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PAPERS: S G Ralph, A J Rutherford, and J D Wilson Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study BMJ 1999; 319: 220-223 [Abstract] [Full text]

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Early pregancy loss, Bacterial vaginosis and lessons from medical histroy.

Rudiger Pittrof   (23 July 1999)

Microecology and therapy for bacterial vaginosis

Giuseppe Famularo   (9 August 1999)

The presence of bacterial vaginosis does not affect embryo implantation

Stephen Keay   (16 August 1999)

Early pregancy loss, Bacterial vaginosis and lessons from medical histroy. 23 July 1999
Rudiger Pittrof, Lecturer Maternal & Child Epidemiology Unit, London School of Hygiene and Tropical Med., London WC1E 7HT Send response to journal: Re: Early pregancy loss, Bacterial vaginosis and lessons from medical histroy.	Sir In their excellent paper Ralph, Rutherford and Wilson report an increased risk of early pregnancy loss in women with Bacterial vaginosis (BV) undergoing IVF treatment. This important finding may lead to reduced costs per maternity. The authors rightly demand intervention studies before a policy of BV screening and treatment in women undergoing IVF can be recommened. They do NOT suggest that screening and treatment or even presumptive treatment for BV should be offered to all women who are contemplating pregnancy or present in early pregnancy. I fully support this view. Even if interventions studies confirm the finding presented by Ralph, Rutherford and Wilson, generalisation to all women will be incorrect: Spontaneously conceived pregnancies are very different from those conceived during IVF. Normal pregnancies are not conceived following exposure to GhRh analogous, ovarian hyper stimulation, ovulation induction, oocyte collection and transfer of multiple embryos. Furthermore women undergoing IVF have different socio-demographic characteristics from those conceiving spontaneously. All this could contribute to the association between BV and abortion in women undergoing IVF. Not repeating the diethylstilbestrol (DES) experience with another drug must be the first lesson history has to teach us about interventions to prevent early pregnancy losses. This has to apply to all inteventions even to those using cheap and presumably safe drugs such Metronidazole.
Microecology and therapy for bacterial vaginosis 9 August 1999
Giuseppe Famularo, physician San camillo Hospital, Rome, Italy Send response to journal: Re: Microecology and therapy for bacterial vaginosis	Editor - Several strategies have been proposed for the treatment of bacterial vaginosis, a potentially serious disorder as shown by Ralph and colleagues (1). Most studies advocate to suppress the abnormal growth of those bacteria that inappropriately colonise the vaginal microenvironment with the use of antibiotics or probiotics (i.e. preparations of live bacteria), but the clinical impact and benefit are modest (2,3). The suppression of "wrong" colonising bacteria is not sufficient by itself to re-establish the ecological normality of vaginal microflora and bacteria used as probiotics could not have the entire spectrum of characteristics requested for a "ecologically correct" microbial balance. The production of lactic acid is crucial but additional properties should be considered. Only a limited number of strains of lactic acid-producing bacteria, reasonably those with a greater immuno-enhancing and a lower pro- inflammatory potential, is probably essential for the normal vaginal ecology. We have selected a Lactobacillus strain (L. brevis CD2) carrying the gene for arginine deaminase with the resulting ability to greatly lower the environmental concentrations of the pro-inflammatory mediator nitric oxide. Our preliminary results of probiotic treatment of bacterial vaginosis with L. brevis CD2 are encouraging. Under an ecological perspective, we suggest that not all lactic acid-producing probiotic bacteria should be indiscriminately regarded as normal biota. 1. Ralph SG, Rutherford AJ, Wilson JD. Influence of bacterial vaginosis on conception and miscarriage in the first trimester: a cohort study. BMJ 1999; 319: 220-223. 2. Joesoef MR, Schmid GP, Hillier SL. Bacterial vaginosis: review of treatment options and potential clinical implications for therapy: Clin Infect Dis 1999; 28 (Suppl. 1): S56-S65. 3. Chimura T. Ecological treatment of bacteriual vaginosis and vaginitis with Bio-three. Jpn J Antibiot 1998; 51: 759-763. Giuseppe Famularo and Claudio De Simone* Department of Emergency Medicine, San Camillo Hospital, Rome; * Department of Experimental Medicine, University of L'Aquila, Italy.
The presence of bacterial vaginosis does not affect embryo implantation 16 August 1999
Stephen Keay Send response to journal: Re: The presence of bacterial vaginosis does not affect embryo implantation	Editor, We read with interest Ralph et al's paper1 addressing the possible relationship between bacterial vaginosis and miscarriage in a large series of patients undergoing IVF. However it is important to recognise the limitations of this study. The increase in first trimester miscarriage rate in the bacterial vaginosis group is only statistically significant because of the higher proportion of "pre-clinical" or biochemical pregnancies (positive serum hCG but no ultrasound evidence of an intrauterine sac). The site of a "pre-clinical" pregnancy can never be verified and may in part have been due to early tubal pregnancies. The incidence of clinical miscarriage in the bacterial vaginosis group was no different to the normal normal flora group (6.5 versus 7.5% respectively). Our own study of 301 patients similarly showed no difference in the rate of clinical pregnancies miscarrying2. Reference to the implantation rates in the respective groups would have been helpful, particularly as the authors suggest pre-existing endometritis may reduce embro implantation and cause miscarriage. We found no difference in embryo implantation rates comparing patients with bacterial vaginosis to normal flora (15.8 versus 15.5% respectively)2. Hydrosalpinx is associated with a significantly reduced embryo implantation3 and significantly higher rates of spontaneous abortion4. Daya, in a meta-analysis of 35 studies including 16 523 treatment cycles, showed a near doubling of the miscarriage rate (Odds Ratio 1.83 , CI 1.39-2.42) with hydrosalpinx4. Ralph et al's study1 did not take into account this important potential confounding factor. Further, we observed a strong correlation between tubal infertility and the incidence of bacterial vaginosis at the time of IVF2. It is premature to consider an intervention study treating bacterial vaginosis during early embryo development before confirming that significantly lower embryo implantation rates exist in the bacterial vaginosis group. Furthermore, it would be helpful to reanalyse the data with respect to tubal infertility and hydrosalpinx as the apparent differences in miscarriage rates may be explained by a higher proportion of the bacterial vaginosis group having this abnormality. Bacterial vaginosis may simply be a marker for hydrosalpinx - this will not be affected by drug intervention. Neil H Liversedge Clinical Research Fellow Stephen D Keay Clinical Research Fellow Julian M Jenkins Consultant/Senior Lecturer Department of Obstetrics and Gynaecology, University of Bristol, St Michael's Hospital, Bristol BS2 8EG. References 1 Ralph SG, Rutherford AJ, Wilson JD. Influence of bacterial vaginosis on conception and miscarriage in the first trimester. BMJ 1999; 319:220-3. (24 July) 2 Liversedge NH, Horner P, Turner A, Keay SD, Jenkins JM, Hull MGR. The influence of bacterial vaginosis on in vitro fertilisation and embryo implantation during IVF-ET treatment. Hum Reprod 1999;14:2410-4. 3 Fleming C, Hull MGR. Impaired implantation after in vitro fertilisation treatment associated with hydrosalpinx. Br J Obstet Gynecol 1996;103:268-72. 4 Daya S. Proceedings of 43rd annual meeting of the Canadian Fertility and Andrology Society 1997 in Niagara-on-the-Lake, Ontario, Canada.