UTEROTONICS IN PPH:

 Zubor P, Szunyogh N, Dokus K, Scasny P, Kajo K, Galo S, bringers K, Krivus S, Danko J. Dept. of Obst. ^ Gynecology, Jesseniou Faculty of Medicine, Comenius University, Kollarova- 2, 03601, Martin, Slovak Republic. (Arch Gynec Obst. 2009 Sept. 17. (Epub ahead of print)

 Application of uterotonic on the basis of regular ultrasonic, evaluation off the uterus prevents unnecessary surgical intervention in the postpartum period.

OBJECTIVE: Ultrasonographic evaluation of the postpartum uterus to prevent retained placental tissue complications is still a matter of debate, and it is difficult to interpret its necessity on the basis of previous studies. We hypothesized that the application of uterotonic on the basis of regular postpartum ultrasound scanning of the uterus may reduce the number of unnecessary curettages in a large unselected population.

METHODS: This was a cross-sectional observational study conducted among mothers (n=6,028) delivering at two different (secondary and tertiary) hospitals to analyze the benefit of postpartum uterine ultrasound for clinical implications, Women delivering at the secondary care unit (n=1,915) had no regular postpartum ultrasound scans in comparison to those delivering at the tertiary unit (n=4,113). On regular ultrasound scans, morphological findings in the uterine cavity were recorded. Upon the presence of an intrauterine hyperechogenic mass larger than 2 cm in diameter, mothers received a single dose of uterotonic (methylergometrin 0.2 mg or oxytocin 5 IU) intra muscularly and control sonography after 24 h. In case of intra uterine mass persistence and serious postpartum hemorrhage women underwent a surgical intervention. The management was similar at the secondary unit, but ultrasound scans were provided only when there was a clinical finding. All patients were followed-up 6 weeks after labor.

RESULTS: Women delivering at the secondary institution experienced a higher incidence of puerperal surgical interventions (1.51 vs. 0.87%) and lower agreement between sonography and histological findings (72.4 vs. 86.1%) compared with women delivering at the tertiary care unit. Respectively (P<0.05), where the general incidence of interventions was 1.10% after spontaneous and 0.19% after cesarean deliveries. In addition, trained sonographer reached only 13.9% false-positive ultrasound scans. Time-dependent regression analysis of uterine morphological involution variables showed a significant association between uterine length, width, uterine cavity and cervical channel mass, P<0.0001, P<0.01, P<0.05, P<0.05, respectively, and insignificant association between uterine cavity volume with an increased time period postpartum.

(CONCLUSTIONS: In this study, routine ultrasound evaluation of the uterus in the postpartum period with regular application of uterotonic decreased the rate of surgical interventions. We strongly advise the introduction of postpartum uterine scanning into obstetrical practice, most suitably provided around day 3 after delivery. )

SURGERY IN PPH:

(Chen CY. Wang KG. Dept. of Obst. & Gynec, Mackay Memorial Hospital, Taipei, Taiwan.

BACKGROUND: Hemostatic square suturing is a useful technique for postpartum hemorrhage, but some complications may occasionally occur.

Case: A 36, year-old pregnant woman with placenta previa and percreta at 35 weeks, gestation complicated with massive vaginal bleeding. An emergency cesarean section was performed, and placenta previa with percreta and uterine atony were noted. A hemostatic square suture was placed to compress the uterus and stopped the hemorrhage successfully. The estimated blood loss was approximately 2,200 mL Thirty seven days after operation, massive vaginal bleeding developed and the ultrasonography showed a 6.84 x 5.71-cm complex intrauterine mass. The patient was treated with intra venous oxytocin, rectal Misoprostol, and blood transfusion. The beta-human chorionic gonadotropin levels returned to normal level on day 70 postoperatively, and ultrasonography revealed no obvious intra uterine mass.

(CONCLUSIONS: Late postpartum hemorrhage may result from the use of hemostatic square suture technique.

ROLE OF IMAGING IN PPH:

Imaging and diagnosis of postpartum complications: sonography and other imaging modalities. (Kamaya A, Ro K, Benedetti NJ, Chang PL, Desser TS. Stanford University Medical Center, Palo Alto, CA-94304, USA. ) Ultrasound Q. 2009 Sept, 25(3):151-62.

Postpartum complications can be broadly divided into 4 categories: postpartum hemorrhage, obstetrical trauma, thromboembolic complications, and puerperal infections. Postpartum hemorrhage is most commonly caused by uterine atony, abnormal placentation, or genital tract trauma. Secondary causes of hemorrhage include retained products of conception and, rarely, sub involution of the placenta implantation site. Uterine dehiscence or rupture may be occult on ultrasound examination and may be better visualized on sagittal computed tomography or magnetic resonance imaging. Obstetric trauma during prolonged vaginal or cesarean delivery may lead to fistula formation, urethral injury, or bowel injury. Later potential complications of cesarean delivery include cesarean delivery scar, and placenta accreta.

Thromboembolic complications can include pulmonary embolism and deep vein thrombosis as well as ovarian vein thrombosis, the latter of which can be difficult to clinically differentiate from appendicitis in the postpartum female.

ROLE OF SURGERY IN PPH:

Are ultrasonographic myoma characteristics associated with blood loss at delivery?

(Andreani M, Vergani P, Ghidini A, Locatelli A, Ornagi S, Pezzullo JC. Dept. of Obst. & Gynec. University of Milano-Bicocca, Monza, (Ultrasound Obstet Gynecol. 2009 Sept. 34 (3): 322.5)

OBJECTIVES: The presence of myomas in pregnancy is associated with greater blood loss at delivery. The aim of this study was to evaluate whether the sonographic characteristics of myomas can predict blood loss at delivery in women with large myomas.

METHODS: Among women who underwent second-trimester ultrasound screening at out department between January 1996 and December 2004, 251 had at least one myoma with a mean diameter > or =5 cm. Number of myomas (single vs. multiple), maximum diameter of the largest myoma, sum of the maximum diameter of each myoma, change in size of myomas between first and last scan, and location in relation to the placenta and to the presenting part of the fetus ( above or below ) were analyzed relation to blood loss at delivery and severe postpartum hemorrhage ( > or= 1000 mL).

RESULT:; multivariate analysis showed that the presence of multiple myomas was the only parameter independently associated with amount of blood loss at delivery (P= 0.003). The association between the presence of multiple myomas and severe postpartum hemorrhage was of borderline significance for the statistical power of this study (P=0.08).

(CONCLUSIONS: In women with large myomas, the presence of multiple tumors is independently associated with heavier blood loss at delivery but not with postpartum hemorrhage of > or = 100 mL)

Saliva test to identify women at risk of delivering early

An exploratory study to be published in BJOG, has shown that women going into early preterm labour (before 34 weeks gestation) have low-levels of progesterone in their saliva as early as 24 weeks, and that moreover, these levels fail to rise during pregnancy in the normal way. This offers the possibility of developing a simple, non-invasive test to identify women at increased risk of delivering early. Progesterone is a hormone which helps regulate the menstrual cycle; but perhaps most importantly, it is the primary hormone of pregnancy.

Researchers at University College London and King’s College London, collected specimens of saliva from 92 women taking part in an existing randomized control trial (the PREMET study) of preventive treatment for preterm birth. Women recruited to the study all had an increased risk of having a preterm birth (they were selected based on having at least one risk factor such as a history of previous preterm birth, late miscarriage etc). Saliva samples were taken from these women every week from 24 weeks gestation until 34 weeks or delivery (whichever was the sooner), and analyzed. Women were divided into three groups: delivery before 34 weeks, delivery between 34 – 37 weeks and delivery at term (after 37 weeks).

The results show that the concentration of progesterone in the saliva of women delivering after spontaneous labour before 34 weeks was significantly lower than those giving birth at term (after 37 weeks) at all gestational ages from 24 weeks onwards. The authors note that progesterone is known for its anti-inflammatory properties, and suggest that low levels of the hormone in the maternal body could contribute to bacterial infection, a recognized cause of early preterm labour. Based on their findings, researchers believe saliva progesterone could be a useful predictor of early preterm labour and delivery.

This promising study, though small, suggests that salivary progesterone measurement could provide a useful early identification of women with an increased chance of an early premature birth. Further prospective research is needed on a larger cohort. Finding a reliable marker of impending preterm birth would allow us to try and develop targeted preventative measures.

Ref: British Journal of Obstetrics and Gynecology, 07/22/09

Premature Rupture of Membranes

The Centers for Disease Control and Prevention’s updated interim guidelines on preventing and treating swine flu in pregnancy, reprinted below, offer sound advice. Premature rupture of membranes (PROM) is defined as rupture of membranes before the onset of labor. Preterm PROM occurs before 37 weeks of gestation. The etiology of spontaneous PROM is not known; however, it is often suggested that uterine contractions (frequently undetected by the patient) result in cervical change and that an intense inflammatory reaction of the chorioamnion leads to rupture.

The latent period is the interval between membrane rupture and the onset of labor. Generally, the earlier in gestational age that rupture of membranes occurs, the longer the latent period. More than 90% of patients with PROM begin labor within 24 hours.In pregnancies of less than 37 weeks of gestation, preterm birth (and its sequelae) and infection are the major concerns after PROM.

Diagnosis

The patient's history alone is correct in more than 90% of patients. Digital examination of patients who are not in labor and for whom induction is not planned should be avoided because such examinations add no useful information and probably increase the risks for infection. Sterile speculum examination should be undertaken to confirm the diagnosis; evaluate the general appearance of the cervix; take appropriate samples for cultures, such as for Streptococcus agalactiae, C trachomatis, and N gonorrhoeae; and rule out prolapse of the umbilical cord.

Confirmation of the diagnosis consists of identifying a pool of fluid and testing for an alkaline pH with an appropriate indicator. A swab from the posterior fornix should be smeared on a slide, allowed to dry, and checked under a microscope for a typical ferning appearance, indicating amniotic fluid. When the diagnosis of PROM is confirmed, the gestational age should be assessed and the patient should be carefully evaluated for evidence of labor, chorioamnionitis, or nonreassuring fetal status.

Management: After admission and evaluation to exclude infection and fetal distress, management depends on gestational age. Based on these factors and individual circumstances, management in the hospital or with selected patients at home with careful observation is feasible.

TERM

At 36 weeks of gestation and beyond, delivery is the ideal management of PROM. Patients in active labor should be allowed to progress and be managed like other term patients

26-35 WEEKS

Because the major risks to the baby after preterm PROM are related to prematurity, management is directed toward prolonging gestation when there is no labor, no infection, and no evidence of cord compression on antenatal FHR testing. Clinical parameters, including symptoms, vital signs, uterine tenderness, and odor of the lochia, are monitored. An ultrasound examination should be performed to determine fetal age and lie and to detect oligohydramnios.

In patients with a positive cervicovaginal culture for group B streptococci or gonococci, however, it is appropriate to treat with antibiotics. Use of intrapartum penicillin during labor in group B Streptococcus-positive women with preterm PROM decreases neonatal sepsis. Recent evidence suggests that prophylaxis with antibiotics in cases of preterm PROM is also of benefit to women with negative cultures because it has been shown to prolong pregnancy and decrease morbidity.

 In the presence of ruptured membranes, the fetus is at risk from umbilical cord compression, even in the absence of labor. Continuous FHR monitoring in the initial assessment of the patient should be followed by frequent evaluation, such as daily antepartum FHR assessments. Corticosteroids are recommended to accelerate fetal pulmonary maturity.

Another option is to evaluate the fetus for pulmonary maturity and to expedite delivery if maturity is documented.

LESS THAN 25 WEEKS

In patients with PROM at less than 25 weeks of gestation, there is a relatively low likelihood (approximately 40%) that a viable gestational age will be achieved. Even in patients whose infants do survive, many of the babies suffer significant short- and long-term morbidity, including pulmonary hypoplasia, facial deformity, and limb contractures and deformities. If the gestational age is early and the patient elects to terminate her pregnancy, this option is reasonable and should be discussed. If the patient elects to continue the pregnancy, expectant management, even at home with a regimen of avoiding both coitus and douching, is reasonable. Delivery is indicated for chorioamnionitis.

Ref: Eleanor J. Rutherford, Journal of Obstetrics and Gynecology, July 2009, Volume 25298, Number 17, pp. 4392-4655

Effects of L-carnitine on Infertile Men’s Spermiogram; a Randomized Clinical Trial

 (Jr Of Reproduction And Fertility: Volume 10, Issue 4, Year 2010, Number 41)

 • Sepideh Peivandi (M.D.) Department of Obstetrics and Gynecology, Faculty of Medicine, Mazandaran University of Medical Sciences, Mazandaran, Iran

 • Abasali Karimpour (Ph.D.) Department of Anatomy and Embryology, Faculty of Medicine, Mazadaran University of Medical Sciences, Mazandaran, Iran

 • Narges Moslemizadeh (M.D.) Department of Obstetrics and Gynecology, Faculty of Medicine, Mazandaran University of Medical Sciences, Mazandaran, Iran

 Introduction: Male infertility is one of the most challenging problems in andrology. The common cause of male infertility is related to disorders in sperm production and its improvement is synonymous with better treatment outcomes. Although, the etiology of infertility is not clear in most cases but different treatment options have been suggested to increase sperm count and motility. L-carnitine, which is found in different food items and it is derived from lysine and methionine, is a substance essential for the oxidation of long-chain fatty acids in the mitochondria and protection of cell membranes from damages caused by free oxygen radicals. This study was done to evaluate the efficacy of L-carnitine in improving sperm quality in infertile men.

Materials and Methods: This double blind randomized cross-over, clinical trial was conducted on 30 infertile men attending Sari Imam Khomeini Hospital’s Infertility Clinic during 2005- 2006. Subjects that had at least two abnormal spermiogram, based on WHO criteria, with a two-week interval during four weeks and their gonadotrophins, testosterone an prolactin concentrations were within normal range were recruited for the study. The exclusion criteria were composed of individuals with medical conditions other than infertility such as grade 3 or 4 Varicocele, testicular atrophy, ejaculatory disorders, use of any medications in the past two months prior to the study, azoospermia, endocrinological disorders, ICSI candidacy for severe spermiogram abnormalities or other causes of infertility. The patients were randomly allocated to two groups of A and B. Group A and B received L-carnitine and placebo 2g/day for 8 weeks respectively. After a washout period of 8 weeks, the two groups, changed place and received placebo and L-carnitine (2g/day×8w). Sperm analyses were done in four stages: Before and after the first intervention, at the end of washout period and after the second intervention.

Results: There were significant improvements in mean sperm concentration and progressive sperm motility upon two months of L-carnitine intake (p<0.05) but no significant changes were found in sperm volume or morphology. The aforementioned changes retracted to the primary status after two months. No changes were seen following the intake of placebos in the cases.

Conclusion: L-carnitine intake effectively improved the mean sperm count and progressive sperm motility. However, confirmation of these results warrants more thorough clinical trials.

A Predictive Model for the Diagnosis of Preeclampsia

(Jr Of Reproduction And Fertility: Volume 10, Issue 4, Year 2010, Number 41)
 

" Elahe Allahyari (.M.Sc)

• Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

" Abbas Rahimi Foroushani (Ph.D.)

• Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

" Hojjat Zeraati (Ph.D.)

• Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

" Kazem Mohammad (Ph.D.)

• Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

" Ziba Taghizadeh (.M.Sc)

• Department of Midwifery, Faculty of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran

Introduction: Preeclampsia is one of the three main causes of death in pregnant women. The medical condition is identified by hypertension and proteinuria with serious effects on the health of mother and the fetus. There seems to be no precise methods to diagnose preeclampsia at its onset. This study was done to evaluate the simultaneous measurement of some variables thought to be responsible in the pathogenesis of preeclampsia for predicting or screening those at risk.

Materials and Methods: In this study, 466 primipara were selected randomly among the bulk of pregnant women who attended Maryam Hospital for prenatal care in Tehran, Iran during 2007-2008. The subjects had no history of chronic health conditions and regularly took Iron supplements. The predictive variables included age, job, education, income, number of pervious marriages, BMI during the first trimester of pregnancy, age at the time of recruitment for the study, changes in hematocrit concentration at the beginning and the 24th to 28th weeks of pregnancy, blood pressure and roll-over test during 28th to 32nd week of gestation but the onset of preeclampsia was considered as a dependent variable. For analyzing the overall effects of the mentioned variables on prediction of the disease, multivariate logistic regression analysis was employed and ROC curves were used for determining a suitable cut-off point for determining the sensitivity and specificity of the model.

Results: The prevalence of preeclampsia was 6.4% (95% CI: 4.2-8.6). Variables such as positive roll-over test, fulfillment of university education, marriage more than once, high blood pressure during the 24th-28th weeks of gestation, being a housekeeper, satisfaction with income, positive roll over test at a late stage of gestation and increase in BMI raised the risk of preeclampsia 8.61, 7.98, 2.65, 1.84, 1.56, 1.28, 1.21 and 1.11 times respectively. The proposed logistic regression model had a sensitivity of 83% and a specificity of 76% regarding the inclusion of all the mentioned variables.

Conclusion: Regarding the serious complications and negative effects of preeclampsia on both the mother and the fetus and the high sensitivity of this logistic regression model and imposition of no costs on the person for the measurement of the variables, this model seems to be suitable for the screening of preeclampsia.

Progesterone, Thyroid Hormone and Relaxin in the Regulation of the Invasive Potential of

Extravillous Trophoblasts in Early Placental Development

Takeshi Maruo, M.D., Ph.D.,

 Director, Kobe Children’s Hospital and Feto-Maternal Medical Center & Professor Emeritus, Kobe University,

Kobe, Japan

Placental tissues contain a heterogeneous population of cells, including villous cytotrophoblasts, syncytiotrophoblasts and extravillous trophoblasts (EVTs). EVTs are mainly uninuclear cells comprising all the trophoblastic elements located outside the villi. EVT has two distinct phenotypes, proliferative and invasive. The activity of the invasive EVTs is dependent on its apoptotic capacity and less on its proliferative potential. Apoptosis is an important determinant in regulating placental growth. Actually, apoptosis is more evident in the invasive EVTs than its proliferative counterpart and the extent of apoptosis is associated with augmented Fas and Fas ligand expression and reduced Bcl-2 protein expression (1).

The human early placenta is characterized by the invasion of EVTs to the decidua, leading to direct contact between EVTs and maternal blood. During the invasion process, EVTs express matrix metalloproteinase (MMPs), which are proteolytic enzymes that cleave all the constituents of the extracellular matrix. Although the controlled invasion of EVTs into the decidua is an essential process for early placental development and the maintenance of early pregnancy, the molecular mechanisms involved in EVT invasion to the decidua has been poorly understood In this editorial, the vital roles of progesterone, thyroid hormone and relaxin in the regulation of invasive potential of EVTs in early placental development are summarized on the basis of our recent studies.

 Progesterone in the Regulation of the Invasion of EVTs Clinically, progesterone (P4) is used in the treatment of threatened abortion, prevention of recurrent miscarriage and in the luteal support in assisted reproduction program. However, little is known about the molecular mechanism of P4 in the regulation of EVTs's function. P4 mediates its physiological effects through interaction with the PR, a transcription factor and a member of a large family of structurally related gene products known as the nuclear receptor super family. PR is expressed in multiple tissues as two isoforms, PR-A and PR-B. Our recent study revealed that PR-A and PR-B are present in HTR-8/SV neo cell line, which is a possible model of human EVTs (2). P4 inhibits apoptosis in the EVT cells by down-regulating Fas, Fas-ligand, caspase-3 and poly (ADP-ribose) polymerase (PARP) expression as well as up-regulating Bcl-2 expression in those cells. It seems that P4 may promote the invasion of EVTs to the decidua by inhibiting apoptosis of EVTs. This may explain the mechanism of P4 treatment on threatened abortion.

Thyroid Hormone in the Regulation of the Invasion of EVTs In clinical practice, maternal thyroid hormone deficiency has been implicated in early pregnancy loss, indicating that thyroid hormone is vital for the maintenance of early pregnancy. Actually, it became evident that T3 receptor mRNA (a 212-BP c-erbA?1 transcript) and protein are present in early placental EVTs (3). In cultured early placental EVTs, treatment with 3,5,3'-triiodothyronine (T3) reduced the expression of Fas and Fas-ligand as well as the cleavage of caspase-3 and PARP and suppressed apoptosis in those cells. Matrigel invasion assay revealed that T3 treatment remarkably increased the number of cell projections of EVTs over the membrane of Matrigel. Consistently, T3 treatment increased the expression of MMP-2, -3, fibronectin (FN) and integrina5β1 mRNA in the cultured EVTs (4). These findings suggest that T3 promotes the invasion of EVTs to the decidua by suppressing apoptosis and by up-regulating the expression of MMPs and integrin in early placental EVTs. This may explain the mechanism of thyroid hormone for the vital role in maintaining early pregnancy.

Relaxin in the Regulation of the Invasion of EVTs Although relaxin is known to promote softening of the uterine cervix and inhibits uterine contractility in rats, mice and pigs, little information is available about the role of relaxin in humans. In 2002, LGR7 and LGR8 were discovered to be receptors for relaxin. Actually, we have demonstrated for the first time the presence of relaxin receptors (LGR7 and LGR8) in the human early placental EVTs (5). In humans, three forms of relaxin have been identified; H1, H2, and H3 relaxin. H1 relaxin is present in the human decidua, placenta and prostate but not in the ovary, whereas H2 relaxin is present in the corpus luteum, placenta and decidua. H3 relaxin is mainly present in the brain. It seems that in humans, relaxin is both a systemic hormone secreted by the corpus luteum and an autocrine/paracrine hormone at the maternal-fetal interface formed by the decidua, placenta and fetal membranes. In our recent study to investigate the effects of recombinant H2 (rH2) relaxin on cultured early placental EVTs, treatment with rH2 relaxin increased MMP-2 and -9 mRNAs levels and decreased TIMP-1 mRNA levels in those cells (5). These results suggest that relaxin may promote the invasive potential of early placental EVTs by up-regulating MMP-2 and -9 expression and down-regulating TIMP-1 expression through the interaction with relaxin receptors (LGR7 and LGR8) in EVTs.

References

1. Murakoshi H, Matsuo H, Laoag-Fernandez JB, Samoto T, Maruo T. Expression of Fas/Fas ligand, Bcl-2 protein and apoptosis in extravillous trophoblast along invasion to the deciduas in human term placenta. Endocr J 2003; 50:199-207

2. Liu J, Matsuo H, Laoag-Fernandez JB, Xu Q, Maruo The effects of progesterone on apoptosis in the human trophoblast-derived HTR-8/SV neo cells. Mol Hum Reprod 2007; 13:869-874

3. Laoag-Fernandez JB, Matsuo H, Murakoshi H, Hamada AL, Tsang BK, Maruo T. 3,5,3'-Triiodothyronine down-regulates Fas and Fas ligand expression and suppresses caspase-3 and poly (adenosine 5'-diphosphate-ribose) polymerase cleavage and apoptosis in early placental extravillous trophoblasts in vitro. J Clin Endocrinol Metab 2004;89:4069-4077

4. Oki N, Matsuo H Nakago S, Murakoshi H, Laoag-Fernandez JB, Maruo T. Effects of 3,5,3'-triiodothyronine on the invasive potential and the expression of integrins and matrix metalloproteinase in cultured early placental extravillous trophoblasts. J Clin Endocrinol Metab 2004;89:5213-21 .

5. Maruo N, Nakabayashi K, Wakahashi S, Yata A, Maruo T. Effects of recombinant H2 relaxin on the expression of matrix metalloproteinase and tissue inhibitor metalloproteinase in cultured early placental extravillous trophoblasts. Endocrine 2007;32:303-310

 (Contributed By Dr. Maninder Ahuja)