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1.
Arch Gynecol Obstet ; 300(4): 1083-1092, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31529366

RESUMO

PURPOSE: To evaluate the impact of artificial oocyte activation (AOA) in pregnancy and neonatal outcomes in infertile patients undergoing cryopreserved embryo transfer. METHOD: This retrospective study included 5686 patients' transferred embryos from routine intracytoplasmic sperm injection (ICSI) and 194 patients' transferred embryos from ICSI combined with AOA (ICSI-AOA) from January 2011 to December 2016. Pregnancy and neonatal outcomes of couples undergoing routine ICSI or ICSI-AOA were analyzed before and after propensity score matching. Artificial oocyte activation was performed with ionomycin. RESULTS: The pregnancy outcomes showed no significant difference in the rates of biochemical pregnancy, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, multiple pregnancy, and live births between the routine ICSI and ICSI-AOA groups before and after propensity score matching, respectively. The assessment of neonatal outcomes showed no statistically significant differences in the birth defect rate, birth weight, gestational age, preterm birth rate, early-neonatal death rate, and fetal sex ratio between the two groups, and similar results were also observed in the two matched cohorts. CONCLUSION: Artificial oocyte activation with ionomycin does not adversely affect pregnancy and neonatal outcomes in patients undergoing frozen-thawed embryo transfer, which is beneficial to clinicians counseling patients on the risks of artificial oocyte activation.

2.
Drug Des Devel Ther ; 13: 2553-2563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440037

RESUMO

Purpose: Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear. Patients and methods: This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors. Results: In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40-2.39) and 0.90 (95% CI: 0.33-2.41) in singletons and twins, respectively. Conclusion: Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31393569

RESUMO

CONTEXT: The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is mainly expressed in gonads and plays important roles in estradiol production, ovulation and luteal formation. Women with pathogenic LHCGR variants suffer from infertility, and successful fertility treatments for such women have never been reported. OBJECTIVE: The purpose of this study was to determine whether women with pathogenic LHCGR variants can achieve successful pregnancies through in vitro fertilization (IVF). METHOD: Three women with luteinizing hormone (LH) resistance and infertility and their parents underwent exome sequencing. The biochemical characteristics and functional effects of LHCGR mutation were assessed in transfected HEK-293T cells and primary granulosa cells. RESULTS: All affected women harbored pathogenic LHCGR variants. The LHCGR variants lacked cell surface localization and signal transduction abilities in vitro and in vivo. After dual triggering and prolonging the interval between triggering and oocyte pick-up (OPU), all 3 patients achieved oocytes and high-quality embryos. After frozen embryo transfer, one woman successfully birthed twins, and one woman successfully birthed a live boy. Apart from difficulties in oocyte retrieval, no obvious abnormalities in fertilization or during embryo development and pregnancy were identified in these patients. CONCLUSIONS: This study is the first to report successful assisted reproductive treatment for women with pathogenic LHCGR variants using their own oocytes. Our results supported that defects in LHCGR disrupt ovulation but have no effect on fertilization and embryo development.

4.
Hum Reprod ; 34(9): 1707-1715, 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31398256

RESUMO

STUDY QUESTION: Does endometrial thickness (EMT) have an impact on singleton birthweight in frozen embryo transfer (FET) cycles? SUMMARY ANSWER: An EMT <8 mm was associated with a lower mean birthweight and gestational age- and gender-adjusted birthweight (Z-scores) of singletons resulting from FET. WHAT IS KNOWN ALREADY: Previous studies have examined the impact of EMT on IVF success rates. Little is known, however, regarding the relationship between EMT and neonatal birthweight. STUDY DESIGN, SIZE, DURATION: This retrospective study involved singleton live births born to women undergoing frozen-thawed Day 3 embryo transfer during the period from January 2010 to December 2017 at a tertiary care centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 6181 women who fulfilled the inclusion criteria were included and were grouped into five groups depending on the EMT: <8 mm, 8-9.9 mm, 10-11.9 mm, 12-13.9 mm and ≥14 mm. EMT between 10 and 11.9 mm was taken as a reference group. Singleton birthweight was the primary outcome measure. A multivariable linear regression analysis was performed to detect a relationship between EMT and newborns' birthweight after controlling for a number of potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: A modest but significant decrease in birthweight was observed in the EMT <8 mm group as compared with groups with EMT ≥10 mm, with a mean difference of 89-108 g. Also, singletons from the EMT <8 mm group (0.24 ± 1.04) had a significantly lower birthweight Z-scores than those from the EMT 10-11.9 mm (0.41 ± 1.02; P = 0.032) or EMT 12-13.9 mm (0.46 ± 1.07; P = 0.004) groups. Further, multiple linear regression analyses indicated that parental BMIs, gestational age, newborn gender, pregnancy complications and EMT <8 mm were all independent predictors of neonatal birthweight. LIMITATIONS, REASONS FOR CAUTION: The present study was limited by its retrospective design. Future prospective studies are required to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provided new insight into the relationship between EMT and neonatal outcomes by showing that a thin endometrium is associated with a decrease in singleton birthweight. STUDY FUNDING/COMPETING INTEREST(S): National Key Research and Development Program of China (2018YFC1003000); the National Natural Science Foundation of China (81771533, 81571397, 31770989, 81671520); the China Postdoctoral Science Foundation (2018M630456). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

5.
Fertil Steril ; 112(3): 527-533, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31272721

RESUMO

OBJECTIVE: To evaluate the outcomes of embryo transfer with the use of monopronuclear (1PN) zygotes, and the risks of congenital malformations and postpartum developmental disorders. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENT(S): This study included patients who underwent single embryo transfer of 1PN frozen-thawed cleavage- or blastocyst-stage embryos. Seventy-six singletons were assessed for congenital malformations and defects in psychomotor development. INTERVENTION(S): Monopronuclear frozen-thawed cleavage-stage or blastocyst embryos were compared with 2PN frozen-thawed cleavage-stage and blastocyst frozen embryos, in frozen-thawed embryo transfer (FET) cycles. Neonates from 2PN FET constituted the control group. MAIN OUTCOME MEASURE(S): Implantation rate (IR), clinical pregnancy rate (PR), miscarriage rate, live birth rate, congenital malformations, and motor and language development status were compared. RESULT(S): The cohort comprised 186, 676, 133, and 502 patients consenting to FET with, respectively, 1PN cleavage-stage, 2PN cleavage-stage, 1PN blastocystocyst, and 2PN blastocystocyst embryos. The IR, PR, and live birth rate were lower in 1PN than with 2PN cleavage-stage FET, but similar between 1PN and 2PN blastocystocysts. Miscarriage rates did not differ significantly between 1PN and 2PN cleavage-stage or blastocystocyst FET. Risk of congenital malformations and defects in psychomotor development did not differ significantly within 2 years postpartum with the use of 1PN or 2PN FET. CONCLUSION(S): The present results suggest that the value of 1PN blastocyst FET is similar to that of 2PN blastocyst FET, without an increased risk of miscarriage rate, congenital malformations, or defects of psychomotor development.

6.
BMC Med ; 17(1): 114, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31238940

RESUMO

BACKGROUND: Abnormal BMI is associated with discouraging IVF outcomes in fresh autologous or oocyte donor cycles, whether or not such a relation also holds true for women undergoing frozen-thawed embryo transfer (FET) remains unknown. In addition, it remains unclear the detrimental effect of abnormal BMI on IVF outcomes occurs at the level of ovary or endometrium. METHODS: A retrospective study involved 22,043 first FET cycles of all women who had undergone a freeze-all policy during the period from January 2010 to June 2017. To control for the embryo factor, our analysis was restricted to women with high-quality embryo transfer. The main outcome measure was live birth rate per embryo transfer. The secondary endpoints included rates of implantation, clinical pregnancy, multiple pregnancy, and pregnancy loss. Multivariate logistic regression analysis was performed to detect the independent effect of BMI on live birth rate after adjusting for important confounding variables. RESULTS: In the crude analysis, reproductive outcomes were similar between underweight women and normal-weight controls whereas all parameter outcomes were significantly worse in patients with obesity. After adjustment for a number of confounding factors, underweight women had a marginally significant decrease in rates of implantation (adjusted odds ratio (aOR) 0.91; 95% CI 0.85-0.96), clinical pregnancy (aOR 0.91; 95% CI 0.83-0.99), and live birth (aOR 0.91; 95% CI 0.83-0.99) as compared to the women with normal weight. Obesity was significantly associated with decreased implantation (aOR 0.80; 95% CI 0.73-0.87), clinical pregnancy (aOR 0.81; 95% CI 0.71-0.91), and live birth rates (aOR 0.70; 95% CI 0.62-0.80). Moreover, the pregnancy loss rate, both in the first (aOR 1.46; 95% CI 1.15-1.87) and in the second trimester (aOR 2.76; 95% CI 1.67-4.58), was significantly higher in the obesity group than that in the reference group. CONCLUSIONS: Among women undergoing first FET with high-quality embryo transfer, low BMI has limited impact on pregnancy and live birth rates. On the contrary, obesity was associated with worse IVF outcomes. Our findings further highlighted that endometrial receptivity played an important role in the poor reproductive outcomes of women with abnormal weight status.

8.
Reprod Biomed Online ; 39(1): 111-118, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109894

RESUMO

RESEARCH QUESTION: Does the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) improve the ongoing pregnancy rate of vitrified-warmed embryo transfer in women with adenomyosis undergoing IVF? DESIGN: This retrospective study included 358 women with adenomyosis undergoing IVF. Of these, 134 women were enrolled in the LNG-IUS group and another 224 women were in the control group. All women were screened for adenomyosis by transvaginal ultrasound and magnetic resonance imaging (MRI). There was no significant difference in the ages of women, FSH, cause of infertility, body mass index, total dose of gonadotrophin used and number of oocytes collected between the two groups. All comparisons performed were between patients undergoing vitrified-warmed embryo transfer. RESULTS: Statistical differences were found in the ongoing pregnancy rates (41.8% vs 29.5%, P = 0.017) between the LNG-IUS group and control group. Logistic regression analysis showed that the odds ratio (OR) of ongoing pregnancy was significantly increased with LNG-IUS usage (adjusted OR = 1.628, 95% confidence interval 1.011-2.622). Also, differences were found in implantation rates (32.1% vs 22.1%, P = 0.005) and clinical pregnancy rates (44% versus 33.5%, P = 0.045) between the LNG-IUS group and control group. CONCLUSIONS: The results of this study offer some support for evaluating the effect of pretreatment with LNG-IUS in women with adenomyosis in future randomized controlled trials.

9.
Horm Metab Res ; 51(5): 315-325, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31071736

RESUMO

BACKGROUND: The objective of the work was to investigate the cycle characteristics and outcomes of infertile women with nonclassic 21-hydroxylase deficiency (21-OHD) undergoing in vitro fertilization (IVF). METHODS: Twenty-five infertile nonclassic 21-OHD patients were retrospectively observed. From cycle day 3, patients were given human menopausal gonadotropin (HMG) 150 IU/d or 225 IU/d daily. Dexamethasone was administered orally at 0.75 mg/d. Ovulation was co-triggered by human chorionic gonadotropin (hCG) and triptorelin. Binary logistic regression was performed to quantify the effect of IVF parameters on embryo transfer cycle outcomes. The receiver operating characteristic (ROC) curve was used to determine cutoff points of the selected confounders for predicting pregnant probabilities. RESULTS: In controlled ovarian hyperstimulation (COH) cycles, there was a trend that the viable embryos group consisted of more polycystic ovary (PCO) patients. In embryo transfer (ET) cycles, differences were detected in the usage rate of dexamethasone and the minimum progesterone (P4) and total testosterone (TT) values between the non-pregnant group and the biochemical pregnant group. Binary logistic regression analysis confirmed that decreasing minimum P4 and body mass index (BMI) value was respectively correlated with increasing pregnancy probability. ROC analysis proved that the cutoff values for minimum P4 and BMI were 0.45 ng/ml and 23.36 kg/m2. CONCLUSION: In COH cycles, the ultrasonographic appearance of ovary helps to predict the number of viable embryos. In ET cycles, dexamethasone obviously improves the pregnancy rate. If the minimum P4 value before endometrial transformation cannot be kept below 0.45 ng/ml, we may consider cycle cancellation. Moreover, it is suggested that BMI of nonclassic 21-OHD women is regulated below 23.36 kg/m2.


Assuntos
Hiperplasia Suprarrenal Congênita/patologia , Fertilização In Vitro , Indução da Ovulação , Resultado da Gravidez , Adulto , Índice de Massa Corporal , Transferência Embrionária , Embrião de Mamíferos/metabolismo , Feminino , Humanos , Gravidez , Curva ROC
10.
Fertil Steril ; 112(2): 371-377, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31126712

RESUMO

OBJECTIVE: To investigate whether live birth rate (LBR) following frozen-thawed embryo transfer in letrozole-stimulated cycles (L-FET) differs from LBR after artificial-cycle frozen-thawed embryos transfers (AC-FET) in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENT(S): A total of 2,664 patients with PCOS who fulfilled the inclusion criteria were enrolled in the period from 2011 to 2016. INTERVENTIONS(S): Letrozole use versus hormone replacement therapies during FET. MAIN OUTCOME MEASURE(S): LBR per embryo transfer was the primary outcome. The secondary end points included ongoing and clinical pregnancy rate, cancellation rate, endometrial thickness, and pregnancy loss rate. Multivariable logistic regression analysis was performed to adjust for potential confounders. RESULT(S): In our crude analysis, LBR per embryo transfer was similar between groups (54.4% in the L-FET vs. 50.7% for the AC-FET). The crude odds of pregnancy loss was significantly lower in L-FET compared with AC-FET (9.1% vs. 17%). Nonetheless, after adjusting for possible confounding factors, LBR was significantly higher in L-FET compared with AC-FET. Moreover, the rates of pregnancy loss remained consistently lower in the L-FET group than in the AC-FET group. CONCLUSION(S): In patients with PCOS undergoing FET, letrozole use for endometrial preparation was associated with higher LBR compared with artificial cycles, albeit after statistical adjustment for confounding factors. Future prospective randomized studies are needed to verify our findings.

12.
Reprod Biomed Online ; 38(6): 892-900, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30954432

RESUMO

RESEARCH QUESTION: What are the live birth rates and neonatal outcomes following cleavage-stage embryo transfer and blastocyst transfer in a freeze-all treatment scenario? DESIGN: This was a retrospective cohort study. All good-quality embryos were frozen on the third day; the remaining embryos were grown on until they reached blastocyst stage and then frozen. Between 2007 and 2016, 11,801 patients underwent cleavage-stage embryo transfer and 1009 patients underwent blastocyst transfer in the first treatment cycle using the freeze-all strategy. The live birth rate and neonatal outcomes were evaluated. RESULTS: The live birth rate in the first frozen embryo transfer cycle was higher following blastocyst transfer than following cleavage-stage transfer (69.1% versus 55.5%, P < 0.01), but there was no difference in live birth rate in the second frozen embryo transfer cycle between blastocyst transfer and cleavage-stage transfer (45.2% versus 52.7%, P > 0.05). Similarly, no difference was found in the cumulative live birth rate for the first complete IVF cycle (71.1% versus 69.2%, P > 0.05). Blastocyst transfer gave a higher risk of preterm singleton delivery than did cleavage-stage transfer. However, there was no difference in the risk of early preterm delivery, low birth weight, very low birth weight, high birth weight and very high birth weight between the two groups. CONCLUSIONS: There is no evidence to support the superiority of blastocyst transfer compared with cleavage-stage transfer in a freeze-all treatment scenario. There may be a higher risk of preterm singleton delivery following blastocyst transfer than following cleavage-stage transfer but further studies are needed to verify this.

13.
J Med Genet ; 56(7): 471-480, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30877238

RESUMO

BACKGROUND: Successful human reproduction requires normal spermatogenesis, oogenesis, fertilisation and early embryonic development, and abnormalities in any of these processes will result in infertility. Early embryonic arrest is commonly observed in infertile patients with recurrent failure of assisted reproductive technology (ART). However, the genetic basis for early embryonic arrest is largely unknown. OBJECTIVE: We aim to identify genetic causes of infertile patients characterised by early embryonic arrest. METHODS: We pursued exome sequencing in a proband with embryonic arrest from the consanguineous family. We further screened candidate genes in a cohort of 496 individuals diagnosed with early embryonic arrest by Sanger sequencing. Effects of mutations were investigated in HeLa cells, oocytes and embryos. RESULTS: We identified five independent individuals carrying biallelic mutations in NLRP2. We also found three individuals from two families carrying biallelic mutations in NLRP5. These mutations in NLRP2 and NLRP5 caused decreased protein expression in vitro and in oocytes and embryos. CONCLUSIONS: NLRP2 and NLRP5 are novel mutant genes responsible for human early embryonic arrest. This finding provides additional potential diagnostic markers for patients with recurrent failure of ART and helps us to better understand the genetic basis of female infertility characterised by early embryonic arrest.

14.
Sci Transl Med ; 11(485)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30918116

RESUMO

Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms three species, GLY0, GLY1, and GLY2. Here, we describe four independent families in which mutations in PANX1 cause familial or sporadic female infertility via a phenotype that we term "oocyte death." The mutations, which are associated with oocyte death, alter the PANX1 glycosylation pattern, influence the subcellular localization of PANX1 in cultured cells, and result in aberrant PANX1 channel activity, ATP release in oocytes, and mutant PANX1 GLY1. Overexpression of a patient-derived mutation in mice causes infertility, recapitulating the human oocyte death phenotype. Our findings demonstrate the critical role of PANX1 in human oocyte development, provide a genetic explanation for a subtype of infertility, and suggest a potential target for therapeutic intervention for this disease.

15.
Hum Genet ; 138(4): 327-337, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30810869

RESUMO

The human zona pellucida (ZP) is an extracellular glycoprotein matrix composed of ZP1, ZP2, ZP3, and ZP4 surrounding the oocyte, and it plays an important role in sperm-egg interactions during fertilization. Structural and functional changes in the ZP can influence the process of fertilization and lead to female infertility. Previous studies have identified mutations in ZP1, ZP2, and ZP3 that lead to female infertility caused by oocyte degeneration, empty follicle syndrome, or in vitro fertilization failure. Here we describe seven patients from six independent families who had several abnormal oocytes or suffered from empty follicle syndrome, similar to the previously reported phenotypes. By whole-exome sequencing and Sanger sequencing, we identified several novel mutations in these patients. These included three homozygous mutations in ZP1 (c.1708G > A, p.Val570Met; c.1228C > T, p.Arg410Trp; c.507del, p.His170Ilefs*52), two mutations in a compound heterozygous state in ZP1 (c.1430 + 1G > T, p.Cys478X and c.1775-8T > C, p.Asp592Glyfs*29), a homozygous mutation in ZP2 (c.1115G > C, p.Cys372Ser), and a heterozygous mutation in ZP3 (c.763C > G, p.Arg255Gly). In addition, studies in CHO cells showed that the mutations in ZP1, ZP2, and ZP3 might affect the corresponding protein expression, secretion, and interaction, thus providing a mechanistic explanation for the phenotypes. Our study expands the spectrum of ZP gene mutations and phenotypes, and provides a further understanding of the pathogenic mechanism of ZP gene mutations in vitro.


Assuntos
Infertilidade Feminina/genética , Mutação , Glicoproteínas da Zona Pelúcida/genética , Zona Pelúcida/patologia , Adulto , Animais , Células CHO , Consanguinidade , Cricetinae , Cricetulus , Análise Mutacional de DNA , Feminino , Humanos , Infertilidade Feminina/patologia , Masculino , Folículo Ovariano/anormalidades , Folículo Ovariano/patologia , Linhagem , Síndrome , Zona Pelúcida/metabolismo
16.
J Hum Genet ; 64(5): 379-385, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30765866

RESUMO

Oocyte maturation arrest results in primary female infertility, but the genetic etiology of this phenotype remains largely unknown. Previously, we and other groups have reported that biallelic mutations in PATL2 are mainly responsible for human oocyte germinal vesicle-stage arrest and that the specific phenotype varies for different mutations. Here, we identified four novel missense mutations (p.V260M, p.Q300*, p.T425P, and p.D293Y), a novel frameshift mutation (p.N239Tfs*9), and a reported splicing mutation (p.R75Vfs*21) in PATL2 in seven affected individuals from five unrelated families, showing a multiplicity of phenotypes in oocyte maturation arrest, fertilization failure, or embryonic developmental arrest, which further expands the mutational and phenotypic spectrum in patients with PALTL2 mutations. This work further indicates the critical role of PATL2 in oocyte maturation and early embryo development and will provide a basis for pursuing the determination of genetic variation in PALT2 as an additional criterion for evaluating the quality of oocytes and embryos for assisted reproduction techniques.


Assuntos
Infertilidade Feminina/genética , Mutação de Sentido Incorreto , Proteínas Nucleares/genética , Proteínas de Ligação a RNA/genética , Substituição de Aminoácidos , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/patologia , Desenvolvimento Embrionário/genética , Feminino , Humanos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Proteínas Nucleares/metabolismo , Oócitos/metabolismo , Oócitos/patologia , Proteínas de Ligação a RNA/metabolismo
17.
Medicine (Baltimore) ; 98(7): e14075, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762725

RESUMO

OBJECTIVE: To study if hysteroscopy (HSC) before starting an in-vitro fertilization (IVF) cycle improves IVF outcomes in women with recurrent implantation failure (RIF). METHODS: The Medline, Cochrane, EMBASE, and Google Scholar databases were searched using the following keywords until March 31, 2017: in-vitro fertilization; infertility; hysteroscopy; recurrence; embryo implantation; and pregnancy. Randomized controlled trials (RCTs), two-arm prospective studies, and retrospective studies were included. RESULTS: Three RCTs, 3 nonrandomized prospective studies, and 2 retrospective cohort studies were included. The eligible studies included 3932 women with RIF: 1841 in the HSC group and 2091 in the control group. The clinical pregnancy rate and implantation rate was significantly higher in the HSC group compared with the control group (for clinical pregnancy rate, pooled odds ratio [OR] = 1.64, 95% confidence intervals [CI]: 1.30-2.07, P < 0.001; for implantation rate, pooled OR = 1.22, 95% CI: 1.02-1.45, P = 0.025). The live birth rate (pooled OR = 1.30, 95% CI: 0.90-1.88, P = 0.168) and the miscarriage rate (pooled OR = 0.94, 95% CI: 0.66-1.35, P = 0.744) of the 2 groups were not statistically significantly. CONCLUSIONS: HSC improved the implantation rate and clinical pregnancy rates, but failed to improve live birth rate and did not affect the miscarriage rate in women with RIF undergoing IVF. Since HSC plays a significant role in pregnancy and birth outcomes of women with RIF, further studies are warranted.


Assuntos
Implantação do Embrião , Fertilização In Vitro/métodos , Fertilização In Vitro/estatística & dados numéricos , Histeroscopia/estatística & dados numéricos , Aborto Espontâneo/epidemiologia , Feminino , Humanos , Nascimento Vivo/epidemiologia , Razão de Chances
18.
Clin Genet ; 95(4): 520-524, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30628060

RESUMO

Successful fertilization is fundamental for sexual reproduction. After undergoing a series of molecular and morphological changes, the haploid sperm fuses with the haploid oocyte to create a diploid zygote. Defects in this process might lead to human fertilization failure. We have previously found homozygous mutations in WEE2 that are responsible for human fertilization failure, but the genetic basis of human fertilization failure requires further investigation. In the present study, we screened for WEE2 mutations in a new cohort of patients with fertilization failure. Through Sanger sequencing of WEE2 exons, we identified seven novel mutations and two reported mutations in WEE2 from six affected individuals. Morphologically normal PB1 oocytes can be retrieved from all patients. However, most of the oocytes cannot be fertilized successfully. These findings confirmed our previous research and expanded the mutational spectrum of WEE2, making it a potential genetic diagnostic marker for those suffering from human fertilization failure.

19.
Syst Biol Reprod Med ; 65(1): 54-60, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30526119

RESUMO

This large retrospective study was conducted to compare the risk for birth defects among infants conceived by in vitro fertilization (IVF) with that among infants conceived by intracytoplasmic sperm injection (ICSI) and to explore the effect of frozen embryo transfer (FET) on the risk for birth defects among infants born by IVF and ICSI. All patients who received assisted reproductive technology (ART) treatment and who underwent childbirth during the period January 2005-August 2017 were included in this study. There were 18,221 births after ART included in the analysis; of these births, 12,649 were conceived by IVF, and 5,572 were conceived by ICSI. In the study, the prevalence of any birth defect in singleton infants was 1.15% with the use of IVF and 1.38% with the use of ICSI, and that in twin infants increased to 2.74% by IVF and 2.58% by ICSI. However, no significant difference between IVF and ICSI was found among all infants, singleton births or twin births. Additionally, in assessing ART infants born after FET, we did not detect a difference in the risk for birth defects between infants born by IVF and those born by ICSI. These results indicate that among the entire cohort of children conceived from ART and among the children conceived from FET, the risk for birth defects after ICSI is similar to that after IVF.Abbreviations: IVF: in vitro fertilization; ICSI: intracytoplasmic sperm injection; FET: frozen embryo transfer; ART: assisted reproductive technology; ET: embryo transfer; BMI: body mass index; OHSS: ovarian hyperstimulation syndrome; CMOH: Chinese Ministry of Health; ICD-10: International Classification of Diseases, 10th edition; PTB: preterm birth; OR: odds ratio; aOR: adjusted odds ratio; CI: confidence interval.


Assuntos
Anormalidades Congênitas/etiologia , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Risco , Injeções de Esperma Intracitoplásmicas/estatística & dados numéricos
20.
Fertil Steril ; 2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30458993

RESUMO

OBJECTIVE: To investigate the effect of embryo culture duration on birth weight in vitrified-warmed cycles. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENT(S): A total of 4,201 women who gave birth to 3,520, 215, and 466 live-born singletons after frozen-thawed cleavage-stage (day 3) and day 5 and day 6 blastocyst transfer, respectively. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Neonatal birth weight. RESULT(S): The mean birth weight did not differ between the three study groups. However, the gestational age- and sex-adjusted birth weight (Z-scores) of singletons and the proportion of large-for-gestational-age (LGA) babies were significantly higher after day 5 and day 6 transfer than after transfer of day 3 embryos. Furthermore, multiple linear regression analysis indicated that gestational age, parental body mass index, neonatal sex, and length of the culture period all had significant and strong impacts on birth weight of singleton newborns. CONCLUSION(S): In the vitrified-warmed transfer cycles, birth weight Z-scores and the proportion of LGA infants were both higher in singletons born after blastocyst transfer than after transfer of cleavage-stage embryos. This finding suggests that the effect of culture duration was not overcome by transfer of embryos into a more physiologic uterine environment.

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