February 2007

2-in-1 approach to prolapse surgery prevents incontinence

Issue 09: 24 Apr 2006
Source: New England Journal of Medicine 2006; 354: 1557-66
The incidence of stress urinary incontinence following surgery for pelvic organ prolapse in women can almost be halved by performing Burch colposuspension at the same time as abdominal sacrocolpopexy, according to new findings.
Researchers from centers across the USA recruited 322 women who were due to undergo sacrocolpopexy to treat prolapse and who did not report already having symptoms of stress incontinence.
Of these women, 157 were randomly assigned to undergo concomitant Burch colposuspension, and 165 were allocated to the control group of no Burch colposuspension.
Three months after surgery, at blinded evaluations, 23.8 percent of the sacrocolpopexy plus Burch colposuspension group and 44.1 percent of the controls were found to meet one of more of the criteria for stress incontinence, according to the Pelvic Floor Distress Inventory (PFDI) questionnaire and the results of stress testing. This was a statistically significant difference.
In addition, women in the combined surgery group were significantly less likely than women in the control group to report “bothersome” symptoms of stress incontinence, based on responses to the PFDI questionnaire (6.1 percent versus 24.5 percent, respectively).
There was no significant difference between the two groups in rates of urge incontinence (32.7 percent in the combined surgery group and 38.4 percent in the control group).
"An important advance"
The researchers, writing in the New England Journal of Medicine, conclude: “In women without stress incontinence who are undergoing abdominal sacrocolpopexy for prolapse, Burch colposuspension significantly reduced postoperative symptoms of stress incontinence without increasing other lower urinary tract symptoms.”
They say further work is needed to determine whether the benefits of the combined surgery approach persist beyond 3 months, and whether they apply to other prolapse and continence procedures.
Dr Duane Alexander, the director of the USA’s National Institute of Child Health and Human Development, which helped fund the study, said: “This is an important advance in treatment for a large number of women. More than 200,000 women have prolapse surgery every year [in the USA], and these research findings could prevent incontinence in many of them.”

Prenatal diagnosis miscarriage risk overestimated

Source: Obstetrics & Gynecology 2006; Not yet available online
Assessing how miscarriage rates after chorionic villus sampling and amniocentesis changed between 1983 and 2003.
The risk of miscarriage after prenatal diagnostic tests is lower than previously thought, and may be no higher after chorionic villus sampling (CVS) than amniocentesis, research suggests.
The results are based on data for 9886 CVS procedures and 30,983 amniocentesis procedures performed at The University of California at San Diego Medical Center between 1983 and 2003.
Testing with CVS, which can be performed earlier in gestation than amniocentesis, has typically been thought to bring a higher risk of miscarriage.
This trend was maintained, overall, in the current study, which showed that the rate of pregnancy loss for women undergoing CVS (3.12 percent) was higher than that for those undergoing amniocentesis (0.83 percent), report the researchers led by Aaron Caughey (University of California at San Francisco, USA).
However, when the data were examined at 5-year intervals, loss rates for both procedures fell over time and the difference between the two procedures decreased.
After controlling for gestational age and maternal age, losses from CVS and amniocentesis were equivalent.
"If there is no difference in risk associated with CVS and amniocentesis, women are more likely to choose CVS because information can be provided much sooner," said study co-author Mary Norton.
Norton notes that a possible reason for the reduction in miscarriage after CVS is that practitioners have improved. Given this and the fact the results were obtained from a single center, the researchers warn that the findings may not be applicable to all institutions.

Prevention of preterm births

Issue 16: 31 Jul 2006
Source: US Institute of Medicine report Preterm Birth: Causes, Consequences, and Prevention
A multidisciplinary research effort is needed in order to provide a better understanding of preterm births and how to prevent them, a new report has concluded.
The report, Preterm Birth: Causes, Consequences, and Prevention, was produced by a committee of specialists convened by the US Institute of Medicine, and a summary is available from the website http://www.iom.edu/.
The report is in part a response to a steadily rising incidence of preterm births, which are defined as births occurring before 37 weeks’ gestation. In the USA, the proportion of live births that are preterm has risen from 10.6 percent in 1990 to 12.5 percent in 2004.
The highest rates are among African-American women (17.8 percent in 2003), and the lowest rates are among Asian or Pacific Islander women (10.5 percent and 11.5 percent respectively in 2003). According to the new report, differences in socioeconomic conditions and maternal behaviors cannot fully account for these differences.
A research agenda
The report includes a proposed agenda for future research. It says a multidisciplinary approach will be needed, to take into account the inter-related biological, psychological, social and environmental factors involved in preterm birth. Multidisciplinary research centers should be established by public and private research centers, the report suggests.
It recommends that researchers focus on:
“Better defining the problem of preterm birth, including the use of ultrasound in the first trimester to accurately establish gestational age.”
“Conduct[ing] studies to improve the clinical treatment of women who deliver preterm and infants born preterm, and the health care systems that care for them.”
“Examin[ing] the multiple causes of preterm birth, including investigating reasons for disparities among different racial, ethnic, and socioeconomic groups.”
“Conducting studies that will help increase our understanding of the impact of preterm birth on various public programs and policies, and how policies can be used to reduce the rates of preterm birth.”
Progress in the understanding and prevention of preterm births “requires acknowledgement that it is not one disease with a single solution or cure, but rather the product of overlapping factors,” the report states.
Dr Richard Behrman, chairman of the Institute of Medicine committee that produced the report (the Committee on Understanding Premature Birth and Assuring Healthy Outcomes) said: “Despite great strides in improving the survival of infants born preterm, little is known about how preterm births can be prevented. Any significant gains to be made in the study of preterm birth will be made in the area of prevention.”
It also recommends that further efforts are made to reduce the number of multiple births (a risk factor for preterm birth) that results from infertility treatment.

Pregnancy in older women

Issue 12: 6 Jun 2006
Source: European Journal of Obstetrics & Gynecology and Reproductive Biology 2006; 126: 33-8
“Advanced maternal age of 40 years and over was not associated with adverse maternal and perinatal outcome, although the incidence of cesarean section was significantly increased in these women,” specialists have concluded after conducting a retrospective review of records.
The researchers from centers in Safat, Kuwait, reviewed data on all 168 women aged 40 years or over (mean age 41.5 years) who delivered singleton pregnancies at the Safat Maternity Hospital during a 30-month period. A control group consisted of 160 women aged 25-30 years.
Writing in the latest issue of the European Journal of Obstetrics & Gynecology and Reproductive Biology, the researchers report that the older women has a significantly higher mean parity, of 4.24 compared with 1.69 in the control group.
A past history of cesarean section was also significantly more prevalent among the older women (24.4 percent) than among the control group (11.9 percent).
Most of the pregnancies in each group were spontaneous. Among the older women, 4 percent of the pregnancies were initiated by assisted reproductive technology.
Older vs younger women
The researchers observed a significantly higher overall incidence of antenatal complications in the study group (57.1 percent) than in the control group (12.5 percent). Complications that were significantly more common in the study group were diabetes mellitus, essential hypertension, pregnancy-induced hypertension, and premature rupture of membranes. These contributed to a significantly higher rate of induction of labor in the study group (24.4 percent compared with 11.9 percent among controls).
Significantly more women in the study group underwent a cesarean section: 31 percent compared with 16.3 percent of the control group. In addition, the mean gestational age at delivery was significantly lower among the older women: 38.06 weeks compared with 39.31 weeks in the control group.
The mean birth weights were similar in each group, although the proportion of infants who were 2500 g or less was significantly higher among the older women (10.7 percent of births) than the control group of younger women (3.8 percent of births).
The researchers report that the overall perinatal outcomes of the study and control groups were “comparable and quite satisfactory.” They also say that no significant adverse intrapartum or postpartum maternal morbidity was observed, and no maternal mortality was reported.
Discussing their findings, the researchers say several factors help explain the satisfactory overall maternal and perinatal outcome in the women aged 40 or over. These include “the fact that we have well-equipped medical facilities, high-quality obstetric personnel and a policy of early intervention, low incidence of antenatal, intrapartum and postpartum complications in the study population, and generally a healthy patient population who tend to be of higher socio-economic status.”
On a related subject, see the article Maternal age and stillbirths, from the ORGYN Online Magazine issue of 27 March 2006. This discusses research showing that women at the extremes of maternal reproductive age (younger than 20 years or older than 34 years) were more likely than women of intermediate age to have a stillbirth.

Understanding PCOS

Issue 15: 17 Jul 2006
Source: Best Practice & Research Clinical Endocrinology & Metabolism 2006; 20: 193-205
A new review paper has addressed the current state of knowledge of the diagnosis, epidemiology, and genetics of polycystic ovary syndrome (PCOS).
In the latest issue of the journal Best Practice & Research Clinical Endocrinology & Metabolism, specialists from centers in Los Angeles, USA, provide a detailed review of published evidence. In particular, they note the controversy that exists in defining, and therefore diagnosing, PCOS.
Their findings are summarized at the end of the paper in a list of four “practice points”. These state:
“PCOS is a diagnosis of exclusion, such that other androgen excess or ovulatory disorders with clearly defined etiologies are to be excluded.”
“To date, two major diagnostic criteria have been proposed.” The NIH 1990 criteria define PCOS as biochemical and/or clinical hyperandrogenism and ovulatory dysfunction, after excluding related or other disorders. The Rotterdam 2003 criteria define PCOS as present if two of the following three criteria are met, after excluding related or other disorders: biochemical and/or clinical hyperandrogenism, ovulatory dysfunction, and polycystic ovaries.
“Whether the two new phenotypes proposed by the Rotterdam 2003 criteria [women with polycystic ovaries and ovulatory dysfunction but no hyperandrogenism, and women with polycystic ovaries and hyperandrogenism but no ovulatory dysfunction] actually represent PCOS and/or have similar long-term morbidities remains to be determined, and a delay in the adoption of these criteria is recommended.”
“Consequently, the prevalence of clinically evidence PCOS in unselected women of reproductive age, using the 1990 NIH criteria, ranges from 6.5 to 8.0%; it may be higher if more expansive diagnostic criteria are used.”
The authors also suggest a research agenda to address unanswered questions about PCOS. This includes a call for cross-sectional and longitudinal studies to investigate the two new phenotypes proposed by the Rotterdam 2003 criteria, plus studies of ethnic differences in the prevalence of PCOS, and of molecular and genetic factors involved in PCOS.

Preventing further miscarriages

Issue 17: 14 Aug 2006
Source: Fertility and Sterility 2006; 86: 362-6
Women with unexplained recurrent miscarriages and without thrombophilia could benefit from thromboprophylaxis in future pregnancies, new research suggests.
Researchers from centers in Israel performed a prospective randomized study of the effect of thromboprophylaxis, with enoxaparin or aspirin, on pregnancy outcomes in 104 women with previous unexplained consecutive recurrent miscarriages (three or more in the first trimester, or at least two second-trimester fetal losses).
Women with thrombophilia, anatomical abnormalities, or intrauterine adhesions, were among those excluded from the study.
The women were randomized to take 40 mg enoxaparin (54 women) or 100 mg aspirin daily (50 women) from the time of detection of a fetal heart beat, at 6-12 weeks’ gestation, until the end of the pregnancy.
Births and complications
Reporting their findings in the journal Fertility and Sterility, the researchers say there was no significant difference between groups in the live birth rate: 81.5 percent (44/54 women) in the enoxaparin group and 84 percent (42/50 women) in the aspirin group.
Among the subgroup of women the researchers called primary aborters (all previous pregnancies has terminated as miscarriages), live births occurred in 17 of the 18 (94 percent) in the enoxaparin group, and 18 of the 22 (81 percent) in the aspirin group.
Preterm delivery rates, placental Doppler blood flow, Apgar scores, and mean birthweights were similar in both groups.
Discussing their findings, the researchers note some limitations of their study, including the lack of a placebo control group. They add that the reason for including enoxaparin in the study was because, like aspirin, it has anti-inflammatory effects as well as anticoagulant effects.
Concluding, the researchers write: “Both regimens were associated with a high live-birth rate and few late-pregnancy complications.” They add: “In view of the minimal risks of enoxaparin and aspirin to the mother and fetus, either form of treatment should be considered in women after three or more pregnancy losses.”
In 2003, the UK’s Royal College of Obstetricians and Gynaecologists (RCOG) issued evidence-based recommendations for managing couples with recurrent miscarriage. For an overview of the advice, see the ORGYN Online Magazine article Tackling recurrent miscarriage

March 2007

Obesity and infertility

Issue 15: 17 Jul 2006
Source: Maturitas 2006; 54: 363-71
The negative effects of obesity on fertility, in women and in men, are examined in detail in a new review paper.
The author, Professor Renato Pasquali from the Endocrinology Unit at the University of Bologna, Italy, concludes that these adverse effects “appear to be mainly related to disorders of sex hormone secretion and/or metabolism, leading in turn to a condition of relative hyperandrogenism in obese women and of hypotestosteronemia (and, in some cases, a true hypogonadotropic hypogonadism) in obese men.”
The author discusses reproductive disorders in obese women under a series of headings: epidemiological aspects and age-related factors; obesity and polycystic ovary syndrome (PCOS); drug-induced ovulation, miscarriages and pregnancy rates; assisted reproductive technology and obesity; and mechanistic factors of infertility in obesity.
The adverse effects of obesity on fertility on obese women are summarized as:
Precocious menarche.
Menstrual alterations (oligo-amenorrhea).
Chronic oligo- or anovulation.
Relative hyperandrogenic state.
Pathophysiological implication in polycystic ovary syndrome (PCOS).
Increased risk of [spontaneous] abortion.
Reduced rates of pregnancy after assisted reproductive technology.
Increased risk of morbidity in obese pregnant women.
Preterm deliveries and increased fetal morbidity and mortality.
The author notes that the impact of obesity on fertility has not been investigated as much in men as it has in women. Clinical data, however, “support the concept that fertility problems are not uncommon in the presence of obesity, particularly grade 3”, in men, he writes.
The potential negative effects of obesity on fertility in men are summarized as: hypotestosteronemia; hypogonadotropic hypogonadism (in massive obesity); erectile dysfunction; and reduced spermatogenesis (although this is rare).
The author also notes that published research has shown that weight loss can improve hormonal abnormalities and fertility rates in both women and men.
The full review paper is published in the latest issue of the journal Maturitas. To read other ORGYN Online Magazine articles related to this topic, see Advice on obesity and pregnancy (from the 19 September 2005 issue) and BMI and pregnancy outcomes (from the 16 June 2003 issue).

Menstrual cycle length before the menopause

Issue 18: 28 Aug 2006
Source: Fertility and Sterility 2006; in press (currently available at http://www.sciencedirect.com/)
In a new paper researchers have challenged landmark findings on the lengths of perimenopausal menstrual cycles.
A 1967 paper by Treloar et al, published in the International Journal of Fertility, estimated that between the age of 20 years and early perimenopause, the mean length of menstrual cycles fell from 30 to just under 27 days.
In the 4 years immediately before menopause, the mean cycle length increased to 57 days. These findings are cited widely in medical textbooks and in studies of reproductive aging.
But in a new paper to be published in the journal Fertility and Sterility, researchers from centers in Washington, Princeton and Seattle, USA, describe how these estimates were distorted by bias. They then present their own analysis, excluding these biases, of the prospectively collected menstrual cycle data that were used in the 1967 paper.
They report large differences between the original analysis and new analysis in the estimated mean menstrual cycle length for each of the 4 years before menopause:
4th year before menopause: mean menstrual cycle length is 33.60 days in the original analysis, 30.48 days in the new analysis.
3rd year before menopause: 43.91 days in the original analysis, 35.02 days in the new analysis.
2nd year before menopause: 55.87 days in the original analysis, 45.15 days in the new analysis.
1st year before menopause: 54.58 days in the original analysis, 80.22 days in the new analysis.
In the year before menopause, more than half of the women were spending at least 75 percent of that year in menstrual cycles of more than 40 days.
The researchers write that, in their reanalysis, “the increase in mean cycle length as a woman approached menopause began to occur closer to menopause than previously thought, but the extent to which a woman’s cycles lengthened as she approached menopause was actually greater than previously thought.”
In the paper they discuss in depth the implications of the new findings for clinical practice and for research.
This discussion includes the suggestion of monitoring time spent in cycles of more than 40 days: “The percentage of a year that a woman spends in >40-day cycles is a multiple-event measure that women could record and share with their physicians.” This could be useful in informing management decisions, they state. “It may be consequential in determining the time until onset of menopause, often a critical determinant in choosing between hormonal therapy and surgical (hysterectomy) options for a patient with perimenopausal menorrhagia.”

Predicting the timing of menopause (part 2)

 
Issue 09: 24 Apr 2006
Source: European Journal of Obstetrics & Gynecology and Reproductive Biology 2006; 125: 221-5
A newly published study has added to current knowledge of the factors that may affect the timing of natural menopause.
Publication of the new study, in the latest issue of the European Journal of Obstetrics & Gynecology and Reproductive Biology, follows another recent paper on the same subject.
Earlier this year, researchers in Vienna, Austria, reported their development and testing of a formula for predicting age at natural menopause, based on personal medical history and the findings of genetic tests. The formula used five variables:
The number of full-term pregnancies.
The presence of at least one mutant allele of the gene CYP17.
A personal history of breast surgery.
The presence of at least one mutant allele of the gene CYP1B1-4.
Body mass index.
For more on this, see the article Predicting the timing of menopause, from the ORGYN Online Magazine issue dated 13 February 2006.
The new study, involving some of the same researchers from Vienna, investigated the effect of lifestyle parameters, personal history, and a common polymorphism called SRD5A2 (involved in androgen metabolism) on the timing of natural menopause in 323 postmenopausal Caucasian women.
Of these women, about half carried the mutant allele (either homozygously or heterozygously).
Only one significant association
After analysing the data collected from the 353 women, the researchers found that the only factor significantly associated with the timing of menopause was the number of full-term pregnancies: the more full-term pregnancies, the later the natural menopause. The average age at natural menopause was 48.3 years in women with no full-term pregnancies, and 49.6 years in women with a history of two or more.
The researchers suggest that, because ovulation is suppressed during and shortly after pregnancy, oocyte depletion is delayed in parous women, pushing the timing of menopause to a later date.
Other factors studied, including the presence of the SRD5A2 polymorphism, smoking, body mass index, and a history of breast cancer, were not found to have any association with age at natural menopause. The researchers comment that the apparent lack of effect of the SRD5A2 polymorphism was “surprising”, but add that its possible associations with menopause timing needs to be studied in other populations also

Women prefer examinations without stirrups

 
Issue 16: 31 Jul 2006
Source: British Medical Journal 2006; 333: 171-3 & 173-4
Women undergoing a speculum examination feel less vulnerable and more comfortable when stirrups are not used, according to new study findings.
Researchers from centers in Augusta and Fort Gordon, in Georgia, USA, randomized 197 women undergoing speculum examination as part of a routine gynecological examination into two groups: “stirrup” and “non-stirrup”.
Women in the stirrup group were examined with their heels placed in uncovered metal stirrups at 30-45 degree angles to the examination table. In the non-stirrup group, women were examined with their feet placed on the corners of a fully deployed table extension.
Afterwards, the women completed questionnaires about their perceived level of physical discomfort, their sense of vulnerability, and their sense of control during the examination. Visual analogue scales were used in order to provide quantitative measures.
Reporting their findings in the British Medical Journal, the researchers say the women in the non-stirrup group felt significantly less vulnerable and more comfortable than women in the stirrup group. The mean sense of vulnerability was 23.6 in the stirrup group, but only 13.1 in the non-stirrup group (a reduction of 44 percent). The mean level of physical discomfort was 30.4 in the stirrup group, but only 17.2 in the non-stirrup group (a reduction of 43 percent).
There was no significant difference between groups in terms of the sense of control. In addition, there was no difference between groups in the quality of smears.
The researchers conclude: “Women should be able to have gynaecological examinations without using stirrups, to reduce the stress associated with speculum examinations.”
Commentary and recommendations
In a commentary article on the paper, UK-based authors suggest that the study’s findings should change practice in the USA. They note that, in the UK, most speculum examinations for routine cervical smears are performed in general practice or family planning clinics, and stirrups tend not to be used.
They also refer to guidelines on conducting vaginal examinations, published by the UK’s Royal College of Obstetricians and Gynaecologists in 2002. These include:
“Explain the reason for doing a vaginal examination and obtain verbal consent.”
“Offer to find a chaperone and record this in the notes.”
“Provide privacy to undress and use drapes to maintain the patient’s dignity.”
“Use a closed room and avoid interruptions during the examination.”
“During the examination: be gentle, explain what you are doing, be alert to indications of distress, avoid personal comments.”

Scale evaluates self-efficacy in infertility

 
Issue 13: 19 Jun 2006
Source: Fertility and Sterility 2006; 85: 1684-96
Researchers have reported the development and validation of a rating scale to assess self-efficacy among infertile patients. The Infertility Self-Efficacy (ISE) scale “appears to be a reliable and valid measure of an individual’s self-confidence in areas related to health promotion during infertility treatment,” they conclude.
Writing in the journal Fertility and Sterility, the researchers from centers in Connecticut and Massachusetts, USA, note that other measures of mental health used in infertility tend to be either distress-focused (such as the Beck Depression Inventory) or problem-focused (such as the Ways of Coping questionnaire, Fertility Problem Inventory, and Infertility Questionnaire).
In contrast, the ISE scale focuses on a person’s perceived ability and confidence to engage in particular health promoting activities or behaviors. The researchers provide an example, noting that an infertile woman may have high self-efficacy initially, and perceive herself to have the confidence and skills needed to perform treatment tasks such as self-injection. However, after multiple pregnancy losses or failed treatment cycles, her perceived self-efficacy may be poorer, at which point psychological intervention could be helpful.
In the new paper, the researchers report in detail how they developed, tested, refined and validated the ISE scale. This process involved the recruitment of 213 people (159 women and 54 men) diagnosed with infertility in the past 2 years.
The final, validated ISE consists of 16 items, including the following:
“Ignore or push away unpleasant thoughts that can upset me during medical procedures”
“Keep a sense of humor”
“Make meaning out of my infertility experience”
“Handle mood swings caused by hormonal treatments”
“Keep from being discouraged when nothing I do seems to make a difference”
“Accept that my best efforts may not change my/our infertility”
“Control negative feelings about infertility”
“Cope with pregnant friends and family members”.
The researchers note that there were sex differences, in that men tended to have significantly higher self-efficacy scores on the ISE, compared with women. However, they note that the study sample was biased towards women, and that further work is needed on use of the ISE in men.
After an extensive discussion of their overall findings, they conclude: “Assessing an infertility patient’s self-efficacy with the ISE may be useful in clinical research and as a counseling tool to help guide patients in actively managing their fertility treatment.”

Promoting the obstetrics evidence base

Issue 17: 14 Aug 2006
Source: International Journal of Gynecology & Obstetrics 2006; 94: 179-84
Obstetric interventions and devices that have the support of a good evidence base but are not universally applied are the subject of a new paper.
The authors, from the United Nations Population Fund (UNFPA) in Geneva, Switzerland, and Addis-Ababa, Ethiopia, say the limited use of certain evidence-based obstetric practices is a major obstacle to the improvement of care.
In their paper in the International Journal of Gynecology & Obstetrics, they list the key evidence-based interventions, with supporting references. They note that the list is not exhaustive and “is limited to obstetric interventions during the very end of pregnancy, labor, and the immediate post-partum period, that can be performed for the most part by a skilled attendant.”
The list, presented under several main headings, includes the following (each intervention is discussed in more detail in the full paper):
Preventing and managing postpartum hemorrhage: active management of the third stage of labor, use of oxytocin, use of pre-filled syringes.
Controlling hypertensive disorders of pregnancy: use of magnesium sulfate.
Addressing prolonged/obstructed labor: use of WHO partograph, vacuum extraction, cesarean section under regional anesthesia with antibiotic prophylaxis, symphysiotomy, external cephalic version after 37 weeks of gestation.
Controlling infection: antibiotic prophylaxis, antibiotic treatment, prevention of mother-to-child transmission of HIV, syphilis screening and treatment.
Integrating newborn care: routine induction of labor after 41 weeks, care of the newborn with asphyxia, skin-to-skin method (kangaroo method).
For each of these categories, the authors also discuss promising interventions, practices and devices that have not yet been subjected to multicenter trials or Cochrane reviews.
In their discussion, the authors say wider utilization of the evidence-based interventions may require the revision of national guidelines and regulations. They add that the providers of such interventions should also be given protections against liability.
For more information on evidence-based obstetrics, the authors suggest readers visit the WHO Reproductive Health Library at http://www.rhlibrary.com/. An online or CD-ROM subscription is free to visitors in countries on the UN list of less-developed countries

Embryo transfer: day 2 or day 3?

Issue 18: 28 Aug 2006
Source: Fertility and Sterility 2006; 86: 44-50
Embryo transfer on day 2, rather than day 3, leads to improved clinical outcomes in women under 40 who have a low number of embryos to transfer, the results of a new study suggest.
Delaying embryo transfer to day 3 (in order to optimize embryo selection by observing the initial transition to embryonic gene expression control) is well accepted. But specialists at the University of California, in San Francisco, USA, wanted to determine whether culturing embryos for 1 day less was of any benefit in the subgroup of IVF patients who do not have a sufficient number of embryos available for selection (and in whom all embryos will usually be transferred, irrespective of quality).
In a paper in the journal Fertility and Sterility, they present their study of 242 fresh IVF/ICSI cycles where all generated embryos were transferred because of their extremely low number.
The original decisions to transfer all embryos were based on patient prognosis (taking into account age, FSH, and prior failed attempts) and the number of embryos available, according to defined criteria (described in detail in the full paper).
The researchers divided the patients into two groups according to age: under 40 years of age, and 40 or over.
In the patients under 40, embryo transfer was performed on day 2 in 65 cycles, and day 3 in 70 cycles. In patients aged 40 or over, embryo transfer was performed on day 2 in 53 cycles, and day 3 in 54 cycles.
In the women under 40, day 2 embryo transfer was associated with significantly improved outcomes compared with day 3 transfer.
More ongoing pregnancies:
After adjusting for confounding factors, women under 40 who had embryo transfer on day 2 were 2.28 times as likely (95 percent confidence interval 1.03-5.04) than those who had embryo transfer on day 3 to have an ongoing pregnancy (defined as those that progressed beyond the first trimester with cardiac activity, or that delivered).
In the day 2 group, there were 30 ongoing pregnancies from 65 cycles. This compared with 20 ongoing pregnancies from 70 cycles in the day 3 group.
Fewer miscarriages:
In addition, women under 40 who had embryo transfer on day 2 were 0.04 times as likely (95 percent confidence interval 0.00-0.54) than those who had embryo transfer on day 3 to have a spontaneous miscarriage. In other words, the odds of a day 2 embryo transfer ending in miscarriage were only 4 percent of those when transferred on day 3.
In the day 2 group, there were two miscarriages from 65 cycles. In the day 3 group, there were nine miscarriages from 70 cycles.
In the group of older women, aged 40 or over, the day of embryo transfer had no significant effect on outcomes.
No advantage to additional day
At the end of their paper, the researchers write: “In conclusion, in cases where there are low numbers of embryos available for transfer, a day 2 ET [embryo transfer] may achieve better clinical outcomes in younger patients (<40 years old), as demonstrated by a significant reduction in miscarriages and improved ongoing pregnancy rates.
“Therefore, there appears to be no advantage to culturing an additional day in this subgroup of patients.”
The researchers add that the results of their study need to be confirmed in further randomized studies.

April  2007

Study assesses short-term diet before IVF

Issue 16: 31 Jul 2006
Source: Fertility and Sterility 2006; 86: 227-9
A short-term effort by overweight or obese women to lose weight before IVF treatment, by adopting a very low calorie diet (VLCD), has no apparent benefit, the results of a pilot study suggest.
Specialists from the University of Adelaide, Australia, conducted a small study to investigate the effects on IVF outcomes of overweight/obese women adopting a VLCD for a short period before and during treatment.
Almost one in three women attending IVF clinics in Australia is overweight or obese.
The researchers recruited 10 overweight or obese women (a body mass index of 28 kg/m2 or more) who had tried to conceive in the previous 3-5 years by having fertility treatments. Four of the women dropped out during the study. The remaining six completed 27-41 days of dietary intervention with a commercially available VLCD: two women began on day 14 of the menstrual cycle, consuming two VLCD sachets plus one regular meal per day, and four women began on day 21, consuming three VLCD sachets per day (the daily recommended amount). One sachet of the VLCD was equivalent to 152 kcal.
Dietary intervention was stopped on the evening before oocyte pick-up.
The six patients achieved a weight loss of 5.3-8.2 kg (mean 5.6 kg), losing from 2.2-8.8 percent of body weight, while on the VLCD. Waist circumference and body mass index were also reduced, compared with baseline figures.
The researchers say the small sample size makes assessment of the effect on IVF outcomes difficult. But they note that, of the six patients, the three who remained on VLCD for more than 4 weeks did have oocytes collected, fertilized and transferred independent of weight loss. The three who had up to 4 weeks of VLCD had no fertilization. This may be a coincidence, the researchers note.
Select diets “cautiously”
They write: “In conclusion, the current study found that using a VLCD for a short time along with IVF treatment is feasible for some patients but not for all. During a 4- to 6-week period, patients had a significant weight loss ranging from 2.2-8.8 percent of their initial weight and, consequently, the reduction of waist circumference or abdominal fat pad.”
They say of the study’s attempts to shed light on the impact of short-term energy restriction on IVF outcomes: “no clear outcome has been reached.”
The researchers conclude that “the lack of apparent benefit suggests that the dietary regime or duration of the diet should be selected cautiously before treatment in overweight and obese women. Because this pilot study demonstrated an unpromising result, acute VLCD is not presently recommended.”
They suggest that longer-term energy restriction could be a better option for such patients, allowing more gradual metabolic and endocrine adaptation.

Adolescents with dysmenorrhea

 
Issue 16: 31 Jul 2006
Source:
Journal of Paediatric and Adolescent Gynecology 2006; 19: 285-9
A new study has yielded insights into moderate to severe dysmenorrhea in adolescent girls, providing information on the associated morbidity and how it is treated.
Researchers from Columbia University Medical Center, in New York, USA, identified and interviewed 76 healthy adolescents with moderate to severe primary dysmenorrhea, as part of the enrollment process for a trial of oral contraceptives. Girls already taking hormonal contraception were excluded.
The girls were aged 19 years or younger, and had a mean age of 16.8 years.
The researchers’ main findings, reported in the latest issue of the Journal of Paediatric and Adolescent Gynecology, include:
Dysmenorrhea was moderate in 42 percent, severe in 58 percent.
55 percent reported associated nausea, 24 percent reported associated vomiting.
Of the 66 subjects attending school, 46 percent said they missed at least 1 day a month due to dysmenorrhea.
The subjects reported a median of 2 days of severe pain during each menses; 12 percent reported 4 or more days of severe pain.
Nearly all of the girls talked about the pain of dysmenorrhea with someone, including their mother (84 percent), friend (67 percent), doctor (37 percent) or nurse (22 percent).
All reported use of at least one non-pharmacological intervention. These were (most popular first): staying in bed or sleeping, taking a hot bath, using a heating pad, watching television or some other distraction, taking a special food or drink, and taking exercise.
93 percent used at least one medication to treat dysmenorrhea. 91 percent used over-the-counter (OTC) medications, including ibuprofen, acetaminophen (paracetamol), and naproxen. 21 percent used prescription medicines, including ibuprofen and naproxen. Most of the girls in the study were using “considerably less than the recommended dose of medication for dysmenorrhea or pain,” the researchers found.
Implications for education
The researchers conclude: “This study indicates that greater education is needed for adolescents with dysmenorrhea, and their parents. There is a demonstrated need by adolescents for information regarding not only effective medications, emphasizing NSAID use, but also appropriate dosing, including prophylactic administration and dosing frequency.”
They add that further research should address the extent to which healthcare professionals caring for adolescent girls offer appropriate treatment, including prescription doses of effective medication.

Low-risk cesareans carry increased neonatal mortality risk

Source: Birth 2006; Not yet available online
Examining infant and neonatal mortality among women with no indication of medical risks or complications who undergo a primary cesarean delivery.
Low-risk mothers who opt for a cesarean face a higher risk of infant and neonatal mortality than those who deliver vaginally, researchers report.
"These findings should be of concern for clinicians and policy makers who are observing the rapid growth in the number of primary cesareans to mothers without a medical indication," said Marian McDorman, who led the study.
The team, from the Centers for Disease Control and Prevention in Atlanta, Georgia, analyzed data on more than 5.7 million live births and 12,000 infant deaths over a 4-year period. The researchers focused on women with a singleton full-term gestation and no indicated medical risks or complications.
They found that, overall, infants born to these low-risk women had a low incidence of neonatal death, at about one in 1000 live births. However, further analysis showed that those delivered by cesarean section had twice the risk of death as those delivered vaginally.
This is worrying because the overall rate of cesarean delivery rose by 41 percent between 1996 and 2004 in the USA, while the incidence in women with no indication for cesarean almost doubled.

Diabetes and pregnancy outcomes

Issue 14: 3 Jul 2006)
Source: British Medical Journal 2006 (available online, doi: 10.1136/bmj.38856.692986.AE, published 16 June 2006)
Perinatal mortality and the prevalence of congenital anomalies are higher than average in the babies of women with type 1 or type 2 diabetes, compared with the general maternity population, according to new study findings.
Researchers from the UK’s Confidential Enquiry in to Maternal and Child Health analyzed data from 231 maternity units in England, Wales, and Northern Ireland, in one of the largest studies of pregnancy outcomes in women with diabetes.
The data covered 2,359 pregnancies to women with type 1 or type 2 diabetes who delivered in a 1-year period beginning on 1 March 2002. Of the 2,359 pregnancies, 1,707 of the women had type 1 diabetes and 652 had type 2 diabetes.
The women with type 2 diabetes were more likely than those with type 1 diabetes to come from a black, Asian or other ethnic minority group, and from a deprived area.
Perinatal mortality
Perinatal mortality was similar in both groups: 31.7 per 1,000 total births for women with type 1 diabetes, and 32.3 per 1,000 total births for women with type 2 diabetes. The overall rate was 31.8 per 1,000, almost four times higher than that of the general maternity population according to national data from 2002.
Congenital anomalies
A total of 141 major congenital anomalies occurred in 109 offspring of the women with diabetes, resulting in an overall prevalence of 46 per 1,000 total births (48 per 1,000 for women with type 1 diabetes, and 43 per 1,000 for women with type 2 diabetes). This is more than twice the rate of major anomalies observed in the general maternity population.
Contributing to the higher rate of anomalies were high rates of neural tube defects (4.2 times the general rate) and congenital heart disease (3.4 times the general rate).
Both are high-risk groups
Noting that most previous research on this subject had focused on women with type 1 diabetes, the researchers conclude that perinatal mortality and the prevalence of congenital anomalies “do not seem to differ between the two types of diabetes.”
Women with either type should be considered a high-risk group during pregnancy, the researchers suggest. They add: “As the incidence of diagnosed diabetes continues to increase, especially at young ages, the number of women with diabetes in pregnancy will also continue to increase.”

Chromosomal abnormalities and reproductive failure

 
Issue 15: 17 Jul 2006
Source: European Journal of Obstetrics & Gynecology and Reproductive Biology 2006; 127: 106-9
A study has identified major chromosomal abnormalities in about 1 in 20 couples experiencing repeated spontaneous abortions in recognized pregnancies. Minor abnormalities were found in about 1 in 6 couples.
Specialists at Karadeniz Technical University in Trabzon, Turkey, studied cytogenetic data from 645 couples (1290 patients) treated at the center who had experienced repeated spontaneous abortion. This was defined as either having had at least two first-trimester spontaneous abortions or having had one first-trimester spontaneous abortion and a second- or third-trimester fetal death and/or malformed child.
The researchers present their results in a new paper in the European Journal of Obstetrics & Gynecology and Reproductive Biology. They identified major chromosomal abnormalities in 25 couples (3.86 percent). Abnormalities classified as major included reciprocal and robertsonian translocations, inversions, deletions, sex chromosome aneuploidies, and mosaicism of either numerical or structural abnormalities.
Most of the major abnormalities identified were structural (3.71 percent), and only a few were numerical (0.15 percent).
In addition, the researchers identified relevant polymorphisms in 115 couples (17.51 percent).
Investigation “important and necessary”
Discussing their findings, the researchers say the prevalence of major chromosomal abnormalities seen in the study (3.86 percent) is in agreement with published literature (various rates up to 13.1 percent).
They discuss in detail the implications of the identified abnormalities, and say the data “confirm that chromosomal studies in couples with reproductive failure are an important and necessary part of the etiological investigations.” Chromosomal studies should be performed in all couples with reproductive failure and/or fetal death, the researchers write.
They emphasize that the results also provide further evidence that there are non-cytogenetic factors associated with recurrent miscarriage.

The ABC of laparoscopic entry

 
Issue 14: 3 Jul 2006
Source: Journal of Minimally Invasive Gynecology 2006; 13: 249-51
A three-step “ABC” of laparoscopic entry that minimizes complications is described in a new paper.
Past research has shown that at least 50 percent of laparoscopic complications occur during the initial entry into the abdomen, regardless of the method used.
In the latest issue of the Journal of Minimally Invasive Gynecology, Dr George Vilos from the department of obstetrics and gynecology at the University of Western Ontario, in London, Canada, shares the techniques he uses to prevent complications during closed entry (the type of entry used by most gynecologists worldwide, according to published research).
Three steps
The ABC of laparoscopic entry put forward by the author is as follows:
A = Low initial Veres intraperitoneal pressure (LIVIP-pressure).
B = High-pressure pneumoperitoneum entry (HIP-pneumo entry).
C = Visual entry with the Ternamian cannula.
Each of these is described in detail in the full paper.
The author reports that he has been practicing LIVIP-pressure and HIP-pneumo entry since 1997, and adopted visual entry with the Ternamian cannula in 2000.
Before 1997, he writes, he experienced 10 injuries during laparoscopic access in 3,472 consecutive laparoscopies. These were three small-bowel punctures with the Veres needle, three small-bowel injuries with the primary trocar, two large-bowel injuries with the primary trocar, and two primary-trocar injuries to large bowel and major vessels.
Since 1997 there have been three complications in more than 3,000 consecutive laparoscopies: two large-bowel Veres needle punctures, requiring no treatment, and one transverse colon puncture with the primary trocar. No vascular injuries have occurred.

May  2007

June  2007

Early initiation of feeding was associated with reduced time to return of bowel sounds, reduced postoperative hospital stay and with suggestion of reduced abdominal distention. There is no evidence to justify a policy of restricting oral fluids or food after uncomplicated caesarean section

Abstract

The role of prostaglandins for cervical ripening and induction of labour has been examined extensively. Human semen is the biological source that is presumed to contain the highest prostaglandin concentration. The role of sexual intercourse in the initiation of labour is uncertain. The action of sexual intercourse in stimulating labour is unclear, it may in part be due to the physical stimulation of the lower uterine segment, or endogenous release of oxytocin as a result of orgasm or from the direct action of prostaglandins in semen. Furthermore nipple stimulation may be part of the process of initiation.
This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology.

To determine the effects of sexual intercourse for third trimester cervical ripening or induction of labour in comparison with other methods of induction.

The Cochrane Pregnancy and Childbirth Group trials register (March 2004) and bibliographies of relevant papers.

Clinical trials comparing sexual intercourse for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods.

A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction.

There was one included study of 28 women which reported very limited data, from which no meaningful conclusions can be drawn.

The role of sexual intercourse as a method of induction of labour is uncertain. Any future trials investigating sexual intercourse as a method of induction need to be of sufficient power to detect clinically relevant differences in standard outcomes. However, it may prove difficult to standardise sexual intercourse as an intervention to allow meaningful comparisons with other methods of induction of labour.

Abstract

Antenatal maternal glucose administration has been suggested to improve the efficiency of antepartum fetal heart rate testing.

The objective of this review was to assess the merits or adverse effects of antenatal maternal glucose administration in conjunction with tests of fetal wellbeing.

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2006).

All published and unpublished randomized controlled trials assessing the merits of antenatal maternal (oral or intravenous) glucose administration in conjunction with tests of fetal wellbeing.

Both reviewers independently extracted data and assessed trial quality. Authors of published and unpublished trials were contacted for further information.

A total of two trials with a total of 708 participants were included. Antenatal maternal glucose administration did not decrease the incidence of non-reactive antenatal cardiotocography tests.

Antenatal maternal glucose administration has not been shown to reduce non-reactive cardiotocography. More trials are needed to further substantiate this and to determine not only the optimum dose, but also to evaluate the efficacy, predictive reliability, safety and perinatal outcome of glucose administration in conjunction with cardiotocography and also other tests of fetal wellbeing.

Abstract

The use of enemas during labor usually depends on the preference of the attending physician and available resources. However enemas cause discomfort in women and increase the costs of delivery.

The objective of this review was to assess the effects of enemas during the first stage of labor on infection rates in mothers and newborns, duration of labor, perineal wound dehiscence in the mother, perineal pain, faecal soiling and costs.

We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effectiveness, Medline and reference lists of articles.

Randomised trials in which an enema was administered during the first stage of labor and which included assessment of possible neonatal or puerperal morbidity or mortality.

Selected studies were assessed by three reviewers independently.

Two trials involving 665 women were included. These showed no clear difference in infection rates for puerperal mothers (odds ratio 0.61, 95% confidence interval 0.36 to 1.04) or newborn children.

There is not enough evidence to evaluate the use of routine enemas during the first stage of labor.

Abstract

A meta-analysis of observational studies have suggested that planned home birth may be safe and with less interventions than planned hospital birth.

The objective of this review was to assess the effects of planned home birth compared to hospital birth on the rates of interventions, complications and morbidity as determined in randomized trials.

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2006).

Controlled trials comparing planned hospital birth to planned home birth in selected women, assisted by an experienced home birth practitioner, and backed up by a modern hospital system in case transfer should be necessary.

Trial quality was assessed and data were extracted by one review author and checked by the other author. Study authors were contacted for additional information.

One study involving 11 women was included. The trial was of reasonable quality, but was too small to be able to draw conclusions.

There is no strong evidence to favour either planned hospital birth or planned home birth for low-risk pregnant women.

Abstract

Breast stimulation has been suggested as a means of inducing labour. It is a non-medical intervention allowing women greater control over the induction process. This is one of a series of reviews of methods of cervical ripening and labour induction using a standardised methodology.

To determine the effectiveness of breast stimulation for third trimester cervical ripening or induction of labour in comparison with placebo/no intervention or other methods of induction of labour.

The Cochrane Pregnancy and Childbirth Group Trials Register (March 2004) and bibliographies of relevant papers.

Clinical trials of breast stimulation for third trimester cervical ripening or labour induction.

A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction.

Six trials (719 women) were included.
Analysis of trials comparing breast stimulation with no intervention found a significant reduction in the number of women not in labour at 72 hours (62.7% versus 93.6%, relative risk (RR) 0.67, 95% confidence interval (CI) 0.60 to 0.74). This result was not significant in women with an unfavourable cervix. A major reduction in the rate of postpartum haemorrhage was reported (0.7% versus 6%, RR 0.16, 95% CI 0.03 to 0.87). No significant difference was detected in the caesarean section rate (9% versus 10%, RR 0.90, 95% CI 0.38 to 2.12) or rates of meconium staining. There were no instances of uterine hyperstimulation. Three perinatal deaths were reported (1.8% versus 0%, RR 8.17, 95% CI 0.45 to 147.77).
When comparing breast stimulation with oxytocin alone the analysis found no difference in caesarean section rates (28% versus 47%, RR 0.60, 95% CI 0.31 to 1.18). No difference was detected in the number of women not in labour after 72 hours (58.8% versus 25%, RR 2.35, 95% CI 1.00 to 5.54) or rates of meconium staining. There were four perinatal deaths (17.6% versus 5%, RR 3.53, 95% CI 0.40 to 30.88).

Breast stimulation appears beneficial in relation to the number of women not in labour after 72 hours, and reduced postpartum haemorrhage rates. Until safety issues have been fully evaluated it should not be used in high-risk women. Further research is required to evaluate its safety, and should seek data on postpartum haemorrhage rates, number of women not in labour at 72 hours and maternal satisfaction.