Clinical Review

Since the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena, Bayer Health Care Pharmaceuticals) ( FIGURE 1 ) was introduced in the United States in 2001, more than 2 million devices have been used by women here. This use has contributed to a cumulative experience of 14 million women (36 million woman-years of experience) in 120 countries over the last 18 years.

Recent Food and Drug Administration (FDA)-approved labeling changes for the LNG-IUS¹ expand the pool of women who are candidates for this convenient, reversible method of contraception. This article summarizes those labeling changes and answers questions that are often asked by clinicians who, more and more, insert the LNG-IUS for their patients.

FIGURE 1 LNG-IUS, arms open

The LNG-IUS device is readily visible on radiographs. Visualization by ultrasonography is more challenging.

SOURCE: BAYER HEALTH CARE PHARMACEUTICALS. USED WITH PERMISSION.

What changes have been made to labeling?

Patient profile. The so-called recommended patient profile has been streamlined. The label now indicates only that the LNG-IUS is recommended for women who have given birth to at least one child. A more detailed description of women who were included in the phase-II US clinical trial is included in that section of the labeling. Clinicians should recognize that neither nulliparity nor nulligravity is listed in labeling as a contraindication to the LNG-IUS.

Depth of cavity. Another important change in the new labeling is that the LNG-IUS can be used in women whose uterine cavity sounds to a depth of 6 to 10 cm (no longer only 6 to 9 cm). This will permit more multiparous women, who may have a larger cavity, to use the LNG-IUS.

Pregnancy risk and consequences. The risk of pregnancy is rare when the LNG-IUS is used; pregnancy with the device in situ does not appear to be associated with an increased risk of birth defects. As of September 2006, there had been only 390 live births among an estimated cumulative 9.9 million LNG-IUS users worldwide. Of those births, congenital anomalies have been infrequent; no clear trend was seen toward an increased risk of any specific anomaly after exposure to the LNG-IUS.

Adverse events. As worldwide experience with the LNG-IUS has expanded since the last labeling, the number of reported cases of relatively rare adverse events has also been updated:

• Only nine cases of infection with group A Streptococcus have been reported in 9.9 million users, constituting a risk of approximately one infection for every 1 million users
• Based on postmarketing experience, new wording has been added about the possibility of 1) device breakage (before insertion) and 2) angioedema—a rare allergic reaction that is not specific to levonorgestrel (or the IUS)
• Wording has been added to the labeling that provides reassurance, based on observational studies, that there is no evidence of an increase in the risk of breast cancer risk with use of the LNG-IUS
• Similarly, the new labeling declares that, in general, no adverse eff ects have been found with use of the LNG-IUS on breast-feeding performance in regard to the health, growth, or development of an infant—even though isolated cases of a decrease in milk production have been reported.

Contraindications. The roster of contraindications ( TABLE ) has been significantly modified to reflect scientific evidence. Removed from that list are 1) a history of ectopic pregnancy and 2) risk factors for ectopic pregnancy.

TABLE A new label lists 12 contraindications to the LNG-IUS

The LNG-IUS is contraindicated in the presence of one or more of the following:
Pregnancy or suspicion of pregnancy
Congenital or acquired uterine anomaly, including fibroids if they distort the uterine cavity
Acute pelvic inflammatory disease or a history of pelvic inflammatory disease, unless there has been a subsequent intrauterine pregnancy
Postpartum endometritis or infected abortion in the past 3 months
Known or suspected uterine or cervical neoplasia or unresolved, abnormal Pap smear
Genital bleeding of unknown cause
Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infection, until infection is controlled
Acute liver disease or liver tumor (benign or malignant
Conditions associated with an increased susceptibility to pelvic infection
Previously inserted intrauterine device that has not been removed
Hypersensitivity to any device component
Known or suspected carcinoma of the breast

 

Since the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena, Bayer Health Care Pharmaceuticals) ( FIGURE 1 ) was introduced in the United States in 2001, more than 2 million devices have been used by women here. This use has contributed to a cumulative experience of 14 million women (36 million woman-years of experience) in 120 countries over the last 18 years.

Recent Food and Drug Administration (FDA)-approved labeling changes for the LNG-IUS¹ expand the pool of women who are candidates for this convenient, reversible method of contraception. This article summarizes those labeling changes and answers questions that are often asked by clinicians who, more and more, insert the LNG-IUS for their patients.

FIGURE 1 LNG-IUS, arms open

The LNG-IUS device is readily visible on radiographs. Visualization by ultrasonography is more challenging.

SOURCE: BAYER HEALTH CARE PHARMACEUTICALS. USED WITH PERMISSION.

What changes have been made to labeling?

Patient profile. The so-called recommended patient profile has been streamlined. The label now indicates only that the LNG-IUS is recommended for women who have given birth to at least one child. A more detailed description of women who were included in the phase-II US clinical trial is included in that section of the labeling. Clinicians should recognize that neither nulliparity nor nulligravity is listed in labeling as a contraindication to the LNG-IUS.

Depth of cavity. Another important change in the new labeling is that the LNG-IUS can be used in women whose uterine cavity sounds to a depth of 6 to 10 cm (no longer only 6 to 9 cm). This will permit more multiparous women, who may have a larger cavity, to use the LNG-IUS.

Pregnancy risk and consequences. The risk of pregnancy is rare when the LNG-IUS is used; pregnancy with the device in situ does not appear to be associated with an increased risk of birth defects. As of September 2006, there had been only 390 live births among an estimated cumulative 9.9 million LNG-IUS users worldwide. Of those births, congenital anomalies have been infrequent; no clear trend was seen toward an increased risk of any specific anomaly after exposure to the LNG-IUS.

Adverse events. As worldwide experience with the LNG-IUS has expanded since the last labeling, the number of reported cases of relatively rare adverse events has also been updated:

• Only nine cases of infection with group A Streptococcus have been reported in 9.9 million users, constituting a risk of approximately one infection for every 1 million users
• Based on postmarketing experience, new wording has been added about the possibility of 1) device breakage (before insertion) and 2) angioedema—a rare allergic reaction that is not specific to levonorgestrel (or the IUS)
• Wording has been added to the labeling that provides reassurance, based on observational studies, that there is no evidence of an increase in the risk of breast cancer risk with use of the LNG-IUS
• Similarly, the new labeling declares that, in general, no adverse eff ects have been found with use of the LNG-IUS on breast-feeding performance in regard to the health, growth, or development of an infant—even though isolated cases of a decrease in milk production have been reported.

Contraindications. The roster of contraindications ( TABLE ) has been significantly modified to reflect scientific evidence. Removed from that list are 1) a history of ectopic pregnancy and 2) risk factors for ectopic pregnancy.

TABLE A new label lists 12 contraindications to the LNG-IUS

The LNG-IUS is contraindicated in the presence of one or more of the following:
Pregnancy or suspicion of pregnancy
Congenital or acquired uterine anomaly, including fibroids if they distort the uterine cavity
Acute pelvic inflammatory disease or a history of pelvic inflammatory disease, unless there has been a subsequent intrauterine pregnancy
Postpartum endometritis or infected abortion in the past 3 months
Known or suspected uterine or cervical neoplasia or unresolved, abnormal Pap smear
Genital bleeding of unknown cause
Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infection, until infection is controlled
Acute liver disease or liver tumor (benign or malignant
Conditions associated with an increased susceptibility to pelvic infection
Previously inserted intrauterine device that has not been removed
Hypersensitivity to any device component
Known or suspected carcinoma of the breast

 

Since the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena, Bayer Health Care Pharmaceuticals) ( FIGURE 1 ) was introduced in the United States in 2001, more than 2 million devices have been used by women here. This use has contributed to a cumulative experience of 14 million women (36 million woman-years of experience) in 120 countries over the last 18 years.

Recent Food and Drug Administration (FDA)-approved labeling changes for the LNG-IUS¹ expand the pool of women who are candidates for this convenient, reversible method of contraception. This article summarizes those labeling changes and answers questions that are often asked by clinicians who, more and more, insert the LNG-IUS for their patients.

FIGURE 1 LNG-IUS, arms open

The LNG-IUS device is readily visible on radiographs. Visualization by ultrasonography is more challenging.

SOURCE: BAYER HEALTH CARE PHARMACEUTICALS. USED WITH PERMISSION.

What changes have been made to labeling?

Patient profile. The so-called recommended patient profile has been streamlined. The label now indicates only that the LNG-IUS is recommended for women who have given birth to at least one child. A more detailed description of women who were included in the phase-II US clinical trial is included in that section of the labeling. Clinicians should recognize that neither nulliparity nor nulligravity is listed in labeling as a contraindication to the LNG-IUS.

Depth of cavity. Another important change in the new labeling is that the LNG-IUS can be used in women whose uterine cavity sounds to a depth of 6 to 10 cm (no longer only 6 to 9 cm). This will permit more multiparous women, who may have a larger cavity, to use the LNG-IUS.

Pregnancy risk and consequences. The risk of pregnancy is rare when the LNG-IUS is used; pregnancy with the device in situ does not appear to be associated with an increased risk of birth defects. As of September 2006, there had been only 390 live births among an estimated cumulative 9.9 million LNG-IUS users worldwide. Of those births, congenital anomalies have been infrequent; no clear trend was seen toward an increased risk of any specific anomaly after exposure to the LNG-IUS.

Adverse events. As worldwide experience with the LNG-IUS has expanded since the last labeling, the number of reported cases of relatively rare adverse events has also been updated:

• Only nine cases of infection with group A Streptococcus have been reported in 9.9 million users, constituting a risk of approximately one infection for every 1 million users
• Based on postmarketing experience, new wording has been added about the possibility of 1) device breakage (before insertion) and 2) angioedema—a rare allergic reaction that is not specific to levonorgestrel (or the IUS)
• Wording has been added to the labeling that provides reassurance, based on observational studies, that there is no evidence of an increase in the risk of breast cancer risk with use of the LNG-IUS
• Similarly, the new labeling declares that, in general, no adverse eff ects have been found with use of the LNG-IUS on breast-feeding performance in regard to the health, growth, or development of an infant—even though isolated cases of a decrease in milk production have been reported.

Contraindications. The roster of contraindications ( TABLE ) has been significantly modified to reflect scientific evidence. Removed from that list are 1) a history of ectopic pregnancy and 2) risk factors for ectopic pregnancy.

TABLE A new label lists 12 contraindications to the LNG-IUS

The LNG-IUS is contraindicated in the presence of one or more of the following:
Pregnancy or suspicion of pregnancy
Congenital or acquired uterine anomaly, including fibroids if they distort the uterine cavity
Acute pelvic inflammatory disease or a history of pelvic inflammatory disease, unless there has been a subsequent intrauterine pregnancy
Postpartum endometritis or infected abortion in the past 3 months
Known or suspected uterine or cervical neoplasia or unresolved, abnormal Pap smear
Genital bleeding of unknown cause
Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infection, until infection is controlled
Acute liver disease or liver tumor (benign or malignant
Conditions associated with an increased susceptibility to pelvic infection
Previously inserted intrauterine device that has not been removed
Hypersensitivity to any device component
Known or suspected carcinoma of the breast

 

Dr. Adamson is CEO of Advanced Reproductive Care Inc., and receives research support from IBSA.

The diagnosis and treatment of fertility are evolving rapidly as a result of clinical studies, scientific research, and changing socioeconomic and ethical perspectives. These developments benefit health-care consumers, but they also pose new challenges to general ObGyns and other practitioners committed to the best possible care for their patients.

In this Update, I focus on a number of these areas of change:

• care of women who have polycystic ovary syndrome (PCOS)
  
• the impact of myomas on fertility
  
• treatment of infertility in women who have endometriosis
  
• when tubal reconstruction is appropriate
  
• the impact of a woman’s age on fertility
  
• patient-friendly strategies to enhance fertility
  
• cross-border reproductive travel.
  

Use clomiphene citrate to stimulate ovulation in women who have PCOS

Practice Committee of the American Society for Reproductive Medicine. Use of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Fertil Steril. 2008;90(5 Suppl):S69–S73.

A new Committee Opinion from the American Society for Reproductive Medicine (ASRM) Practice Committee tackles the challenge of treating women with PCOS for infertility.

PCOS is associated with an increased risk of insulin resistance and diabetes mellitus. The first line of treatment for all women who have PCOS, especially those with an elevated body mass index, is lifestyle modification through diet and exercise, with the goal of losing weight.

Clomiphene is first-line therapy when ovulation is the aim

Metformin and other insulin-sensitizing agents may enhance ovulation and increase the response to clomiphene citrate in women who have PCOS and insulin resistance, but their use solely to enhance ovulation is unwarranted, and they do not reduce the rate of miscarriage. Clomiphene citrate should be the first-line treatment because it is much more effective. Long-term use of metformin to prevent disease is not advised.

Screen for insulin resistance at the time of diagnosis

Women who have PCOS should be given a 2-hour oral glucose tolerance test and have their lipid profile measured at the time of diagnosis and then at an interval of every 2 years. Insulin-sensitizing agents should be used for long-term health issues only after impaired glucose tolerance has been measured, if diet and exercise alone prove to be ineffective.

When choosing a treatment for myoma, consider impacts on fertility

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society of Reproduction Surgeons. Myomas and reproductive function. Fertil Steril. 2008;90(5 Suppl): S125–S130.

A recent educational bulletin from the ASRM Practice Committee examined the relationship between myomas and reproductive function and reviewed management of this pathology.

The effects of myomas on reproductive outcome are ill-defined, but fibroids that distort the uterine cavity, as well as larger intramural myomas, may have adverse effects on fertility.

Select interventions carefully

Among women who have infertility and those who have recurrent pregnancy loss, myomectomy should be considered only after thorough evaluation. The reason? Postoperative adhesions as a result of abdominal myomectomy are common and may reduce subsequent fertility.

As for uterine artery embolization, myolysis, and MRI-guided ultrasonic treatment, these are not recommended for women who have myomas and who are seeking to maintain or improve fertility. The safety and efficacy of these procedures in this population have not been established.

 

Is a GnRH agonist useful?

Treatment of myomas with a gonadotropin-releasing hormone (GnRH) agonist does not improve fertility but may be helpful before surgery in anemic women and in those who might be able to undergo a less invasive procedure if the myoma volume were moderately smaller.

Sequence of infertility treatments is critical in endometriosis patients

Adamson G. Management of endometriosis and infertility following surgery. In: Sutton C, Jones K, Adamson GD, eds. Modern Management of Endometriosis. London: Taylor & Francis; 2006:273–287.

New data make it easier to treat infertility in women thought to have endometriosis, although further randomized trials are needed. If other fertility variables are normal, and minimal to mild endometriosis is suspected but not confirmed, clomiphene citrate, 100 mg on cycle days 3 through 7, followed by intrauterine insemination (IUI) for 3 to 6 cycles, is a reasonable initial treatment, with the higher number of cycles being reserved for younger patients and those who have a better prognosis.

When is surgery helpful?

Diagnostic or operative laparoscopy, or both, is often indicated when one or more of the following are present:

• The patient experiences pain
  
• She fails to conceive after clomiphene citrate is administered and IUI is attempted for 3 to 6 cycles
  
• She has other factors associated with infertility.
  

If it is well performed, surgery is effective treatment for all stages of endometriosis, endometriomas, and disease of the cul de sac, for symptoms of pain or infertility, or both.

Generally, if pregnancy does not occur within 9 to 15 months after surgery, repeat surgery is of limited benefit for infertility, but may have some benefit for pain. In women who do not conceive after surgery, ovarian suppression for 2 months is of possible benefit before assisted reproductive technology (ART) and should be considered in patients who are also suffering from pain. Pre-ART surgery for large endometriomas is frequently indicated, and excision of the cyst capsule produces results superior to those of drainage, coagulation, or both.

Postoperative management

After complete destruction of endometriosis in women who have infertility, ovarian suppression is not indicated. Rather, the patient should usually attempt to conceive for 9 to 15 months, with an outside range of 3 to 24 months for much older women who have an unfavorable prognosis, and for much younger women who have a good prognosis, respectively. If pregnancy does not occur, clomiphene citrate and IUI for 3 to 6 months are then indicated.

If this last strategy is unsuccessful, the options include:

• gonadotropins and IUI for 3 months to a maximum of 6 months in the young patient who has a good prognosis
  
• repeat laparoscopy (although this option is rare), possibly in conjunction with gamete intrafallopian transfer (GIFT), or, alternatively, in vitro fertilization (IVF). If the patient had a technically inadequate operation the first time, it sometimes is appropriate to repeat the surgery or go directly to IVF.
  

Consider tubal reconstruction in carefully selected patients

Practice Committee of the American Society for Reproductive Medicine. The role of tubal reconstructive surgery in the era of assisted reproductive technologies. Fertil Steril. 2008;90(5 Suppl):S250–S253.

In the era of ART, tubal reconstruction has fewer indications but is still appropriate and effective in properly selected individuals.

Determine the extent of tubal disease before reconstructive surgery

Hysterosalpingography is a useful initial test for the evaluation of tubal patency, but laparoscopy often is necessary to identify the nature and extent of pelvic disease. Selective salpingography or hysteroscopic tubal recanalization can help confirm the diagnosis of true proximal tubal occlusion.

Advise the patient of risks of surgery

Generally, the risk of ectopic pregnancy after tubal reconstruction is comparable to the risk of ectopic pregnancy associated with IVF, but the extent of tubal disease and pelvic pathology are important variables in predicting intrauterine and ectopic pregnancy rates.

The pregnancy rate after reversal of tubal sterilization depends on 1) the type of sterilization procedure that was performed, 2) site of anastomosis, and 3) postoperative tubal length, as well as 4) sperm quality and 5) the age of the female patient.

Maternal age, number of children desired, coexisting infertility variables, risk of ectopic and multiple pregnancy, and treatment cost are important considerations when counseling patients about the relative advantages and disadvantages of tubal surgery and IVF.

IVF is the best treatment for older women of reproductive age who have significant tubal pathology, and for women who have both proximal and distal occlusion.

Age, and duration of infertility, are key determinants of treatment

Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists, and Practice Committee of the American Society for Reproductive Medicine. Age-related fertility decline: a Committee Opinion. Fertil Steril. 2008;90(5 Suppl):S154–S155.

 

Women older than 35 years should receive expedited evaluation and treatment for infertility if they have not conceived after 6 months, or earlier if clinically indicated. That’s one of the conclusions from a recent ACOG–ASRM joint Committee Opinion on age-related fertility decline.

Age remains a major variable influencing a woman’s fertility and risk of pregnancy loss, and is increasingly important because of the social trend toward deferred child-bearing. The fertility rate peaks in a woman’s mid-20s and decreases by approximately 25% by age 35 and 50% by age 40, with a concomitant (and significant) increase in rates of aneuploidy and miscarriage.

The duration of infertility also is key. Of any given 100 women attempting to conceive:

• 78 will succeed within 1 year
  
• 88 will conceive within 2 years
  
• only an additional two or three women will conceive in the third year
  
• one more will conceive in each of the fourth and fifth years
  
• only three more will conceive over the rest of their reproductive life.
  

These data suggest that infertility should be investigated after 12 or more months of regular unprotected intercourse, with earlier evaluation and treatment for women who are older than 35 years.

Recurrent pregnancy loss and infertility are separate entities

By definition, recurrent pregnancy loss entails the loss of two or more pregnancies. When the cause is unknown, each loss merits careful review to determine whether specific evaluation may be appropriate. After three losses, thorough evaluation is warranted.^1,2

To distinguish infertility from recurrent pregnancy loss, define clinical pregnancy as one documented by US or histopathology.

New technologies remain unproven

Although ovarian tissue and oocyte cryopreservation offer the promise of female fertility preservation, these technologies remain investigational to date.

The greatest benefit to patients who wish to preserve their fertility is appropriate counseling about their reproductive health.^{3, 4}

Fertility can be enhanced with a few patient-friendly strategies

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility. Optimizing natural fertility. Fertil Steril. 2008;90(5 Suppl):S1–S6.

Another Committee Opinion from ASRM, in collaboration with the Society for Reproductive Endocrinology and Infertility, offers simple but effective steps for patients to take to optimize fertility. ObGyns should recommend these strategies to any woman planning to conceive in the near future.

Frequent intercourse is best

Intercourse every day or every other day yields the highest pregnancy rate, but intercourse two to three times a week is nearly equivalent. There is a “fertile window” that spans the 6-day interval ending on the day of ovulation, and it correlates with the volume and character of cervical mucus.

Among women who have regular menstrual cycles, frequent intercourse that begins soon after the cessation of menses can help maximize fecundity.

Devices that determine or predict the time of ovulation may be useful for couples who have infrequent intercourse.

Neither specific coital timing, nor position during coitus, nor rest in a supine position after intercourse has a significant impact on fertility.

Caffeine, alcohol OK—in moderation

Moderate caffeine or alcohol consumption (1 or 2 drinks daily) has no demonstrable adverse effect on fertility. Smoking, a higher level of alcohol consumption (≥2 drinks daily), use of recreational drugs, and most commercially available vaginal lubricants should be discouraged among patients who are trying to conceive.

Fertility rates are lower in women who are very thin or obese, but there is little evidence that dietary variations improve fertility or affect the gender of the infant.

Elevated blood mercury levels from heavy seafood consumption have been associated with infertility.

Saunas do not reduce fertility in women. In normal men, attempts to protect the testicles from excessive heat are unjustified.

Avoid solvents and pesticides

• Fecundity may be diminished in women who are exposed to certain toxins and solvents, such as those used in the dry-cleaning and printing industries.
  
• Men who are exposed to heavy metals may be more likely to have abnormal semen parameters.
  
• Pesticide exposure may be a problem for both male and female agricultural workers.
  
• Despite limited data on exposure to lead and use of industrial microwaves, they are probably best avoided or minimized.
  
• Prescription drug use should be carefully controlled and managed on an individual basis.
  

Recommend 400 µg of folic acid daily

Any woman hoping to conceive should be advised to initiate this regimen to reduce the risk of neural tube defects.

 

More and more women seek care in countries other than their own

“Medical tourism” is an interesting phenomenon that has received widespread media attention. When it applies to infertility, a more appropriate term may be “cross-border reproductive care.”

This is an international phenomenon that is, so far, poorly documented. Common reasons to travel for medical care include cost and availability of specialized services. Women grappling with infertility may also seek to bypass regulations or ethical issues that limit availability of treatment in their home country. Among the issues that prompt travel are:

• gamete and embryo donation
  
• payment of donors and surrogates
  
• nontraditional relationships.
  

The Canadian government hosted the first international symposium on cross-border reproductive care last month in an effort to learn more about this complex issue and identify ways to ensure the quality and safety of such services.

Dr. Adamson is CEO of Advanced Reproductive Care Inc., and receives research support from IBSA.

The diagnosis and treatment of fertility are evolving rapidly as a result of clinical studies, scientific research, and changing socioeconomic and ethical perspectives. These developments benefit health-care consumers, but they also pose new challenges to general ObGyns and other practitioners committed to the best possible care for their patients.

In this Update, I focus on a number of these areas of change:

• care of women who have polycystic ovary syndrome (PCOS)
  
• the impact of myomas on fertility
  
• treatment of infertility in women who have endometriosis
  
• when tubal reconstruction is appropriate
  
• the impact of a woman’s age on fertility
  
• patient-friendly strategies to enhance fertility
  
• cross-border reproductive travel.
  

Use clomiphene citrate to stimulate ovulation in women who have PCOS

Practice Committee of the American Society for Reproductive Medicine. Use of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Fertil Steril. 2008;90(5 Suppl):S69–S73.

A new Committee Opinion from the American Society for Reproductive Medicine (ASRM) Practice Committee tackles the challenge of treating women with PCOS for infertility.

PCOS is associated with an increased risk of insulin resistance and diabetes mellitus. The first line of treatment for all women who have PCOS, especially those with an elevated body mass index, is lifestyle modification through diet and exercise, with the goal of losing weight.

Clomiphene is first-line therapy when ovulation is the aim

Metformin and other insulin-sensitizing agents may enhance ovulation and increase the response to clomiphene citrate in women who have PCOS and insulin resistance, but their use solely to enhance ovulation is unwarranted, and they do not reduce the rate of miscarriage. Clomiphene citrate should be the first-line treatment because it is much more effective. Long-term use of metformin to prevent disease is not advised.

Screen for insulin resistance at the time of diagnosis

Women who have PCOS should be given a 2-hour oral glucose tolerance test and have their lipid profile measured at the time of diagnosis and then at an interval of every 2 years. Insulin-sensitizing agents should be used for long-term health issues only after impaired glucose tolerance has been measured, if diet and exercise alone prove to be ineffective.

When choosing a treatment for myoma, consider impacts on fertility

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society of Reproduction Surgeons. Myomas and reproductive function. Fertil Steril. 2008;90(5 Suppl): S125–S130.

A recent educational bulletin from the ASRM Practice Committee examined the relationship between myomas and reproductive function and reviewed management of this pathology.

The effects of myomas on reproductive outcome are ill-defined, but fibroids that distort the uterine cavity, as well as larger intramural myomas, may have adverse effects on fertility.

Select interventions carefully

Among women who have infertility and those who have recurrent pregnancy loss, myomectomy should be considered only after thorough evaluation. The reason? Postoperative adhesions as a result of abdominal myomectomy are common and may reduce subsequent fertility.

As for uterine artery embolization, myolysis, and MRI-guided ultrasonic treatment, these are not recommended for women who have myomas and who are seeking to maintain or improve fertility. The safety and efficacy of these procedures in this population have not been established.

 

Is a GnRH agonist useful?

Treatment of myomas with a gonadotropin-releasing hormone (GnRH) agonist does not improve fertility but may be helpful before surgery in anemic women and in those who might be able to undergo a less invasive procedure if the myoma volume were moderately smaller.

Sequence of infertility treatments is critical in endometriosis patients

Adamson G. Management of endometriosis and infertility following surgery. In: Sutton C, Jones K, Adamson GD, eds. Modern Management of Endometriosis. London: Taylor & Francis; 2006:273–287.

New data make it easier to treat infertility in women thought to have endometriosis, although further randomized trials are needed. If other fertility variables are normal, and minimal to mild endometriosis is suspected but not confirmed, clomiphene citrate, 100 mg on cycle days 3 through 7, followed by intrauterine insemination (IUI) for 3 to 6 cycles, is a reasonable initial treatment, with the higher number of cycles being reserved for younger patients and those who have a better prognosis.

When is surgery helpful?

Diagnostic or operative laparoscopy, or both, is often indicated when one or more of the following are present:

• The patient experiences pain
  
• She fails to conceive after clomiphene citrate is administered and IUI is attempted for 3 to 6 cycles
  
• She has other factors associated with infertility.
  

If it is well performed, surgery is effective treatment for all stages of endometriosis, endometriomas, and disease of the cul de sac, for symptoms of pain or infertility, or both.

Generally, if pregnancy does not occur within 9 to 15 months after surgery, repeat surgery is of limited benefit for infertility, but may have some benefit for pain. In women who do not conceive after surgery, ovarian suppression for 2 months is of possible benefit before assisted reproductive technology (ART) and should be considered in patients who are also suffering from pain. Pre-ART surgery for large endometriomas is frequently indicated, and excision of the cyst capsule produces results superior to those of drainage, coagulation, or both.

Postoperative management

After complete destruction of endometriosis in women who have infertility, ovarian suppression is not indicated. Rather, the patient should usually attempt to conceive for 9 to 15 months, with an outside range of 3 to 24 months for much older women who have an unfavorable prognosis, and for much younger women who have a good prognosis, respectively. If pregnancy does not occur, clomiphene citrate and IUI for 3 to 6 months are then indicated.

If this last strategy is unsuccessful, the options include:

• gonadotropins and IUI for 3 months to a maximum of 6 months in the young patient who has a good prognosis
  
• repeat laparoscopy (although this option is rare), possibly in conjunction with gamete intrafallopian transfer (GIFT), or, alternatively, in vitro fertilization (IVF). If the patient had a technically inadequate operation the first time, it sometimes is appropriate to repeat the surgery or go directly to IVF.
  

Consider tubal reconstruction in carefully selected patients

Practice Committee of the American Society for Reproductive Medicine. The role of tubal reconstructive surgery in the era of assisted reproductive technologies. Fertil Steril. 2008;90(5 Suppl):S250–S253.

In the era of ART, tubal reconstruction has fewer indications but is still appropriate and effective in properly selected individuals.

Determine the extent of tubal disease before reconstructive surgery

Hysterosalpingography is a useful initial test for the evaluation of tubal patency, but laparoscopy often is necessary to identify the nature and extent of pelvic disease. Selective salpingography or hysteroscopic tubal recanalization can help confirm the diagnosis of true proximal tubal occlusion.

Advise the patient of risks of surgery

Generally, the risk of ectopic pregnancy after tubal reconstruction is comparable to the risk of ectopic pregnancy associated with IVF, but the extent of tubal disease and pelvic pathology are important variables in predicting intrauterine and ectopic pregnancy rates.

The pregnancy rate after reversal of tubal sterilization depends on 1) the type of sterilization procedure that was performed, 2) site of anastomosis, and 3) postoperative tubal length, as well as 4) sperm quality and 5) the age of the female patient.

Maternal age, number of children desired, coexisting infertility variables, risk of ectopic and multiple pregnancy, and treatment cost are important considerations when counseling patients about the relative advantages and disadvantages of tubal surgery and IVF.

IVF is the best treatment for older women of reproductive age who have significant tubal pathology, and for women who have both proximal and distal occlusion.

Age, and duration of infertility, are key determinants of treatment

Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists, and Practice Committee of the American Society for Reproductive Medicine. Age-related fertility decline: a Committee Opinion. Fertil Steril. 2008;90(5 Suppl):S154–S155.

 

Women older than 35 years should receive expedited evaluation and treatment for infertility if they have not conceived after 6 months, or earlier if clinically indicated. That’s one of the conclusions from a recent ACOG–ASRM joint Committee Opinion on age-related fertility decline.

Age remains a major variable influencing a woman’s fertility and risk of pregnancy loss, and is increasingly important because of the social trend toward deferred child-bearing. The fertility rate peaks in a woman’s mid-20s and decreases by approximately 25% by age 35 and 50% by age 40, with a concomitant (and significant) increase in rates of aneuploidy and miscarriage.

The duration of infertility also is key. Of any given 100 women attempting to conceive:

• 78 will succeed within 1 year
  
• 88 will conceive within 2 years
  
• only an additional two or three women will conceive in the third year
  
• one more will conceive in each of the fourth and fifth years
  
• only three more will conceive over the rest of their reproductive life.
  

These data suggest that infertility should be investigated after 12 or more months of regular unprotected intercourse, with earlier evaluation and treatment for women who are older than 35 years.

Recurrent pregnancy loss and infertility are separate entities

By definition, recurrent pregnancy loss entails the loss of two or more pregnancies. When the cause is unknown, each loss merits careful review to determine whether specific evaluation may be appropriate. After three losses, thorough evaluation is warranted.^1,2

To distinguish infertility from recurrent pregnancy loss, define clinical pregnancy as one documented by US or histopathology.

New technologies remain unproven

Although ovarian tissue and oocyte cryopreservation offer the promise of female fertility preservation, these technologies remain investigational to date.

The greatest benefit to patients who wish to preserve their fertility is appropriate counseling about their reproductive health.^{3, 4}

Fertility can be enhanced with a few patient-friendly strategies

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility. Optimizing natural fertility. Fertil Steril. 2008;90(5 Suppl):S1–S6.

Another Committee Opinion from ASRM, in collaboration with the Society for Reproductive Endocrinology and Infertility, offers simple but effective steps for patients to take to optimize fertility. ObGyns should recommend these strategies to any woman planning to conceive in the near future.

Frequent intercourse is best

Intercourse every day or every other day yields the highest pregnancy rate, but intercourse two to three times a week is nearly equivalent. There is a “fertile window” that spans the 6-day interval ending on the day of ovulation, and it correlates with the volume and character of cervical mucus.

Among women who have regular menstrual cycles, frequent intercourse that begins soon after the cessation of menses can help maximize fecundity.

Devices that determine or predict the time of ovulation may be useful for couples who have infrequent intercourse.

Neither specific coital timing, nor position during coitus, nor rest in a supine position after intercourse has a significant impact on fertility.

Caffeine, alcohol OK—in moderation

Moderate caffeine or alcohol consumption (1 or 2 drinks daily) has no demonstrable adverse effect on fertility. Smoking, a higher level of alcohol consumption (≥2 drinks daily), use of recreational drugs, and most commercially available vaginal lubricants should be discouraged among patients who are trying to conceive.

Fertility rates are lower in women who are very thin or obese, but there is little evidence that dietary variations improve fertility or affect the gender of the infant.

Elevated blood mercury levels from heavy seafood consumption have been associated with infertility.

Saunas do not reduce fertility in women. In normal men, attempts to protect the testicles from excessive heat are unjustified.

Avoid solvents and pesticides

• Fecundity may be diminished in women who are exposed to certain toxins and solvents, such as those used in the dry-cleaning and printing industries.
  
• Men who are exposed to heavy metals may be more likely to have abnormal semen parameters.
  
• Pesticide exposure may be a problem for both male and female agricultural workers.
  
• Despite limited data on exposure to lead and use of industrial microwaves, they are probably best avoided or minimized.
  
• Prescription drug use should be carefully controlled and managed on an individual basis.
  

Recommend 400 µg of folic acid daily

Any woman hoping to conceive should be advised to initiate this regimen to reduce the risk of neural tube defects.

 

More and more women seek care in countries other than their own

“Medical tourism” is an interesting phenomenon that has received widespread media attention. When it applies to infertility, a more appropriate term may be “cross-border reproductive care.”

This is an international phenomenon that is, so far, poorly documented. Common reasons to travel for medical care include cost and availability of specialized services. Women grappling with infertility may also seek to bypass regulations or ethical issues that limit availability of treatment in their home country. Among the issues that prompt travel are:

• gamete and embryo donation
  
• payment of donors and surrogates
  
• nontraditional relationships.
  

The Canadian government hosted the first international symposium on cross-border reproductive care last month in an effort to learn more about this complex issue and identify ways to ensure the quality and safety of such services.

Dr. Adamson is CEO of Advanced Reproductive Care Inc., and receives research support from IBSA.

The diagnosis and treatment of fertility are evolving rapidly as a result of clinical studies, scientific research, and changing socioeconomic and ethical perspectives. These developments benefit health-care consumers, but they also pose new challenges to general ObGyns and other practitioners committed to the best possible care for their patients.

In this Update, I focus on a number of these areas of change:

• care of women who have polycystic ovary syndrome (PCOS)
  
• the impact of myomas on fertility
  
• treatment of infertility in women who have endometriosis
  
• when tubal reconstruction is appropriate
  
• the impact of a woman’s age on fertility
  
• patient-friendly strategies to enhance fertility
  
• cross-border reproductive travel.
  

Use clomiphene citrate to stimulate ovulation in women who have PCOS

Practice Committee of the American Society for Reproductive Medicine. Use of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Fertil Steril. 2008;90(5 Suppl):S69–S73.

A new Committee Opinion from the American Society for Reproductive Medicine (ASRM) Practice Committee tackles the challenge of treating women with PCOS for infertility.

PCOS is associated with an increased risk of insulin resistance and diabetes mellitus. The first line of treatment for all women who have PCOS, especially those with an elevated body mass index, is lifestyle modification through diet and exercise, with the goal of losing weight.

Clomiphene is first-line therapy when ovulation is the aim

Metformin and other insulin-sensitizing agents may enhance ovulation and increase the response to clomiphene citrate in women who have PCOS and insulin resistance, but their use solely to enhance ovulation is unwarranted, and they do not reduce the rate of miscarriage. Clomiphene citrate should be the first-line treatment because it is much more effective. Long-term use of metformin to prevent disease is not advised.

Screen for insulin resistance at the time of diagnosis

Women who have PCOS should be given a 2-hour oral glucose tolerance test and have their lipid profile measured at the time of diagnosis and then at an interval of every 2 years. Insulin-sensitizing agents should be used for long-term health issues only after impaired glucose tolerance has been measured, if diet and exercise alone prove to be ineffective.

When choosing a treatment for myoma, consider impacts on fertility

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society of Reproduction Surgeons. Myomas and reproductive function. Fertil Steril. 2008;90(5 Suppl): S125–S130.

A recent educational bulletin from the ASRM Practice Committee examined the relationship between myomas and reproductive function and reviewed management of this pathology.

The effects of myomas on reproductive outcome are ill-defined, but fibroids that distort the uterine cavity, as well as larger intramural myomas, may have adverse effects on fertility.

Select interventions carefully

Among women who have infertility and those who have recurrent pregnancy loss, myomectomy should be considered only after thorough evaluation. The reason? Postoperative adhesions as a result of abdominal myomectomy are common and may reduce subsequent fertility.

As for uterine artery embolization, myolysis, and MRI-guided ultrasonic treatment, these are not recommended for women who have myomas and who are seeking to maintain or improve fertility. The safety and efficacy of these procedures in this population have not been established.

 

Is a GnRH agonist useful?

Treatment of myomas with a gonadotropin-releasing hormone (GnRH) agonist does not improve fertility but may be helpful before surgery in anemic women and in those who might be able to undergo a less invasive procedure if the myoma volume were moderately smaller.

Sequence of infertility treatments is critical in endometriosis patients

Adamson G. Management of endometriosis and infertility following surgery. In: Sutton C, Jones K, Adamson GD, eds. Modern Management of Endometriosis. London: Taylor & Francis; 2006:273–287.

New data make it easier to treat infertility in women thought to have endometriosis, although further randomized trials are needed. If other fertility variables are normal, and minimal to mild endometriosis is suspected but not confirmed, clomiphene citrate, 100 mg on cycle days 3 through 7, followed by intrauterine insemination (IUI) for 3 to 6 cycles, is a reasonable initial treatment, with the higher number of cycles being reserved for younger patients and those who have a better prognosis.

When is surgery helpful?

Diagnostic or operative laparoscopy, or both, is often indicated when one or more of the following are present:

• The patient experiences pain
  
• She fails to conceive after clomiphene citrate is administered and IUI is attempted for 3 to 6 cycles
  
• She has other factors associated with infertility.
  

If it is well performed, surgery is effective treatment for all stages of endometriosis, endometriomas, and disease of the cul de sac, for symptoms of pain or infertility, or both.

Generally, if pregnancy does not occur within 9 to 15 months after surgery, repeat surgery is of limited benefit for infertility, but may have some benefit for pain. In women who do not conceive after surgery, ovarian suppression for 2 months is of possible benefit before assisted reproductive technology (ART) and should be considered in patients who are also suffering from pain. Pre-ART surgery for large endometriomas is frequently indicated, and excision of the cyst capsule produces results superior to those of drainage, coagulation, or both.

Postoperative management

After complete destruction of endometriosis in women who have infertility, ovarian suppression is not indicated. Rather, the patient should usually attempt to conceive for 9 to 15 months, with an outside range of 3 to 24 months for much older women who have an unfavorable prognosis, and for much younger women who have a good prognosis, respectively. If pregnancy does not occur, clomiphene citrate and IUI for 3 to 6 months are then indicated.

If this last strategy is unsuccessful, the options include:

• gonadotropins and IUI for 3 months to a maximum of 6 months in the young patient who has a good prognosis
  
• repeat laparoscopy (although this option is rare), possibly in conjunction with gamete intrafallopian transfer (GIFT), or, alternatively, in vitro fertilization (IVF). If the patient had a technically inadequate operation the first time, it sometimes is appropriate to repeat the surgery or go directly to IVF.
  

Consider tubal reconstruction in carefully selected patients

Practice Committee of the American Society for Reproductive Medicine. The role of tubal reconstructive surgery in the era of assisted reproductive technologies. Fertil Steril. 2008;90(5 Suppl):S250–S253.

In the era of ART, tubal reconstruction has fewer indications but is still appropriate and effective in properly selected individuals.

Determine the extent of tubal disease before reconstructive surgery

Hysterosalpingography is a useful initial test for the evaluation of tubal patency, but laparoscopy often is necessary to identify the nature and extent of pelvic disease. Selective salpingography or hysteroscopic tubal recanalization can help confirm the diagnosis of true proximal tubal occlusion.

Advise the patient of risks of surgery

Generally, the risk of ectopic pregnancy after tubal reconstruction is comparable to the risk of ectopic pregnancy associated with IVF, but the extent of tubal disease and pelvic pathology are important variables in predicting intrauterine and ectopic pregnancy rates.

The pregnancy rate after reversal of tubal sterilization depends on 1) the type of sterilization procedure that was performed, 2) site of anastomosis, and 3) postoperative tubal length, as well as 4) sperm quality and 5) the age of the female patient.

Maternal age, number of children desired, coexisting infertility variables, risk of ectopic and multiple pregnancy, and treatment cost are important considerations when counseling patients about the relative advantages and disadvantages of tubal surgery and IVF.

IVF is the best treatment for older women of reproductive age who have significant tubal pathology, and for women who have both proximal and distal occlusion.

Age, and duration of infertility, are key determinants of treatment

Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists, and Practice Committee of the American Society for Reproductive Medicine. Age-related fertility decline: a Committee Opinion. Fertil Steril. 2008;90(5 Suppl):S154–S155.

 

Women older than 35 years should receive expedited evaluation and treatment for infertility if they have not conceived after 6 months, or earlier if clinically indicated. That’s one of the conclusions from a recent ACOG–ASRM joint Committee Opinion on age-related fertility decline.

Age remains a major variable influencing a woman’s fertility and risk of pregnancy loss, and is increasingly important because of the social trend toward deferred child-bearing. The fertility rate peaks in a woman’s mid-20s and decreases by approximately 25% by age 35 and 50% by age 40, with a concomitant (and significant) increase in rates of aneuploidy and miscarriage.

The duration of infertility also is key. Of any given 100 women attempting to conceive:

• 78 will succeed within 1 year
  
• 88 will conceive within 2 years
  
• only an additional two or three women will conceive in the third year
  
• one more will conceive in each of the fourth and fifth years
  
• only three more will conceive over the rest of their reproductive life.
  

These data suggest that infertility should be investigated after 12 or more months of regular unprotected intercourse, with earlier evaluation and treatment for women who are older than 35 years.

Recurrent pregnancy loss and infertility are separate entities

By definition, recurrent pregnancy loss entails the loss of two or more pregnancies. When the cause is unknown, each loss merits careful review to determine whether specific evaluation may be appropriate. After three losses, thorough evaluation is warranted.^1,2

To distinguish infertility from recurrent pregnancy loss, define clinical pregnancy as one documented by US or histopathology.

New technologies remain unproven

Although ovarian tissue and oocyte cryopreservation offer the promise of female fertility preservation, these technologies remain investigational to date.

The greatest benefit to patients who wish to preserve their fertility is appropriate counseling about their reproductive health.^{3, 4}

Fertility can be enhanced with a few patient-friendly strategies

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility. Optimizing natural fertility. Fertil Steril. 2008;90(5 Suppl):S1–S6.

Another Committee Opinion from ASRM, in collaboration with the Society for Reproductive Endocrinology and Infertility, offers simple but effective steps for patients to take to optimize fertility. ObGyns should recommend these strategies to any woman planning to conceive in the near future.

Frequent intercourse is best

Intercourse every day or every other day yields the highest pregnancy rate, but intercourse two to three times a week is nearly equivalent. There is a “fertile window” that spans the 6-day interval ending on the day of ovulation, and it correlates with the volume and character of cervical mucus.

Among women who have regular menstrual cycles, frequent intercourse that begins soon after the cessation of menses can help maximize fecundity.

Devices that determine or predict the time of ovulation may be useful for couples who have infrequent intercourse.

Neither specific coital timing, nor position during coitus, nor rest in a supine position after intercourse has a significant impact on fertility.

Caffeine, alcohol OK—in moderation

Moderate caffeine or alcohol consumption (1 or 2 drinks daily) has no demonstrable adverse effect on fertility. Smoking, a higher level of alcohol consumption (≥2 drinks daily), use of recreational drugs, and most commercially available vaginal lubricants should be discouraged among patients who are trying to conceive.

Fertility rates are lower in women who are very thin or obese, but there is little evidence that dietary variations improve fertility or affect the gender of the infant.

Elevated blood mercury levels from heavy seafood consumption have been associated with infertility.

Saunas do not reduce fertility in women. In normal men, attempts to protect the testicles from excessive heat are unjustified.

Avoid solvents and pesticides

• Fecundity may be diminished in women who are exposed to certain toxins and solvents, such as those used in the dry-cleaning and printing industries.
  
• Men who are exposed to heavy metals may be more likely to have abnormal semen parameters.
  
• Pesticide exposure may be a problem for both male and female agricultural workers.
  
• Despite limited data on exposure to lead and use of industrial microwaves, they are probably best avoided or minimized.
  
• Prescription drug use should be carefully controlled and managed on an individual basis.
  

Recommend 400 µg of folic acid daily

Any woman hoping to conceive should be advised to initiate this regimen to reduce the risk of neural tube defects.

 

More and more women seek care in countries other than their own

“Medical tourism” is an interesting phenomenon that has received widespread media attention. When it applies to infertility, a more appropriate term may be “cross-border reproductive care.”

This is an international phenomenon that is, so far, poorly documented. Common reasons to travel for medical care include cost and availability of specialized services. Women grappling with infertility may also seek to bypass regulations or ethical issues that limit availability of treatment in their home country. Among the issues that prompt travel are:

• gamete and embryo donation
  
• payment of donors and surrogates
  
• nontraditional relationships.
  

The Canadian government hosted the first international symposium on cross-border reproductive care last month in an effort to learn more about this complex issue and identify ways to ensure the quality and safety of such services.

The authors report no financial relationships relevant to this article.

Hear Dr Phillips discuss the key points of this series

With the ranks of the obese expanding, and the severity of obesity increasing as well, obstetricians see a greater percentage of obese and morbidly obese gravidas in their practice. At the end of pregnancy, when it is time to deliver the infant, a number of issues must be taken into account to ensure the safety and health of both mother and child. Part 2 of this two-part article discusses these issues, from intrapartum and intraoperative considerations to care during the postpartum period.

Intrapartum concerns

Induction of labor

Obese women are more likely to require induction of labor; they should be counseled accordingly. The rate of labor induction is as high as 35% in women who have a body mass index (BMI) above 35.¹ Many of these inductions are indicated for maternal disease such as diabetes or preeclampsia. However, data suggest that obesity alone increases the induction rate, possibly through increased levels of leptin (an adipokine involved in obesity, appetite, and satiety), which may inhibit uterine contractions.²

Uterine and fetal monitoring

Monitoring of uterine contractions and fetal heart rate can be challenging in obese women. Early use of an intra uterine pressure catheter and fetal scalp electrode can help.

Shoulder dystocia

Obesity is a risk factor for macrosomia, which increases the likelihood of shoulder dystocia. In addition, at least one study supports maternal obesity as an independent risk factor for shoulder dystocia. Women who had a BMI above 30 were 2.7 times more likely to have a pregnancy complicated by shoulder dystocia, after adjustment for macrosomia, diabetes, parity, and induction of labor.³

Because of this risk, appropriate staff should be readily available for assistance, and operative vaginal delivery should be performed with caution, if at all.

Vaginal birth after cesarean delivery

Obese women who have a history of cesarean delivery need to be counseled about the higher risk of failed vaginal birth after cesarean (VBAC) and the likely need for repeat cesarean delivery. They also need to be told about the elevated risk of infection in the event that VBAC fails.

In women of normal weight, the likelihood of successful VBAC exceeds 80%, compared with a success rate of 68% for women who have a BMI above 29, and 60% for women who have a BMI above 40.^4,5

Appropriate counseling and patient selection are critical components of the decision to proceed with a trial of labor in obese women who have a history of cesarean delivery. Twenty-four-hour anesthesia and NICU coverage are also necessary in case emergent cesarean delivery becomes necessary.

Cesarean delivery

Morbidly obese women (BMI >35) have approximately a 50% greater chance of requiring cesarean delivery than do women of normal weight.⁶ The need for cesarean delivery rises with increasing BMI, probably because of a greater degree of maternal pelvic soft tissue, which increases the risk of both dystocia and cephalopelvic disproportion.

Anesthesia

It may be advisable to place an early epidural in laboring obese patients because they are more likely to require multiple placement attempts and cesarean delivery.

Intraoperative considerations

Ensure availability of the proper equipment

Table extenders, appropriate retractors, and long instruments should be readily available before surgery. For example, obstetricians often retract the panniculus to allow for a Pfannenstiel skin incision ( FIGURE 1 ), which works well to increase exposure. Moreover, the depth of the abdominal wall is much thinner beneath the panniculus.

However, be aware that, even in a supine patient with a leftward tilt, the weight of the panniculus can decrease vena caval return and cause uteroplacental insufficiency and compromised maternal respiration. Cesarean delivery should be performed expediently for these reasons.

A self-retaining elastic abdominal retractor may improve exposure at the same time that it minimizes the amount of retraction that must be exerted by the surgical assistant ( FIGURE 2 ).

FIGURE 1 Retract the panniculus

Retract the panniculus toward the patient’s head and use straps to secure it to facilitate a Pfannenstiel incision.

FIGURE 2 Elastic abdominal retractor improves visibility and access

Insert the inner ring of the adjustable elastic retractor into the abdominal cavity toward the patient’s head until it springs open against the parietal peritoneum. The outer ring is then rolled onto the plastic sleeve until it is snug against the skin.

 

Prophylaxis is warranted

Preoperative prophylactic antibiotics (weight-based) and prophylaxis for venous thromboembolism using sequential compression devices are recommended prior to surgery.

Choose the incision wisely

Data do not indicate whether vertical or transverse skin incisions for cesarean delivery are associated with higher infectious morbidity. In general, a Pfannenstiel incision is associated with less postoperative discomfort, allowing earlier mobilization and better respiratory function. A vertical incision allows optimal exposure, especially in the case of a macrosomic infant, and may thereby limit operating time and blood loss.^7,8

A vertical supraumbilical incision is another option. If the lower uterine segment is not accessible, a fundal uterine incision can be made ( FIGURE 3 ). The advantage of this method is increased exposure as well as access to the incision for wound care. However, because this method may necessitate a classical uterine incision, counseling must be given regarding future pregnancy.

FIGURE 3 Pair incisions strategically to ease cesarean delivery

In an obese patient, a supraumbilical skin incision paired with a classical uterine incision may simplify the surgery.

Other intraoperative considerations

If the surgery is prolonged, consider administering another dose of antibiotics.

If the subcutaneous tissue is thicker than 2 cm, it should be reapproximated to minimize the risk of hematoma and seroma formation and wound infection.^8,9

A subcutaneous drain should also be considered.

Postpartum care

Be aware of special risks

One retrospective study showed an increased risk of postpartum hemorrhage in women who had a BMI above 25, compared with women of normal weight. This risk increased as BMI increased. Knowledge of this complication and early use of uterotonic agents can minimize the morbidity associated with postpartum hemorrhage.

Postpartum infection is more likely in obese women, with three times the risk of endometritis of women of normal weight, and increased risks of wound infection, urinary tract infection, septic pelvic thrombophlebitis, and pneumonia.¹⁰ Early recognition of infection and administration of antibiotics can minimize morbidity.

Venous thromboembolism is more likely throughout pregnancy in obese women. Risk is heightened, however, during the postpartum period, when it is four times as high as the risk in women of normal weight.¹¹ Early ambulation and use of venous compression devices are encouraged. Consider heparin in the immediate postpartum period, when mobility is compromised for a longer period, particularly for women undergoing cesarean delivery who have comorbidities.

Suggest breastfeeding, weight loss

Women who breastfeed longer than 1 month have a 22% reduction in the risk of developing metabolic syndrome later in life, compared with women who do not. It also appears that a longer duration of breastfeeding reduces the risk of diabetes.¹²

Weight loss should be strongly encouraged. Women who retained their pregnancy weight at 6 months were 18 lb heavier after 10 years than women who lost their pregnancy weight.

The risk of metabolic syndrome increases with parity, probably because of the tendency of many obese women to retain their pregnancy weight.¹²

The authors report no financial relationships relevant to this article.

Hear Dr Phillips discuss the key points of this series

With the ranks of the obese expanding, and the severity of obesity increasing as well, obstetricians see a greater percentage of obese and morbidly obese gravidas in their practice. At the end of pregnancy, when it is time to deliver the infant, a number of issues must be taken into account to ensure the safety and health of both mother and child. Part 2 of this two-part article discusses these issues, from intrapartum and intraoperative considerations to care during the postpartum period.

Intrapartum concerns

Induction of labor

Obese women are more likely to require induction of labor; they should be counseled accordingly. The rate of labor induction is as high as 35% in women who have a body mass index (BMI) above 35.¹ Many of these inductions are indicated for maternal disease such as diabetes or preeclampsia. However, data suggest that obesity alone increases the induction rate, possibly through increased levels of leptin (an adipokine involved in obesity, appetite, and satiety), which may inhibit uterine contractions.²

Uterine and fetal monitoring

Monitoring of uterine contractions and fetal heart rate can be challenging in obese women. Early use of an intra uterine pressure catheter and fetal scalp electrode can help.

Shoulder dystocia

Obesity is a risk factor for macrosomia, which increases the likelihood of shoulder dystocia. In addition, at least one study supports maternal obesity as an independent risk factor for shoulder dystocia. Women who had a BMI above 30 were 2.7 times more likely to have a pregnancy complicated by shoulder dystocia, after adjustment for macrosomia, diabetes, parity, and induction of labor.³

Because of this risk, appropriate staff should be readily available for assistance, and operative vaginal delivery should be performed with caution, if at all.

Vaginal birth after cesarean delivery

Obese women who have a history of cesarean delivery need to be counseled about the higher risk of failed vaginal birth after cesarean (VBAC) and the likely need for repeat cesarean delivery. They also need to be told about the elevated risk of infection in the event that VBAC fails.

In women of normal weight, the likelihood of successful VBAC exceeds 80%, compared with a success rate of 68% for women who have a BMI above 29, and 60% for women who have a BMI above 40.^4,5

Appropriate counseling and patient selection are critical components of the decision to proceed with a trial of labor in obese women who have a history of cesarean delivery. Twenty-four-hour anesthesia and NICU coverage are also necessary in case emergent cesarean delivery becomes necessary.

Cesarean delivery

Morbidly obese women (BMI >35) have approximately a 50% greater chance of requiring cesarean delivery than do women of normal weight.⁶ The need for cesarean delivery rises with increasing BMI, probably because of a greater degree of maternal pelvic soft tissue, which increases the risk of both dystocia and cephalopelvic disproportion.

Anesthesia

It may be advisable to place an early epidural in laboring obese patients because they are more likely to require multiple placement attempts and cesarean delivery.

Intraoperative considerations

Ensure availability of the proper equipment

Table extenders, appropriate retractors, and long instruments should be readily available before surgery. For example, obstetricians often retract the panniculus to allow for a Pfannenstiel skin incision ( FIGURE 1 ), which works well to increase exposure. Moreover, the depth of the abdominal wall is much thinner beneath the panniculus.

However, be aware that, even in a supine patient with a leftward tilt, the weight of the panniculus can decrease vena caval return and cause uteroplacental insufficiency and compromised maternal respiration. Cesarean delivery should be performed expediently for these reasons.

A self-retaining elastic abdominal retractor may improve exposure at the same time that it minimizes the amount of retraction that must be exerted by the surgical assistant ( FIGURE 2 ).

FIGURE 1 Retract the panniculus

Retract the panniculus toward the patient’s head and use straps to secure it to facilitate a Pfannenstiel incision.

FIGURE 2 Elastic abdominal retractor improves visibility and access

Insert the inner ring of the adjustable elastic retractor into the abdominal cavity toward the patient’s head until it springs open against the parietal peritoneum. The outer ring is then rolled onto the plastic sleeve until it is snug against the skin.

 

Prophylaxis is warranted

Preoperative prophylactic antibiotics (weight-based) and prophylaxis for venous thromboembolism using sequential compression devices are recommended prior to surgery.

Choose the incision wisely

Data do not indicate whether vertical or transverse skin incisions for cesarean delivery are associated with higher infectious morbidity. In general, a Pfannenstiel incision is associated with less postoperative discomfort, allowing earlier mobilization and better respiratory function. A vertical incision allows optimal exposure, especially in the case of a macrosomic infant, and may thereby limit operating time and blood loss.^7,8

A vertical supraumbilical incision is another option. If the lower uterine segment is not accessible, a fundal uterine incision can be made ( FIGURE 3 ). The advantage of this method is increased exposure as well as access to the incision for wound care. However, because this method may necessitate a classical uterine incision, counseling must be given regarding future pregnancy.

FIGURE 3 Pair incisions strategically to ease cesarean delivery

In an obese patient, a supraumbilical skin incision paired with a classical uterine incision may simplify the surgery.

Other intraoperative considerations

If the surgery is prolonged, consider administering another dose of antibiotics.

If the subcutaneous tissue is thicker than 2 cm, it should be reapproximated to minimize the risk of hematoma and seroma formation and wound infection.^8,9

A subcutaneous drain should also be considered.

Postpartum care

Be aware of special risks

One retrospective study showed an increased risk of postpartum hemorrhage in women who had a BMI above 25, compared with women of normal weight. This risk increased as BMI increased. Knowledge of this complication and early use of uterotonic agents can minimize the morbidity associated with postpartum hemorrhage.

Postpartum infection is more likely in obese women, with three times the risk of endometritis of women of normal weight, and increased risks of wound infection, urinary tract infection, septic pelvic thrombophlebitis, and pneumonia.¹⁰ Early recognition of infection and administration of antibiotics can minimize morbidity.

Venous thromboembolism is more likely throughout pregnancy in obese women. Risk is heightened, however, during the postpartum period, when it is four times as high as the risk in women of normal weight.¹¹ Early ambulation and use of venous compression devices are encouraged. Consider heparin in the immediate postpartum period, when mobility is compromised for a longer period, particularly for women undergoing cesarean delivery who have comorbidities.

Suggest breastfeeding, weight loss

Women who breastfeed longer than 1 month have a 22% reduction in the risk of developing metabolic syndrome later in life, compared with women who do not. It also appears that a longer duration of breastfeeding reduces the risk of diabetes.¹²

Weight loss should be strongly encouraged. Women who retained their pregnancy weight at 6 months were 18 lb heavier after 10 years than women who lost their pregnancy weight.

The risk of metabolic syndrome increases with parity, probably because of the tendency of many obese women to retain their pregnancy weight.¹²

The authors report no financial relationships relevant to this article.

Hear Dr Phillips discuss the key points of this series

With the ranks of the obese expanding, and the severity of obesity increasing as well, obstetricians see a greater percentage of obese and morbidly obese gravidas in their practice. At the end of pregnancy, when it is time to deliver the infant, a number of issues must be taken into account to ensure the safety and health of both mother and child. Part 2 of this two-part article discusses these issues, from intrapartum and intraoperative considerations to care during the postpartum period.

Intrapartum concerns

Induction of labor

Obese women are more likely to require induction of labor; they should be counseled accordingly. The rate of labor induction is as high as 35% in women who have a body mass index (BMI) above 35.¹ Many of these inductions are indicated for maternal disease such as diabetes or preeclampsia. However, data suggest that obesity alone increases the induction rate, possibly through increased levels of leptin (an adipokine involved in obesity, appetite, and satiety), which may inhibit uterine contractions.²

Uterine and fetal monitoring

Monitoring of uterine contractions and fetal heart rate can be challenging in obese women. Early use of an intra uterine pressure catheter and fetal scalp electrode can help.

Shoulder dystocia

Obesity is a risk factor for macrosomia, which increases the likelihood of shoulder dystocia. In addition, at least one study supports maternal obesity as an independent risk factor for shoulder dystocia. Women who had a BMI above 30 were 2.7 times more likely to have a pregnancy complicated by shoulder dystocia, after adjustment for macrosomia, diabetes, parity, and induction of labor.³

Because of this risk, appropriate staff should be readily available for assistance, and operative vaginal delivery should be performed with caution, if at all.

Vaginal birth after cesarean delivery

Obese women who have a history of cesarean delivery need to be counseled about the higher risk of failed vaginal birth after cesarean (VBAC) and the likely need for repeat cesarean delivery. They also need to be told about the elevated risk of infection in the event that VBAC fails.

In women of normal weight, the likelihood of successful VBAC exceeds 80%, compared with a success rate of 68% for women who have a BMI above 29, and 60% for women who have a BMI above 40.^4,5

Appropriate counseling and patient selection are critical components of the decision to proceed with a trial of labor in obese women who have a history of cesarean delivery. Twenty-four-hour anesthesia and NICU coverage are also necessary in case emergent cesarean delivery becomes necessary.

Cesarean delivery

Morbidly obese women (BMI >35) have approximately a 50% greater chance of requiring cesarean delivery than do women of normal weight.⁶ The need for cesarean delivery rises with increasing BMI, probably because of a greater degree of maternal pelvic soft tissue, which increases the risk of both dystocia and cephalopelvic disproportion.

Anesthesia

It may be advisable to place an early epidural in laboring obese patients because they are more likely to require multiple placement attempts and cesarean delivery.

Intraoperative considerations

Ensure availability of the proper equipment

Table extenders, appropriate retractors, and long instruments should be readily available before surgery. For example, obstetricians often retract the panniculus to allow for a Pfannenstiel skin incision ( FIGURE 1 ), which works well to increase exposure. Moreover, the depth of the abdominal wall is much thinner beneath the panniculus.

However, be aware that, even in a supine patient with a leftward tilt, the weight of the panniculus can decrease vena caval return and cause uteroplacental insufficiency and compromised maternal respiration. Cesarean delivery should be performed expediently for these reasons.

A self-retaining elastic abdominal retractor may improve exposure at the same time that it minimizes the amount of retraction that must be exerted by the surgical assistant ( FIGURE 2 ).

FIGURE 1 Retract the panniculus

Retract the panniculus toward the patient’s head and use straps to secure it to facilitate a Pfannenstiel incision.

FIGURE 2 Elastic abdominal retractor improves visibility and access

Insert the inner ring of the adjustable elastic retractor into the abdominal cavity toward the patient’s head until it springs open against the parietal peritoneum. The outer ring is then rolled onto the plastic sleeve until it is snug against the skin.

 

Prophylaxis is warranted

Preoperative prophylactic antibiotics (weight-based) and prophylaxis for venous thromboembolism using sequential compression devices are recommended prior to surgery.

Choose the incision wisely

Data do not indicate whether vertical or transverse skin incisions for cesarean delivery are associated with higher infectious morbidity. In general, a Pfannenstiel incision is associated with less postoperative discomfort, allowing earlier mobilization and better respiratory function. A vertical incision allows optimal exposure, especially in the case of a macrosomic infant, and may thereby limit operating time and blood loss.^7,8

A vertical supraumbilical incision is another option. If the lower uterine segment is not accessible, a fundal uterine incision can be made ( FIGURE 3 ). The advantage of this method is increased exposure as well as access to the incision for wound care. However, because this method may necessitate a classical uterine incision, counseling must be given regarding future pregnancy.

FIGURE 3 Pair incisions strategically to ease cesarean delivery

In an obese patient, a supraumbilical skin incision paired with a classical uterine incision may simplify the surgery.

Other intraoperative considerations

If the surgery is prolonged, consider administering another dose of antibiotics.

If the subcutaneous tissue is thicker than 2 cm, it should be reapproximated to minimize the risk of hematoma and seroma formation and wound infection.^8,9

A subcutaneous drain should also be considered.

Postpartum care

Be aware of special risks

One retrospective study showed an increased risk of postpartum hemorrhage in women who had a BMI above 25, compared with women of normal weight. This risk increased as BMI increased. Knowledge of this complication and early use of uterotonic agents can minimize the morbidity associated with postpartum hemorrhage.

Postpartum infection is more likely in obese women, with three times the risk of endometritis of women of normal weight, and increased risks of wound infection, urinary tract infection, septic pelvic thrombophlebitis, and pneumonia.¹⁰ Early recognition of infection and administration of antibiotics can minimize morbidity.

Venous thromboembolism is more likely throughout pregnancy in obese women. Risk is heightened, however, during the postpartum period, when it is four times as high as the risk in women of normal weight.¹¹ Early ambulation and use of venous compression devices are encouraged. Consider heparin in the immediate postpartum period, when mobility is compromised for a longer period, particularly for women undergoing cesarean delivery who have comorbidities.

Suggest breastfeeding, weight loss

Women who breastfeed longer than 1 month have a 22% reduction in the risk of developing metabolic syndrome later in life, compared with women who do not. It also appears that a longer duration of breastfeeding reduces the risk of diabetes.¹²

Weight loss should be strongly encouraged. Women who retained their pregnancy weight at 6 months were 18 lb heavier after 10 years than women who lost their pregnancy weight.

The risk of metabolic syndrome increases with parity, probably because of the tendency of many obese women to retain their pregnancy weight.¹²

The authors report no financial relationships relevant to this article.

Hear Dr Phillips discuss the key points of this series

CASE: Obesity + coexisting conditions = complicated pregnancy and delivery

A 30-year-old gravida 8 para 5026 is referred from the clinic for evaluation of elevated blood pressure at 36 4/7 weeks’ gestation. She is morbidly obese, with a weight of 440 lb and a body mass index (BMI) of 67. She also has a history of chronic hypertension and was recently given a diagnosis of gestational diabetes, which has been controlled through diet.

Her reproductive history includes four full-term vaginal deliveries followed by cesarean delivery for malpresentation of twins. Her blood pressure is 180/100 mm Hg, and she has new-onset proteinuria (3+) and a headache. The diagnosis? Preeclampsia superimposed on chronic hypertension.

Induction of labor is initiated using a Foley bulb and oxytocin, and magnesium sulfate is given to prevent seizures. Over the next 48 hours there is minimal cervical change, and the patient develops chorioamnionitis, for which she is given intravenous antibiotics. A repeat cesarean delivery is performed via a Pfannenstiel skin incision. The surgery is uneventful, and the infant is healthy.

Are further complications likely?

Yes—additional complications are considerably more likely in this scenario than in one involving a patient of normal weight, especially given the patient’s chronic hypertension and gestational diabetes. Obesity can affect all aspects of pregnancy, from conception through the postpartum period, with the potential for significant adverse maternal and fetal outcomes, including maternal mortality.

As the number of obese women of reproductive age increases, obstetricians face new challenges in the management of complications during pregnancy, labor, delivery, and beyond. In Part 1 of this two-part article, we offer advice on how to counsel the obese patient about the very real risks she faces in pregnancy, and detail trimester-specific recommendations. In Part 2, which follows on page 51, we offer practical management strategies during intrapartum, intraoperative, and postpartum periods.

CASE CONTINUED

The patient becomes febrile and hypoxic on postoperative day 1. When a computed tomography scan fails to rule out pulmonary embolism, she is started on heparin.

On postoperative day 7, omentum is detected at the incision, and the patient is taken to the operating room, where fascial dehiscence is identified and necrotic tissue is debrided. Two days later, a wound vac and inferior vena cava filter are placed.

The patient is discharged to a rehabilitation center on postoperative day 22.

Management starts before conception

The most important strategy to prevent complications associated with obesity and pregnancy is prepregnancy weight loss. Ideally, all obese patients should have a prepregnancy consultation that includes the recommendation to lose weight before conception. At this consultation, the ObGyn should determine the patient’s BMI and risk category and advise her of the relevant maternal and fetal risks (page 51, we take up intrapartum and postpartum concerns.

The authors report no financial relationships relevant to this article.

Hear Dr Phillips discuss the key points of this series

CASE: Obesity + coexisting conditions = complicated pregnancy and delivery

A 30-year-old gravida 8 para 5026 is referred from the clinic for evaluation of elevated blood pressure at 36 4/7 weeks’ gestation. She is morbidly obese, with a weight of 440 lb and a body mass index (BMI) of 67. She also has a history of chronic hypertension and was recently given a diagnosis of gestational diabetes, which has been controlled through diet.

Her reproductive history includes four full-term vaginal deliveries followed by cesarean delivery for malpresentation of twins. Her blood pressure is 180/100 mm Hg, and she has new-onset proteinuria (3+) and a headache. The diagnosis? Preeclampsia superimposed on chronic hypertension.

Induction of labor is initiated using a Foley bulb and oxytocin, and magnesium sulfate is given to prevent seizures. Over the next 48 hours there is minimal cervical change, and the patient develops chorioamnionitis, for which she is given intravenous antibiotics. A repeat cesarean delivery is performed via a Pfannenstiel skin incision. The surgery is uneventful, and the infant is healthy.

Are further complications likely?

Yes—additional complications are considerably more likely in this scenario than in one involving a patient of normal weight, especially given the patient’s chronic hypertension and gestational diabetes. Obesity can affect all aspects of pregnancy, from conception through the postpartum period, with the potential for significant adverse maternal and fetal outcomes, including maternal mortality.

As the number of obese women of reproductive age increases, obstetricians face new challenges in the management of complications during pregnancy, labor, delivery, and beyond. In Part 1 of this two-part article, we offer advice on how to counsel the obese patient about the very real risks she faces in pregnancy, and detail trimester-specific recommendations. In Part 2, which follows on page 51, we offer practical management strategies during intrapartum, intraoperative, and postpartum periods.

CASE CONTINUED

The patient becomes febrile and hypoxic on postoperative day 1. When a computed tomography scan fails to rule out pulmonary embolism, she is started on heparin.

On postoperative day 7, omentum is detected at the incision, and the patient is taken to the operating room, where fascial dehiscence is identified and necrotic tissue is debrided. Two days later, a wound vac and inferior vena cava filter are placed.

The patient is discharged to a rehabilitation center on postoperative day 22.

Management starts before conception

The most important strategy to prevent complications associated with obesity and pregnancy is prepregnancy weight loss. Ideally, all obese patients should have a prepregnancy consultation that includes the recommendation to lose weight before conception. At this consultation, the ObGyn should determine the patient’s BMI and risk category and advise her of the relevant maternal and fetal risks (page 51, we take up intrapartum and postpartum concerns.

The authors report no financial relationships relevant to this article.

Hear Dr Phillips discuss the key points of this series

CASE: Obesity + coexisting conditions = complicated pregnancy and delivery

A 30-year-old gravida 8 para 5026 is referred from the clinic for evaluation of elevated blood pressure at 36 4/7 weeks’ gestation. She is morbidly obese, with a weight of 440 lb and a body mass index (BMI) of 67. She also has a history of chronic hypertension and was recently given a diagnosis of gestational diabetes, which has been controlled through diet.

Her reproductive history includes four full-term vaginal deliveries followed by cesarean delivery for malpresentation of twins. Her blood pressure is 180/100 mm Hg, and she has new-onset proteinuria (3+) and a headache. The diagnosis? Preeclampsia superimposed on chronic hypertension.

Induction of labor is initiated using a Foley bulb and oxytocin, and magnesium sulfate is given to prevent seizures. Over the next 48 hours there is minimal cervical change, and the patient develops chorioamnionitis, for which she is given intravenous antibiotics. A repeat cesarean delivery is performed via a Pfannenstiel skin incision. The surgery is uneventful, and the infant is healthy.

Are further complications likely?

Yes—additional complications are considerably more likely in this scenario than in one involving a patient of normal weight, especially given the patient’s chronic hypertension and gestational diabetes. Obesity can affect all aspects of pregnancy, from conception through the postpartum period, with the potential for significant adverse maternal and fetal outcomes, including maternal mortality.

As the number of obese women of reproductive age increases, obstetricians face new challenges in the management of complications during pregnancy, labor, delivery, and beyond. In Part 1 of this two-part article, we offer advice on how to counsel the obese patient about the very real risks she faces in pregnancy, and detail trimester-specific recommendations. In Part 2, which follows on page 51, we offer practical management strategies during intrapartum, intraoperative, and postpartum periods.

CASE CONTINUED

The patient becomes febrile and hypoxic on postoperative day 1. When a computed tomography scan fails to rule out pulmonary embolism, she is started on heparin.

On postoperative day 7, omentum is detected at the incision, and the patient is taken to the operating room, where fascial dehiscence is identified and necrotic tissue is debrided. Two days later, a wound vac and inferior vena cava filter are placed.

The patient is discharged to a rehabilitation center on postoperative day 22.

Management starts before conception

The most important strategy to prevent complications associated with obesity and pregnancy is prepregnancy weight loss. Ideally, all obese patients should have a prepregnancy consultation that includes the recommendation to lose weight before conception. At this consultation, the ObGyn should determine the patient’s BMI and risk category and advise her of the relevant maternal and fetal risks (page 51, we take up intrapartum and postpartum concerns.