frozen-thawed embryo transfer cycles

SUMMARY OBJECTIVE: The aim of this study was to compare the use of micronized vaginal progesterone and oral dydrogesterone in the endometrial preparation for frozen-thawed embryo transfer. METHODS: This was a randomized, controlled, open, two-armed clinical trial, with women undergoing frozen-thawed embryo transfer along with hormone replacement therapy for endometrial preparation, between September 2019 and February 2021. A total of 73 patients were randomly selected and orally administered 40 mg/day dydrogesterone (dydrogesterone group, n=36) or 800 mg/day micronized vaginal progesterone (micronized vaginal progesterone group, n=37), after endometrial preparation with transdermal estradiol. The main outcome was a viable ongoing pregnancy with 12 weeks of gestation as evaluated by ultrasound. RESULTS: The reproductive outcomes in frozen-thawed embryo transfer cycles were similar, with pregnancy rates in the dydrogesterone and micronized vaginal progesterone treatment groups being, respectively, 33.3 and 32.4% at 12 weeks pregnancy (confidence interval= -22.4-20.6, p=0.196). CONCLUSIONS: The use of oral dydrogesterone may be a more patient-friendly approach to endometrial preparation in frozen-thawed embryo transfer cycles, avoiding undesirable side effects and discomfort resulting from vaginal administration, while also providing similar reproductive results.