Paradoxical fall in proteinuria during pregnancy in an LCAT-deficient patient—A case report

A 29-year-old lady was diagnosed with lecithin:cholesterol acyltransferase (LCAT) deficiency having presented with bilateral corneal clouding, severely reduced high density lipoproteins cholesterol, and proteinuria. She is a compound heterozygote with two LCAT gene mutations, one of which is novel, c.321C>A in exon 3. Surprisingly, the level of proteinuria significantly improved during pregnancy, despite stopping the angiotensin-converting enzyme inhibitor. However, LCAT concentration and activity remained identical during pregnancy and postpartum. Her pregnancy was complicated by rising triglyceride levels from the second trimester requiring treatment with omega-3 fatty acid and fenofibrate. In the last trimester, a further complication arose when she became hypertensive and proteinuria worsened. She was diagnosed with pre-eclampsia and had an emergency cesarean section at 39 weeks delivering a healthy baby. This case adds to the knowledge of the pathophysiology of LCAT deficiency during pregnancy and will be useful in future patient management.     

Does high estrogen level negatively affect pregnancy success in frozen embryo transfer?

IntroductionHigh estrogen levels could reduce pregnancy rates by disrupting the implantation of the embryo into the endometrium in patients treated with fresh cycles of in vitro fertilization. The aim of the present study was to investigate the effect of estrogen levels on the pregnancy and abortion rate in autologous frozen embryo transfer with hormone replacement therapy (HRT).Material and methodsA historical cohort study was conducted in an academic setting to investigate the effect of estrogen levels on the pregnancy and abortion rates for all autologous artificial frozen embryo transfer cycles performed from January 2016 to January 2018. Serum estradiol levels recorded on day 2 or 3 of the cycle were stated as e1, and levels recorded on the day of progesterone were indicated as e2. Human chorionic gonadotropin (β-hCG) positivity, which was examined 14 days after the transfer, was used to evaluate biochemical pregnancy. Abortion was defined as the termination of pregnancy before the 20^th gestational week.ResultsThere were 130 patients with unexplained infertility, 20 patients with poor ovarian reserve, and 54 patients with male factor. Of the patients with unexplained infertility, poor ovarian reserve, and male factor, 58, 4, and 27 of them were pregnant, respectively. No statistically significant difference was found between the e1 and e2 levels of the pregnant and non-pregnant groups (p = 0.273, p = 0.219). In addition, there was no statistically significant difference between e2 levels in terms of the abortion rate (p = 0.722).ConclusionsIn autologous frozen embryo transfer with HRT, estrogen levels did not have a significant effect on the pregnancy or abortion rate. Therefore, estrogen levels do not need to be monitored in frozen embryo transfer with HRT.     

SHORT COMMUNICATION: CD3− CD56+ CD16+ Natural Killer Cells and Improvement of Pregnancy Outcome in IVF/ICSI Failure After Additional IVIG‐Treatment

Citation Heilmann L, Schorsch M, Hahn T. CD3^? CD56⁺ CD16⁺ Natural killer cells and improvement of pregnancy outcome in IVF/ICSI failure after additional IVIG‐treatment. Am J Reprod Immunol 2010; 63: 263–265 Problem The purpose of this retrospective, observational study was to investigate whether additional treatment with intravenous immunglobulin (IVIG) increased the rate of successful pregnancies after repeated implantation failure (RIF). The retrospective data were compared with data of patients without IVIG‐therapy from the meta‐analysis of Clark et al. Method of study A total of 188 women with 226 treatment cycles between 2007 and 2009 were evaluated for IVIG therapy. The percentage of NK cells was measured two times before a new embryo transfer (only women with NK cell percentages >12% were included) and after embryo transfer at a positive pregnancy test. Results In comparison with the meta‐analysis of Clark et al., we observed a pregnancy rate of 50.5%, an implantation rate of 21% and a miscarriage rate of 16.8%. In 42%/IVIG‐ patient or 34.9%/embryo transfer, we observed a live born baby. The live born rate per embryo was 16.6%. In accordance with the study of Kwak et al., we indicate a decrease in the NK cells in patients with improved pregnancy outcome. Conclusion In a subgroup of RIF‐patients with high level of CD56⁺ CD16⁺ NK‐cells the additional application of IVIG leads to a favourable pregnancy outcome.     

PI3KCA mutation status is of limited prognostic relevance in ER-positive breast cancer patients treated with hormone therapy

PI3K/AKT/mTOR pathway alterations are frequent in patients with infiltrating breast cancer (IBC). Their clinical and pathological relevance has been insufficiently documented. We evaluated PI3KCA for mutations and the expression of PTEN, AKT, mTOR and p70S6K by immunohistochemistry in 246 IBC patients treated with hormone therapy (median follow-up, 97 months). A PI3KCA mutation was observed in 50 out of 229 informative cases (21.8 %), PTEN loss in 107 out of 210 (51 %), moderate/high level of expression of AKT in 133 out of 188 (71 %), moderate/high level of expression of mTOR in 173 out of 218 (79 %) and moderate/high level of expression of p70S6K in 111 out of 192 cases (58 %). PI3KCA mutation was associated with the absence of Her2/neu amplification/overexpression and a low level of MIB1/Ki-67 labelling. The expression of p70S6K was associated with a high level of mTOR immunoreactivity, and high PTEN expression was associated with high AKT expression level. Univariate analysis showed that PI3KCA mutation status was not associated with clinical outcome in the series as a whole or in the node-negative subgroup. However, in the node-positive subgroup, exon 9 PI3KCA mutation was associated with unfavourable overall survival (OS), although its impact on the final model in multivariate analysis seemed to be limited. Of the other markers, only high p70S6K expression was associated with a significantly prolonged OS. PI3KCA mutation status is of limited prognostic relevance in oestrogen receptor-positive breast cancer patients treated with hormone therapy.     

A Novel C-terminal Nonsense Mutation,Q315X,of the Aryl Hydrocarbon Receptor-Interacting Protein Gene in a Japanese Familial Isolated Pituitary Adenoma Family

Although the cause of familial isolated pituitary adenoma (FIPA) remains unknown in many cases, germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene were identified in approximately 20 % of families with FIPA. We investigated the AIP gene mutation by a standard sequencing method in 12 members of a Japanese two-generation FIPA family, which includes 3 patients with early-onset acromegaly. Multiplex ligation-dependent probe amplification analysis in a tumor sample was attempted to examine the loss of heterozygosity (LOH) in the locus. The effect of the detected mutation on cell proliferation was investigated. A germline mutation of c.943C?>?T (p.Q315X) generating an AIP protein with the C-terminal end deleted was found in the FIPA family. Biallelic inactivation of AIP by a combination of the germline mutation and LOH at 11q13 was confirmed in the tumor. The nonsense mutation disrupted the ability to inhibit cell proliferation. We conclude that p.Q315X mutation in the AIP gene is a pathogenic variant and the C-terminal region of AIP plays an important role in the predisposition to pituitary adenomas.     

Cancer and male infertility: Gamete intra-Fallopian transfer or in-vitro fertilization after failed ovarian stimulation and intrauterine insemination in unexplained infertility?

A prospective randomized study was designed to compare gameteintra-Fallopian transfer (GIFT) and in-vitro fertilization (IVF)and embryo transfer in the treatment of couples who have failedto conceive after at least three cycles of ovarian stimulationand intrauterine insemination (IUI). A total of 69 couples withprimary unexplained infertility of at least 2 years' durationplus at least three failed cycles of ovarian stimulation andIUI were randomly allocated to either GIFT or IVF/embryo transfer.The clinical pregnancy rate was 34% after GIFT treatment and50% after IVF/embryo transfer. This difference was not statisticallysignificant. The twin rate in the IVF/embryo transfer groupwas higher than in the GIFT group (53 versus 17%, P = 0.005).We conclude that patients with unexplained infertility and failedovarian stimulation and IUI can still achieve encouraging pregnancyrates with IVF/embryo transfer or GIFT. Since IVF/embryo transferis the least invasive of the two procedures and may yield diagnosticinformation, we would favour this therapy; however, the numberof embryos transferred should be reduced to two to reduce therisk of twin pregnancy.     

Normal plasma apoB48 despite the virtual absence of apoB100 in a compound heterozygote with novel mutations in the MTTP gene

“Normotriglyceridemic abetalipoproteinemia (ABL)” was originally described as a clinical entity distinct from either ABL or hypobetalipoproteinemia. Subsequent studies identified mutations in APOB gene which encoded truncated apoB longer than apoB48. Therefore, “Normotriglyceridemic ABL” can be a subtype of homozygous familial hypobetalipoproteinemia. Here, we report an atypical female case of ABL who was initially diagnosed with “normotriglyceridemic ABL”, because she had normal plasma apoB48 despite the virtual absence of apoB100 and low plasma TG level. Next generation sequencing revealed that she was a compound heterozygote of two novel MTTP mutations: nonsense (p.Q272X) and missense (p.G709R). We speculate that p.G709R might confer residual triglyceride transfer activity of MTTP preferentially in the intestinal epithelium to the hepatocytes, allowing production of apoB48. Together, “normotriglyceridemic ABL” may be a heterogenous disorder which is caused by specific mutations in either APOB or MTTP gene.     

Autoantibody induction and adipokine levels in patients with psoriasis treated with infliximab

This study was aimed to analyse the prevalence of antinuclear antibodies in patients with psoriasis after treatment with infliximab and correlates the development of antibodies with both response to treatment and adipokines levels. Serum levels of ANA, anti-dsDNA, anti-histone, anti-nucleosome and anti-ENA antibodies at baseline after 2 and 12 months of treatment with infliximab were measured in 27 patients with psoriasis, as well as in 27 matched controls. Serum C-reactive protein (CRP), chemerin, visfatin and resistin were also assessed. The prevalence of ANA increased from 22 to 37 % and 63 % (p < 0.01) during treatment with infliximab, with a gradual progressive increase both in ANA titre and in percentage of ANA pattern. The prevalence of other antibodies also increased from 7 to 30 % and 48 % (p < 0.01) for anti-ds-DNA and from 7 to 26 % and 37 % for anti-nucleosome antibodies (p < 0.05), whereas the prevalence of anti-histone and anti-ENA antibodies was unchanged throughout the study period. Basal chemerin, resistin and CRP levels were higher in patients than in controls, and their levels progressively normalized during treatment (p < 0.01). Conversely, visfatin levels gradually increased (p < 0.01). ANA+ patients tended to show a faster decrease in PASI score, CRP and chemerin levels after 2 months, but the PASI score did not differ between ANA+ and ANA? patients at 12 months. A higher increase of visfatin was also found in ANA+ patients at 2 and 12 months. The antinuclear antibody response induced by infliximab was restricted to ANA, anti-dsDNA and anti-nucleosome antibodies. Patients who developed ANA positivity showed a faster clinical, inflammatory and immunological response to infliximab therapy.     

A retrospective biochemical,molecular, and neurocognitive review of Saudi patients with argininosuccinic aciduria

A retrospective review was compiled of 54 patients with argininosuccinic aciduria who were either identified through the Saudi National Newborn Screening Program or diagnosed clinically from January 2000 to December 2015. The duration of follow-up is from 2 to 19 years. The majority of patients (65%) originated from the central province of Saudi Arabia. The mean patient age at review was 10 years (2–19 years), 92% received an early diagnosis (<28 days of age) and most were symptomatic at the time of the diagnosis (n?=?34). Normal ammonia at diagnosis was reported in 30% of patients, who were detected under the newborn metabolic screen (n?=?5/16). A very high rate of consanguinity was observed in our cohort (98%). Developmental delay was the most detectable long term neurocognitive consequence followed by seizure disorder; 90.7% (n?=?49) and 62.9% (n = 34) respectively. As expected, the severe neonatal form was the major presentation. The most common variant identified in this cohort was the previously reported founder c.1060C > T; p.(Gln354*) nonsense mutation in the ASL gene. In addition, the frequency of hyperammonemia was higher in patients homozygous for c.1060C > T; p.(Gln354*) compared to the other mutations. Interestingly, frequent thrombocytosis with the mean level of 717 × 10⁹/L (range?=?457–1169?×?10⁹/L) was observed in 96% of the patients with no clear explanation.     

未成熟卵体外成熟与体外受精妊娠胚胎移植14 d血清人绒毛膜促性腺激素 β亚单位水平的比较*

背景：相关研究表明,体外受精与胚胎移植治疗妊娠后血清人绒毛膜促性腺激素β亚单位水平对妊娠结局有预测作用,未成熟卵体外成熟治疗妊娠后血清人绒毛膜促性腺激素β亚单位水平对妊娠结局的预测作用不详。 目的：比较不孕症患者体外受精与胚胎移植和未成熟卵体外成熟治疗妊娠后血清人绒毛膜促性腺激素β亚单位水平,探讨血清人绒毛膜促性腺激素β亚单位水平对未成熟卵体外成熟治疗妊娠患者的预测价值。 方法：采用回顾性分析的方法,以在本中心行未成熟卵体外成熟治疗后妊娠实验阳性的42例患者为研究组,同期行体外受精治疗后妊娠实验阳性的66例患者作为对照组,比较两组患者胚胎移植后第14天血清人绒毛膜促性腺激素β亚单位水平。 结果与结论：胚胎移植后14 d,分别在研究组和对照组内,单、双胎妊娠患者血清人绒毛膜促性腺激素β亚单位水平差异均有显著性意义。血清人绒毛膜促性腺激素β亚单位水平≥ 800 U/L时,两组双胎妊娠的发生率均明显增高。提示血清人绒毛膜促性腺激素β亚单位水平对未成熟卵体外成熟治疗后妊娠患者的结局具有预测价值,未成熟卵体外成熟/体外受精妊娠胚胎移植14 d血清人绒毛膜促性腺激素β亚单位水平及其对妊娠结局的预测是相同的。     

高通量测序确诊一例ASXL3基因变异所致的Bainbridge-Ropers综合征

目的对1例表现为精神发育迟滞、语言运动发育迟缓的患儿进行临床及遗传学分析。方法对患儿进行常规染色体G显带核型以及高通量测序分析,对疑似致病变异进行Sanger测序验证和生物信息学分析。结果患儿ASXL3基因存在c.4090G>T(p.Gly1364X)杂合变异,其父母均未携带相同变异,为新生变异。结论ASXL3基因c.4090G>T(p.Gly1364X)变异可能是患儿的遗传学病因。     

Report of two unrelated families with Jalili syndrome and a novel nonsense heterozygous mutation in CNNM4 gene

Jalili syndrome (JS) is an autosomal recessive disease characterized by a combination of cone-rode retinal dytrophy (CRD) and amelogenesis imperfect (AI). Mutations in cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) gene cause JS. Here we described 2 families (3 members) affected by JS. In the first family, JS was caused by the homozygous p.Leu324Pro (c.971T > C) missense mutation and the affected patient developed both CRD and AI. In the second family, a specific combination of a compound heterozygous mutation was found – the p.Leu324Pro (c.971T > C) missense transition and the novel p.Tyr581* (c.1743C > G) nonsense mutation. The proband showed CRD and AI, but her father just developed eye alterations. Together, these findings suggest that the p.Leu324Pro mutation in homozygosis induces a complete phenotype with both CRD and AI, but in heterozygosis and in composition with the novel p.Tyr581* nonsense mutation in CNNM4 promotes variable clinical expressivity, particularly with lack of dental phenotypes. These different phenotypes could be explained by deletions affecting the proband's homologous allele, epistasia or interactions with environmental factors leading to residual activity of protein.     

A case of severe autosomal recessive spinocerebellar ataxia type 18 with a novel nonsense variant in GRID2

Autosomal-recessive spinocerebellar ataxia type 18 (SCAR18) is a rare neurologic disorder. It is caused by bi-allelic aberrations in the GRID2 gene, encoding an ionotropic glutamate receptor. In total, 20 affected individuals with mainly homozygous/compound heterozygous intragenic deletions/duplications, two different missense variants and one nonsense variant in GRID2 have been reported, so far. SCAR18 is characterized by delayed psychomotor development, intellectual disability, severely impaired gait due to cerebellar ataxia, ocular movement abnormalities, and cerebellar atrophy in brain imaging.By trio exome sequencing, we now identified a novel homozygous nonsense variant (c.568C > T; p.Gln190*) in GRID2 in a four year old female from a consanguineous family who presented with a particularly severe manifestation of SCAR18. The girl was born after an uneventful pregnancy and showed early-onset, profoundly delayed psychomotor development with no achieved psychomotor milestones at age 4 years. Additionally, she presented with severe muscular hypotonia, progressive truncal and appendicular ataxia, binocular vertical nystagmus, central hearing loss and incomplete loss of sight. She was dystrophic, interacted only very little and had behavioral anomalies such as eating hair and bruxism. Brain imaging showed cerebellar hypoplasia, extended cerebrospinal fluid spaces and beginning reduction of cerebral volume.Our findings further delineate the mutational and clinical spectrum of GRID2-associated spinocerebellar ataxia type 18 and indicate that homozygous nonsense variants are possibly associated with the severe end of the SCAR18 phenotypic spectrum.     

A classification system for split-hand/ foot malformation (SHFM): A proposal based on 3 pedigrees with WNT10B mutations

SHFM6 (OMIM 225300) is caused by WNT10B pathogenic variants (12q13.12). It is one of the rarest forms of SHFM; with only seven pathogenic variants described in the world literature. Furthermore, it has not been determined if SHFM6 has specific phenotypic characteristics.In this paper, we present a case series of three unrelated families with SHFM6 caused by three novel WNT10B pathogenic variants. The index patient of the first family was homozygous for the nonsense variant c.676C > T (p.Arg226*) in the WNT10B gene. The index case of the second family had a homozygous splice variant c.338-1G > C in the WNT10B gene. Finally, the index case of the third family carried two different variants in the WNT10B gene: A nonsense variant (p.Arg226*), and a missense variant (p.Gln86Pro). The latter represents the first compound heterozygous pathogenic variant related to SHFM6. We also offer a classification system for the hand/foot defects to illustrate the specific phenotypic characteristics of SHFM6. Based on this classification and a review of all previously reported cases, we demonstrate that SHFM6 caused by WNT10B pathogenic variants have the following characteristics: more severe feet defects (compared to the hand defects), polydactyly, severe flexion digital contractures, and phalangeal dysplasia.     

Low BRAF and NRAS expression levels are associated with clinical benefit from DTIC therapy and prognosis in metastatic melanoma

Metastatic melanoma is characterized by a poor response to chemotherapy. Furthermore, there is a lack of established predictive and prognostic markers. In this single institution study, we correlated mutation status and expression levels of BRAF and NRAS to dacarbazine (DTIC) treatment response as well as progression-free and overall survival in a cohort of 85 patients diagnosed with advanced melanoma. Neither BRAF nor NRAS mutation status correlated to treatment response. However, patients with tumors harboring NRAS mutations had a shorter overall survival (p < 0.001) compared to patients with tumors wild-type for NRAS. Patients having a clinical benefit (objective response or stable disease at 3 months) on DTIC therapy had lower BRAF and NRAS expression levels compared to patients progressing on therapy (p = 0.037 and 0.003, respectively). For BRAF expression, this association was stronger among patients with tumors wild-type for BRAF (p = 0.005). Further, low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population (p = 0.004 and <0.001, respectively). Contrasting low NRAS expression levels, which were associated with improved overall survival in the total population (p = 0.01), low BRAF levels were associated with improved overall survival only among patients with tumors wild-type for BRAF (p = 0.013). These findings indicate that BRAF and NRAS expression levels may influence responses to DTIC as well as prognosis in patients with advanced melanoma.     

The window for embryo transfer in oocyte donation cycles depends on the duration of progesterone therapy

In 192 oocyte donation cycles performed between January 1993 and July 1996, we examined the width of 'the window for embryo transfer' using standard hormonal replacement methods. All transfers were performed within 48 h of insemination. We varied the day of embryo transfer with regard to the initiation of progesterone therapy and, thus, the duration of endometrial exposure to progesterone and analysed the resulting pregnancy rates. Patients were divided into five groups (I-V) and embryo transfers were performed 2, 3, 4, 5 or 6 days following initiation of progesterone therapy. The number of pregnancies per transfer cycle achieved in groups I-V were 0 (0%), 3 (12%), 16 (40%), 29 (48.3%), and 10 (20.4%) respectively. The increased pregnancy rate in group III in comparison to group II is statistically significant (P < 0.03). Furthermore, the pregnancy rate in group IV (5 days of progesterone administration before embryo transfer) was significantly higher than in group V (6 days of progesterone administration before embryo transfer; P < 0.005). We also noted that, when embryos were transferred 4 or 5 days after initiation of progesterone therapy, the pregnancy rates were not significantly different between menopausal and cycling recipients (50% vs 43.7%). Our results indicate that the window for embryo transfer is dependent on duration of treatment with progesterone; it begins approximately 48 h after starting progesterone administration and lasts for approximately 4 days. The optimum period for transferring embryos at the 4- to 8-cell stage corresponds to cycle days 18 and 19. Transfers performed on the 17th and 20th days of the cycle can result in successful implantation, although the rates of implantation are highest when transfers are done on days 18 and 19.      

Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment

The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p < 0.001). In patients with a Karnofsky Performance Status ≥70 and those <70, survival was respectively 16 and 5.5 months (p < 0.001). The median survival from brain metastasis in patients with solitary brain metastasis, with and without systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.     

一个淋巴水肿-双行睫综合征家系的FOXC2基因变异分析

目的对1个淋巴水肿-双行睫综合征(lymphedema-distichiasis syndrome,LDS)家系患者的FOXC2基因进行变异分析,明确患者的致病原因。方法采集家系成员血液样本并提取DNA和蛋白,对先证者进行全外显子组测序及生物信息学分析,确定可疑致病变异后应用Sanger测序进行家系验证、Western印迹技术检测蛋白表达量的变化。结果测序结果显示先证者和患病母亲均携带FOXC2基因c.177C>G(p.Tyr59X)杂合无义变异,该变异目前尚未被报道过,Western印迹检测显示FOXC2蛋白表达下降。其母在早孕期B超提示胎儿NT增厚,孕21+1周行羊水穿刺对胎儿进行产前诊断,产前基因诊断结果提示胎儿也携带c.177C>G变异。结论FOXC2基因c.177C>G无义变异是患儿的致病原因,并导致Foxc2蛋白表达下降,胎儿NT增厚可能和Foxc2表达量下降有关。本研究结果扩大了FOXC2基因变异谱。     

Molecular diagnosis of bacterial vaginosis: impact on IVF outcome

Bacterial vaginosis can increase obstetrical complications such as miscarriage, premature rupture of membranes and preterm delivery. The aim of our study was first to assess BV prevalence for infertile patients treated by in vitro fertilisation (IVF) using both the Nugent score and polymerase chain reaction (PCR), and then to assess the impact of BV on the pregnancy rate after IVF. Vaginal samples were obtained from women followed for IVF in our Assisted Reproduction Technology (ART) Unit between August 2010 and April 2011. For each patient, two techniques were performed to diagnose BV: Gram staining to assess the Nugent score and a quantitative molecular analysis using a specific real-time PCR assay. Two groups were studied: normal flora (BV?) and BV (BV+). The primary outcome measure was the implantation rate. The secondary outcomes were clinical pregnancy rate, early and late miscarriage, premature rupture of membranes, preterm delivery, mode of delivery and birthweight. A total of 307 patients were included. PCR revealed a prevalence of BV of 9.45 %. Among women who performed vaginal douching, 22.2 % were BV+, whereas 7.9 % of patients who did not douche were BV+ (p?=?0.028). The embryo implantation rate was decreased between the BV? and BV+ groups (36.3 % vs. 27.6 %, p?=?0.418), but it was not significant. Obstetrical outcomes did not present significant statistical differences among the groups. Vaginal douching significantly enhanced BV in women treated with IVF. We also observed a non-significant decrease of embryo implantation rate and clinical pregnancy rate for women treated by IVF.