The LADY study: epidemiological characteristics of prevalent and new genitourinary syndrome of menopause cases in Greece.

OBJECTIVE: The genitourinary syndrome of menopause (GSM) is often underdiagnosed and undertreated despite its significant impact on postmenopausal quality of life. We assessed the prevalence of GSM and associated symptoms in Greek perimenopausal/postmenopausal women attending gynecology clinics. METHODS: Four hundred and fifty women, aged 40-70 years (93.1% postmenopausal), attending three gynecology clinics at university hospitals completed a validated questionnaire and underwent pelvic examination. RESULTS: GSM was diagnosed in 87.6% of the women at the study visit, whereas only 16% of the overall sample had been previously diagnosed with the condition. Vaginal dryness (72.7%), vulvar burning sensation or itching (58.0%) and dyspareunia (52.7%) were the most prevalent symptoms. Pelvic signs consisted of vaginal dryness (89.1%), loss of vaginal rugae (80.6%) and vulvovaginal pallor (86.9%). However, only 31.3% of the participants had discussed genitourinary symptoms with their health-care professionals (HCPs). Regarding management, only 11.1% of women had prior experience with any form of therapy, and currently only 8.7% were receiving treatment. CONCLUSION: GSM is highly prevalent in this Greek perimenopausal/postmenopausal population. Nevertheless, the majority of women remain undiagnosed and untreated. Education for both women and HCPs regarding GSM will lead to improved diagnosis and better management of this syndrome.

Vaginal laser therapy for GSM/VVA: where we stand now - a review by the EUGA Working Group on Laser.

Vulvovaginal atrophy (VVA) is a chronic progressive condition that involves the genital and lower urinary tracts, related to the decrease of serum estrogenic levels when menopause occurs. The definition of genitourinary syndrome of menopause (GSM) is a medically more accurate, all-encompassing and publicly acceptable term than VVA. Due to the chronic progressive trend of GSM, symptoms tend to reappear after the cessation of therapy, and frequently long-term treatment is required. First-line therapies include vulvar and vaginal lubricant or moisturizers, and, in the case of failure, low-dose vaginal estrogens are the preferred pharmacological therapy. Populations of patients, such as breast cancer (BC) survivors, are affected by iatrogenic GSM symptoms with concerns about the use of hormonal therapies. The non-ablative erbium:YAG laser and the fractional microablative CO2 vaginal laser are the two main lasers evaluated for GSM treatment. The aim of this comprehensive review is to report the efficacy and safety of Er:YAG and CO2 vaginal lasers for GSM treatment. Vaginal laser therapy has been demonstrated to be effective in restoring vaginal health, improving VVA symptoms and sexual function. The data suggest that both Er:YAG and CO2 vaginal lasers are safe energy-based therapeutic options for management of VVA and/or GSM symptoms in postmenopausal women and BC survivors.

Can pelvic organ prolapse in postmenopausal women be treated with laser therapy?

PURPOSE: This study aims to assess the effectiveness of the non-ablative photothermal erbium laser (Er:YAG laser) for managing anterior and/or posterior vaginal compartment prolapse. METHODS: A randomized, single-blind, 1:1 trial was performed comparing Er:YAG laser treatment to watchful waiting in postmenopausal women with symptomatic cystocele and/or rectocele stage 2 or 3 who opted to undergo surgery due to bothersome prolapse symptoms. Three Er:YAG laser treatments at monthly intervals were applied for the Er:YAG laser group, while there was no treatment for the watchful-waiting group. The primary outcome was the proportion of patients with stage 0 or 1 following laser treatment, while secondary outcomes included the Pelvic Organ Prolapse Quantification System (POP-Q points), Pelvic Floor Distress Inventory Questionnaire short-form, Pelvic Floor Impact Questionnaire short-form, and Patients Global Impression of Improvement (PGI-I). All outcomes were evaluated at baseline and 4 months post baseline. RESULTS: Thirty women (15 vs. 15) were eligible to be included. No participants (0%) in either group had POP-Q stage 0 or 1 at 4 months. Moreover, no change was present in the secondary outcomes. In the PGI-I, 2/15 (14%) and 0/15 (0%) participants declared much better/very much better in the laser and watchful-waiting group, respectively. CONCLUSIONS: The findings of this study do not support use of the intravaginal Er:YAG laser for treatment of the anterior/posterior vaginal wall. Clinical trial identification number: NCT03714607.

CO2 laser and the genitourinary syndrome of menopause: a randomized sham-controlled trial.

PURPOSE: This study aimed to clarify the efficacy of intravaginal CO2-laser treatment in postmenopausal women with genitourinary syndrome of menopause (GSM). MATERIALS AND METHODS: This double-blind, randomized, sham-controlled trial included postmenopausal women diagnosed with GSM and bothersome dryness and dyspareunia. Treatment consisted of three sessions. Active CO2-laser treatments (active group) were compared to sham treatments (sham group) with the primary endpoints being changes in dryness and dyspareunia intensity, as assessed by the 10-cm visual analog scale. Secondary endpoints were as follows: changes in Female Sexual Function Index (FSFI; total score and all domains), itching, burning, dysuria, and Urogenital Distress Inventory (UDI-6); incidence of symptoms; and presence of adverse events. All outcomes were evaluated at baseline and 4 months post baseline. RESULTS: Fifty-eight women (28 in the active group and 30 in the sham group) were eligible for inclusion. In the active group, dryness, dyspareunia, FSFI (total score), itching, burning, dysuria, and UDI-6 were significantly improved (mean [standard deviation] -5.6 [2.8], -6 [2.6], 12.3 [8.9], -2.9 [2.8], -2.3 [2.8], -0.9 [2.1], and -8.0 [15.3], respectively). In the sham group, dryness, itching, and burning were significantly improved (-1.9 [2], -1.4 [1.9], and -1 [1.9], respectively). All changes were in favor of the active group. After completion of the protocol, the proportion of participants with dryness, dyspareunia, and sexual dysfunction was significantly lower in the active group compared to those in the sham group (all p < 0.005). CONCLUSIONS: CO2 laser could be proposed as an effective alternative treatment for the management of GSM as it is superior to sham treatments.

Adenomyosis: Disease, uterine aging process leading to symptoms, or both?

For many decades adenomyosis has been a histological diagnosis in hysterectomy specimens. Traditionally, it has been considered a disease of late reproductive and premenopausal years causing uterine enlargement, dysmenorrhoea and menorrhagia. Recent advances in pelvic and uterine imaging techniques including transvaginal sonography and magnetic resonance imaging were responsible for a shift towards a non-invasive diagnosis and made a significant contribution to a better understanding of its pathogenesis, epidemiology, histological spectrum, and clinical symptomatology. With these non-invasive tools it has been shown that adenomyosis is probably a condition affecting much younger populations and is frequently asymptomatic at an early stage of its development. Regarding symptomatic disease, the distribution and extent of adenomyotic lesions do not correlate consistently with the various symptoms that are considered typical of adenomyosis. More importantly, accurate diagnosis of adenomyosis suffers from a lack of consensus among experts on imaging and even histological diagnostic criteria. Several pathogenetic theories have attempted to shed light on the establishment, evolution and distribution of adenomyotic lesions within the uterine wall, including the tissue injury and repair (TIAR) mechanism, metaplasia, and the more recent genetic-epigenetic theory. So far, none of these can adequately and independently explain the appearance of all types of adenomyosis. This review paper attempts a correlation between the proposed pathogenetic theories and the clinical and histological spectrum of adenomyosis, in an effort to give a plausible explanation of the evolution of this condition from an asymptomatic state to a disease, through synthesis of the existing data.

A study protocol of vaginal laser therapy in gynecological cancer survivors.

Objectives: Sexual dysfunction and radiation cystitis are common adverse events following radiotherapy for gynecological cancer (GC). This study aims to assess the efficacy of intravaginal CO2 laser on GC survivors with dyspareunia following pelvic radiation and/or brachytherapy.Methods: This is the study protocol of a randomized double-blind placebo-controlled trial. All participants will receive five therapies (active or placebo) at monthly intervals. Outcomes will include a 10-cm visual analog scale measuring dyspareunia, vaginal dryness, and other symptom intensity, 3-day voiding diary, Day-to Day Impact of Vaginal Aging questionnaire, Female Sexual Function Index, European Organization for Research and Treatment of Cancer Quality of Life questionnaire cervical cancer module, Urogenital Distress Inventory short form, King's Health Questionnaire, International Consultation on Incontinence Questionnaire short form/female lower urinary tract symptoms, patient perception of improvement, sexual satisfaction of male partners, vaginal maturation value, and Vaginal Health Index. Differences between groups will be assessed at baseline and 1, 3, 6, 9, and 12 months following the five laser therapies.Results: As this is a study protocol, the study is ongoing with an expected end of recruitment and analysis date of 2021.Conclusion: Pelvic radiotherapy for GC increases the 5-year survival rate but with a negative impact on women's quality of life due to sexual dysfunction and radiation cystitis onset. With this study, CO2 laser therapy will be evaluated for the first time in GC survivors treated with radiotherapy. ClinicalTrials.gov registration number: NCT03714581.

Rationale and design for fractional microablative CO2 laser versus photothermal non-ablative erbium:YAG laser for the management of genitourinary syndrome of menopause: a non-inferiority, single-blind randomized controlled trial.

Genitourinary syndrome of menopause (GSM) is a common condition affecting up to 50% of postmenopausal women and up to 70% of postmenopausal breast cancer survivors. GSM is a chronic condition with a significant impact on sexual health and quality of life. The mainstay of treatment has been with symptomatic relief using topical emollients or lubricants. Second-line treatment is with topical vaginal estrogens to restore the physiology of the vaginal epithelium. For some, the latter is not suitable or acceptable. Newer treatments with ospemifene and vaginal lasers have now been introduced. The two main types of laser currently used for the treatment of GSM are the fractional microablative CO2 laser and the non-ablative photothermal erbium:YAG laser. We present a study protocol for a multicenter, prospective, non-inferiority, single-blinded, randomized controlled trial comparing the fractional microablative CO2 laser versus the photothermal non-ablative erbium:YAG laser for the management of GSM. We will recruit 88 postmenopausal women across two sites who will be randomized to one of the two laser groups. Participants will all have GSM symptoms and a Vaginal Health Index Score < 15. All participants will receive an active treatment. Each participant will receive three applications of vaginal laser 1 month apart and will be followed up at 1 month, 6 months, and 12 months. Our primary outcomes will look at all changes of GSM symptoms (dryness, dyspareunia, itching, burning, dysuria, frequency, urgency), urinary incontinence (if present), and overall sexual satisfaction. Both subjective and objective means will be used to assess participants. The findings of this trial have the potential to allow clinicians and women suffering from GSM to make an informed decision when opting for a specific laser type. The trial will add to the current growing body of evidence for the safe use of vaginal lasers in GSM as an alternative treatment. We hope this trial will provide robust and long-term data for the safe use of both lasers.

Investigation of pelvic floor disorders.

Pelvic floor disorders (PFDs) are a common and complex problem encompassing a broad spectrum of conditions such as urinary incontinence, voiding difficulties, pelvic organ prolapse, anal incontinence, and chronic pelvic pain. The initial assessment of women with PFDs is based on a detailed and focused history and a holistic clinical evaluation of the pelvic floor. Other investigations may be used in clinical practice for the determination of the pathophysiology and the severity of the PFDs. In the field of urogynecology, urodynamic studies, ultrasound, and magnetic resonance imaging of the pelvic floor are currently implemented in the diagnostic work-up of women with PFDs. These provide valuable information not only on the anatomic integrity but also on the function of the pelvic floor which may not be apparent from the clinical examination. The provision of such information is complementary to the patient's symptoms and degree of bother and enables the implementation of a targeted treatment plan, thus maximizing the likelihood of cure and minimizing the risk of treatment complications.

The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women.

OBJECTIVES: To assess the effect of microablative fractional CO2 laser (MFCO2-Laser) therapy on the vaginal microenvironment of postmenopausal women. METHODS: Three laser therapies at monthly intervals were applied in postmenopausal women with moderate to severe symptoms of genitourinary syndrome of menopause, pH of vaginal fluid >4.5 and superficial epithelial cells on vaginal smear <5%. Vaginal fluid pH values, fresh wet mount microscopy, Gram stain and aerobic and anaerobic cultures were evaluated at baseline and 1 month after each subsequent therapy. Nugent score and Hay-Ison criteria were used to evaluate vaginal flora. RESULTS: Fifty-three women (mean age 57.2 ± 5.4 years) participated and completed this study. MFCO2-Laser therapy increased Lactobacillus (p < 0.001) and normal flora (p < 0.001) after the completion of the therapeutic protocol, which decreased vaginal pH from a mean of 5.5 ± 0.8 (initial value) to 4.7 ± 0.5 (p < 0.001). The prevalence of Lactobacillus changed from 30% initially to 79% after the last treatment. Clinical signs and symptoms of bacterial vaginosis, aerobic vaginitis or candidiasis did not appear in any participant. CONCLUSION: MFCO2-Laser therapy is a promising treatment for improving the vaginal health of postmenopausal women by helping repopulate the vagina with normally existing Lactobacillus species and reconstituting the normal flora to premenopausal status.

Prevalence and treatment of aerobic vaginitis among non-pregnant women: evaluation of the evidence for an underestimated clinical entity.

We sought to evaluate the evidence on the prevalence of aerobic vaginitis (AV) among symptomatic non-pregnant women, as well as the treatment administered for this clinical entity. The PubMed and Scopus databases were systematically searched. Sixteen studies met the inclusion criteria, 11 of which reported on the prevalence of possible AV, two on the prevalence of diagnosed AV, and three on the treatment and outcomes of women with diagnosed AV. The prevalence of diagnosed AV varied from 5 to 10.5 %. Streptococcus spp., Staphylococcus aureus, and coagulase-negative staphylococci were the most commonly identified Gram-positive pathogens among women with possible AV, with prevalences of up to 58.7, 41.7, and 37.4 %, respectively, while Escherichia coli was the most common Gram-negative pathogen identified, with a prevalence of up to 23 % among symptomatic women. Regarding antibiotic treatment for AV, the antibiotic schemes administered, which mainly consisted of suppositories of aminoglycosides, showed good effectiveness without serious adverse events provided by any of the included studies. The currently available data suggest that the prevalence of AV is not negligible, while the prevalence of possible AV is considerable. Well-designed studies comparing the prevalence of aerobic pathogens between symptomatic and asymptomatic women are warranted.

Magnifying lenses assisted nerve-sparing radical hysterectomy and prevention of nerve plexus trauma.

The objectives of the study were to present a new approach for nerve-sparing radical hysterectomy (NSRH) with the assistance of magnifying lenses and to describe the differences in autonomic nerve plexus trauma between NSRH type III and conventional radical hysterectomy (RH) types II and III with the aid of immunohistochemistry. Eighteen women with FIGO stage IB(1)-IB(2) cervical cancer underwent loupes-assisted NSRH (n = 8), RH type II (n = 6), and RH type III (n = 4). Biopsies were taken intraoperatively from uterosacral ligament (USL) and cardinal ligament (CL), as well as from anterior vaginal wall (AVW) and posterior vaginal wall (PVW). Immunohistochemistry was approached with the use of S-100 protein, a general nerve marker. The percentage area of immunoreactivity (PAI) was used as an objective quantitative measure of nerve fibers within the ligaments. The PAI was greater in RH-III biopsies from both USL and CL (P < 0.001) when compared with RH-II and NSRH biopsies. For AVW and PVW, PAI differences were not statistically significant (AVW, P = 0.119; PVW, P = 0.067). Uterine-supporting ligaments represent a major pathway for autonomic nerves to the pelvic organs. As significantly more autonomic nerves are transected during the division of the uterine-supporting ligaments in RH type III, a more careful approach in the dissection of the ligaments through nerve-preserving techniques seems to be necessary in order to prevent iatrogenic intraoperative injury of the pelvic plexus and reduce or prevent postoperative complications.

Probiotics for the treatment of women with bacterial vaginosis.

This review considers whether probiotics are effective agents for the treatment and/or prevention of bacterial vaginosis (BV). There seems to be an association between the absence of, or low concentrations of, vaginal lactobacilli and the development of BV. Many studies have suggested that the presence of H2O2-producing vaginal lactobacilli may protect against BV, although some studies do not support this hypothesis. In-vitro studies have suggested that certain specific strains of lactobacilli are able to inhibit the adherence of Gardnerella vaginalis to the vaginal epithelium and/or produce H2O2, lactic acid and/or bacteriocins, which inhibit the growth of bacteria causing BV. Clinical trials showed that intra-vaginal administration of Lactobacillus acidophilus for 6-12 days, or oral administration of L. acidophilus or Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 for 2 months, resulted in the cure of BV (defined as a 0-1 positive score according to Amsel's criteria), and/or reduced the recurrences of BV, and/or caused an increase in vaginal lactobacilli and restoration of a normal vaginal microbiota, significantly more frequently than did a placebo, acetic acid or no treatment. However, several trials have found no significant difference in the cure rate of BV and in the number of vaginal lactobacilli after intra-vaginal instillation of lactobacilli when compared with the effect of a placebo or oestrogen. Thus, although the available results concerning the effectiveness of the administration of lactobacilli for the treatment of BV are mostly positive, it cannot yet be concluded definitively that probiotics are useful for this purpose.

Direct imaging of the pelvic floor muscles using two-dimensional ultrasound: a comparison of women with urogenital prolapse versus controls.

OBJECTIVE: To evaluate the anatomy of the levator ani muscle in women with urogenital prolapse versus matched controls without prolapse using real-time two-dimensional (2-D) ultrasound. DESIGN: Prospective observational study. SETTING: Tertiary referral urogynaecology unit. POPULATION: Forty-three women with pelvic organ prolapse (POP) and 24 women (controls) attending a gynaecology clinic without prolapse. METHODS: All participants completed a standardised symptom questionnaire. MAIN OUTCOME MEASURES: The morphology of the vagina and paravaginal tissue was recorded at different levels. The thickness of the levator ani and the hiatal area were measured at rest. Reproducibility of the method was assessed by repeated measurements to assess intra-observer variability and inter-observer variability. RESULTS: This method showed good intra-observer and inter-observer reproducibility and reliability. In controls, the pubococcygeus muscle showed more regular echogenicity with no evidence of trauma, whereas in women with prolapse the muscle had mixed echogenicity. (P = 0.002). The mean thickness of the pubococcygeus did not differ between groups. The levator hiatal area was significantly larger in women with pelvic floor prolapse versus controls (17.8 cm2 versus 13.5 cm2, P < 0.001). This increase in hiatal area positively and significantly correlated with prolapse severity (P < 0.001). CONCLUSIONS: Morphology and hiatal area can be reliably imaged using 2-D ultrasound. Prolapse was related to changes in pelvic floor morphology and increased levator hiatal area. The use of 2-D ultrasound provides an important insight into the pathophysiology of prolapse.

Imaging the urethral sphincter with three-dimensional ultrasound.

OBJECTIVE: To image the striated urethral sphincter (rhabdosphincter) using three-dimensional ultrasound and to compare its size in women with genuine stress incontinence and continent controls. METHODS: Women with no previous continence or prolapse surgery had transvaginal sonography using a 7.5-MHz mechanical sector endoprobe with real-time and three-dimensional facilities. Three perpendicular planes were displayed simultaneously on the screen. Manipulation of the stored images allowed detailed morphologic assessment of the urethra at different levels using several parallel cross-sectional planes along its length. The length, thickness, and volume of the rhabdosphincter were measured. RESULTS: Forty-six women with genuine stress incontinence (27-73 years, mean 48) and 48 continent controls (23-76 years, mean 49) were studied. In the transverse plane, the inner part of the urethra, which consists of urothelium and smooth muscle, appeared hyperechogenic compared with the outer hypoechogenic ring of striated muscle. The two groups studied were not different in age and parity. Women with genuine stress incontinence, compared with continent controls, had a significantly shorter (mean +/- standard deviation 16.9 +/- 1.9 mm compared with 19.2 +/- 3.6 mm; P = .001), thinner (2.1 +/- 0.5 mm compared with 2.5 +/- 0.4 mm; P < .001), and smaller volume (0.8 +/- 0.2 mL compared with 1.2 +/- 0.2 mm; P < .001) of the striated urethral sphincter. There was a close correlation between the urethral sphincter volume and the degree of incontinence assessed on videocystourethrography (r = -.65, P < .001). CONCLUSION: Three-dimensional ultrasound allowed examination of the female urethra in planes that could not be visualized by conventional sonography. The rhabdosphincter had a smaller volume in women with genuine stress incontinence than in continent women.

The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo.

Tamoxifen (tam) is used extensively for treatment of patients with breast cancer and is being evaluated for chemoprevention in healthy women. It has, however, been reported to increase the risk of endometrial cancer in post-menopausal women, probably by an oestrogenic effect on the endometrium. It also causes endometrial cysts and polyps. The aims of this study were to identify the incidence of endometrial thickening, polyps and cysts by transvaginal ultrasound (TVUS) screening of a population of post-menopausal healthy women in the Royal Marsden tamoxifen chemoprevention trial and to evaluate the possible benefit from the use of intermittent norethisterone (NE) in women with persistent changes. Since 1990, we have undertaken regular TVUS, using an endovaginal B mode probe, of the 463 post-menopausal women in the trial randomized to tam (20 mg day(-1)) or placebo (plac), without breaking the randomization code. Endometrial thickening (ET) was defined as > or = 8 mm at the widest point across the myometrial cavity in the longitudinal plane, including any stromal changes. Cystic changes were defined as more than one hypoechogenic area > 1 mm. Polyps were identified using saline hydrosonography. Oral NE (2.5 mg day(-1)) was used for 21 days out of 28 for three consecutive cycles by women with persistent endometrium > or = 8 mm, including cystic and polypoid changes. TVUS was repeated after the three courses to evaluate any change caused by NE and endometrial biopsies, including hysteroscopy, was performed on those women with persistent abnormalities. A persistent ET > or = 8 mm was identified in 56 (24%) of the 235 women on tamoxifen compared with only 5 (2%) of 228 women on placebo (P <0.0005). Stromal changes, including cysts, were detected in 36 (15%) and polyps in 26 (11%) of the women on tamoxifen compared with only two (< 1%) of the women on placebo (P << 0.0005). After 3 months of cyclical norethisterone, 39 of 47 women (83%) on tamoxifen had persistent ultrasound changes. However, 45 (96%) had a progesterone withdrawal bleed. Hysteroscopy was performed in 39 women on tamoxifen (28 endometrial biopsy, 15 polypectomy), five of whom had histological evidence of a proliferative endometrium and a further three had an atypical hyperplastic endometrium (one of whom had a focus of invasive carcinoma). The cysts and polyps which were detected in women on tam could not be reversed by NE and were presumably stromal and not of malignant risk. However, 96% of the women had withdrawal NE bleeding, indicating an oestrogenically primed endometrium which could be a mechanism for an increased risk of endometrial cancer. Further studies are required to ascertain whether a progestin would protect against this risk. As in other studies, these results indicate that any increased risk of endometrial cancer caused by tamoxifen is low, and that TVUS screening is probably not justified for asymptomatic women on tamoxifen.

Effects of indomethacin on follicular structure, vascularity, and function over the periovulatory period in women.

OBJECTIVE: To assess the effect of indomethacin (taken at defined times) on follicular rupture, indexes of intrafollicular blood flow, and steroidogenesis. PARTICIPANTS: Six healthy volunteers awaiting treatment for infertility by IVF-ET during subsequent natural cycles. INTERVENTIONS: All women were examined (at least every 8 hours) by transvaginal ultrasonography with color Doppler imaging and had samples of blood taken for hormone analysis. A self-test for urinary LH was performed before each scan. Indomethacin was first taken (50 mg three times per day) according to the maximum follicular diameter (first four women) or when the LH dipstick gave a positive result; the drug was taken for > or = 3 days. RESULTS: Follicular rupture was delayed in five of six cases (by 2 to 12 days). There was a reduction in intrafollicular peak systolic velocity before and after the positive urinary LH test compared with historical controls. Three follicles (50% of women) with the highest peak systolic velocity had an hemorrhagic appearance and persisted longer. There was no significant effect on menstrual cycle length or the levels of circulating FSH, E2, LH, or P. CONCLUSION: Indomethacin administered at the time of a positive self-test for urinary LH can delay follicular rupture with an associated reduction in intrafollicular blood flow but with no apparent effects on hormonal or menstrual status.

Umbilical cord blood erythroblast count as an index of intrauterine hypoxia.

The relation of umbilical cord blood arterial pH, Apgar score, leucocyte count, and erythroblast count at delivery with the diagnosis of fetal distress in labour was studied prospectively in three groups of singleton pregnancies delivering at term vaginally (55 infants), by elective caesarean section (39 infants), or by emergency caesarean section for abnormal intrapartum fetal heart rate patterns (55 infants). In the emergency caesarean section group the umbilical cord blood arterial pH was significantly lower and the leucocyte and erythroblast counts were higher than in the elective caesarean section group. Comparison of the emergency caesarean section and spontaneous vaginal delivery groups showed significant differences for pH and erythroblast count, but not for leucocyte count. In the spontaneous vaginal delivery group erythroblastosis was associated with umbilical cord blood pH, whereas leucocytosis was associated with the length of labour. The five minute Apgar score was > or = 7 in all infants. This study suggests that leucocytosis is a non-specific response of the fetus to labour, whereas erythroblastosis reflects fetal tissue hypoxia.