Dutch investigators theorized that outcomes in new mothers would be better with initiation of plasma transfusion within 60 minutes of persistent postpartum hemorrhage (PPH). Findings from their new study, however, tell a different story.

 are from a multicenter cohort study conducted in the Netherlands. The authors identified women in the transfusion strategies in women during major obstetric hemorrhage (

) study, which retrospectively assessed transfusion strategies used in women during major obstetric hemorrhage. The cohort in the new analysis had persistent PPH, defined as PPH with at least 1000 mL of blood loss refractory to first-line interventions to control bleeding.

In the Netherlands, in women with PPH who are hemodynamically stable enough, uterine or internal iliac artery embolization is used before resorting to hysterectomy. If embolization is not available in an institution, it is common practice to transfer the patient to a nearby hospital with embolization facilities.

The current study included 1216 women (mean age 31.6 years) with PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. The authors used time-dependent propensity score matching to select women who received plasma during the first 60 minutes of persistent PPH. Each woman was matched with a woman who had PPH of the same severity and received the same treatment but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests.

The main outcomes were incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization. Seven of the women (0.6%) died of PPH, 62 (5.1%) underwent hysterectomy, and 159 (13.1%) had uterine artery embolization.


	Among women who received plasma during the first 60 minutes of persistent PPH, 114 could be matched with a comparable woman who had not received plasma at the moment of matching. Incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio 1.09; 95% CI 0.57-2.09).  Results of sensitivity analyses were comparable to the primary results.


	While the results do not support the authors’ original hypothesis, they said they should not be taken to indicate that plasma transfusion has no place in treatment of women with severe PPH. “Rather,” they said, “our study underlines the importance of developing tools to diagnose coagulopathy during persistent PPH. These tools may enable individualization of treatment of women with persistent PPH by identifying women who develop coagulopathy during persistent PPH.”

Articles

Published in JAMA Network Open, a new study offers surprising results about plasma transfusion effectiveness for women with PPH.

Plasma transfusion for persistent postpartum hemorrhage: Does timing matter?

A nationwide study by Swedish researchers suggests that inducing labor at no later than 41 weeks could be one of the few interventions that reduce stillbirths. While urging caution in interpretation of their results, the authors say the findings could be particularly important for management of nulliparas.

-which was stopped early because of a significantly higher rate of perinatal mortality in the expectant management group-were published in 

) was a multicenter, open-label, randomized superiority trial conducted at 14 hospitals in Sweden from 2016 to 2018.


	Of the 2760 women enrolled, all of whom had low-risk, uncomplicated pregnancies, 1381 were randomized to induction at 41 weeks and 1379 to expectant management with induction at 42 weeks. In many centers in the UK and Scandinavia, induction is common no later than 42 weeks. Recent studies have shown a significantly increased risk of perinatal mortality and morbidity at 41 weeks, and of stillbirth beginning at 39 weeks.

The primary outcome of SWEPIS was a composite of perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar < 7 at 5 minutes, pH < 7.00 or metabolic acidosis in the umbilical artery, hypoxic ischemic encephalopathy, intracranial hemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, or obstetric brachial injury. The secondary outcome was perinatal mortality. The primary analysis was intent to treat.


	No perinatal deaths occurred in the group induced at 41 weeks but six occurred in the expectant management group (5 stillbirths, 1 early neonatal death; 

 = 0.03). No differences were seen between the groups in the composite primary perinatal outcome (2.4% [33/1381] induction group; 2.2% [31/1379] expectant management; RR 1.06, 95% CI 0.6 to 1.73; 

 = 0.90). The proportion of cesarean deliveries, instrumental vaginal deliveries, or major maternal morbidities also did not differ between the groups.

The authors also found that in the induction group, there were fewer admissions to a neonatal intensive care unit, lower incidence of neonatal jaundice requiring therapy, and fewer infants with macrosomia. The rate of cesarean delivery did not differ significantly between the two groups.

Of note, the researchers said, all perinatal deaths occurred in the nulliparous women. “If this finding can be replicated in future studies,” they indicated,” it could mean that nulliparous women may require particular attention, and interventions such as labor induction might be even more important in this group.” The number needed to treat with induction of labor at 41 weeks to prevent one perinatal death was 230, which the authors said was lower than previous estimates.

A study published in BMJ suggests that inducing labor at no later than 41 weeks could be one of the few interventions that reduce stillbirths.

Induction of labor and risk of stillbirth

Vulvovaginal candidiasis (VVC) is relatively common, and published 

indicates a woman’s risk of it could be increased by certain personal behaviors as well as the composition of her vaginal microbiota. 

is the most common etiology for VCC and this study looked at what factors are associated with its molecular detection. The objective of the study was to better understand epidemiologic factors associated with molecular 

detection and to evaluate how the vaginal microbiota and relative abundance of individual bacterial taxa differ between women with and without 


	For the cross-sectional study, vaginal swabs were self-collected by 394 nonpregnant, reproductive-age women. The participants submitted two swabs; one was used to characterize the composition and structure of the vaginal microbiota and the other was used the prepare a smear for Nugent Gram stain scoring. 

using polymerase chain reaction targeting 

ITS1/2 region. Vaginal microbiota was characterized using 16S rRNA gene amplification sequencing of the V3 to V4 hypervariable regions and then clustered into community state types (CSTs). 

Five primary CSTs were identified in this study; four dominated by 

L. iners, L. crispatus, L. gasseri, L. jensenii

), plus one lacking significant numbers of 

and characterized by higher proportions of strict and facultative anaerobic bacteria (termed CST IV).The authors used multiple logistic regression to identify risk factors associated with 

in in 21% of vaginal samples (83 of 394). Women in whom 

was detected were more likely to report use of tampons, engage in receptive oral sex, and use of over-the-counter (OTC) antifungals to self-treat for vaginal infections before seeing a doctor for examination. 

Neither self-reported diagnosis of VVC nor bacterial vaginosis in the prior 60 days were associated with 

detection. Furthermore, detection was not associated with vaginal pH, reporting any type of vaginal symptom in the past 60 days, age, history of pregnancy, use of hormonal contraception in the past 60 days, number of recent sexual partners, or other forms of sexual activity in the past 60 days. 

In multivariable modeling, women with a 

-dominated CST had increased, but not statistically significant, odds  of 

CST IV after cofactor adjustment of receptive oral sex and a history of self-treatment with OTC antifungals (adjusted odds ratio, 2.05%; 95% CI 0.97-4.37, n=323). However, using the same model, antifungal use and receptive oral sex were significantly associated with 

detection, with a dose-response trend for increasing frequency of oral sex and escalating odds of 

When assessing individual bacteria to determine if there were taxa that were most likely to be associated with 

L. crispatus, Lactobacillus coleohominis, Prevotella oris, 

as being in higher relative abundance in women in whom 


	The authors believe their findings indicate that 

-dominated vaginal microbiota may be associated with increased 

detection. They also point to receptive oral sex as a risk factor for 

colonization. Further studies are recommended, and the authors suggest focusing on what roles the vaginal microbiota and host immune response play in the transition from asymptomatic colonization to symptomatic VCC.

Published research from Sexually Transmitted Diseases indicates a woman’s risk of vulvovaginal candidiasis could be increased by certain personal behaviors as well as the composition of her vaginal microbiota.

Microbiota composition, receptive oral sex may be risk factors for candidiasis

Postoperative complications from laparoscopic treatment for suspected endometriosis could not be predicted by preoperative patient characteristics or surgical findings of advanced endometriosis, according to a retrospective cohort 

Acta Obstetricia et Gynecologica Scandinavica

 did find that adhesiolysis, ureterolysis and an increased number of total procedures were predictive of perioperative complications.

“Laparoscopic treatment of endometriosis is highly variable, depending on the goals of the patient, the extent of disease and the skills of the surgeon,” said principal investigator 

, a minimally invasive gynecologic surgeon at 

 in Boston. “For instance, a simple procedure may only require a laparoscopic survey and a peritoneal biopsy, whereas a more complex procedure may entail a radical excision of all deep-infiltrating lesions, paralleling an oncologic debulk.”

Dr. Clark pointed out that it would be helpful to understand what factors increase surgical complexity and increase a patient’s risk of a complication. “We undertook this study in hopes of identifying preoperative or intraoperative factors that would predict a complication,” she told 


	The cohort of 397 women underwent laparoscopic treatment of suspected endometriosis at 

 in Boston between 2009 and 2016. Predictors of major perioperative complications were assessed by comparing the characteristics of women who had any major intraoperative or postoperative complications to women who had no complications.

The procedures were excision of superficial endometriosis (55.4% of women), excision of deepâinfiltrating endometriosis (24.9%), fulguration of endometriosis (38.3%), hysterectomy (23.2%), ovarian cystectomy (35.5%), salpingectomy (18.6%), oophorectomy (15.1%) and bowel resection (1.0%). The women, many of whom had multiple procedures, were followed for 60 days following each surgery, during which time 4.5% (n = 18) developed a major perioperative complication.


	Women with advanced endometriosis (defined as stage III or IV endometriosis, rectovaginal endometriosis or deep-infiltrating endometriosis) were more likely to have a complication, though not a statistical significant difference. In total, 77.8% of women with a complication versus 56.7% of women without a complication had advanced endometriosis (

On the other hand, women with a complication were significantly more likely to have undergone adhesiolysis or ureterolysis: 88.9% with a complication versus 52.5% without a complication for adhesiolysis (

 = 0.002) and 61.1% of women with a complication versus 28.8% without a complication for ureterolysis (

 = 0.003). The total number of procedures was also greater for women who had a complication: 4.3 vs. 3.2 (

 = 0.003). All other procedure characteristics were comparable between women with and without complications.


	“We were surprised to find that advanced endometriosis did not increase the risk of a complication with statistical significance,” Dr. Clark said. “Instead, we found that certain intraoperative procedures, such as ureterolysis and adhesiolysis, and the total number of procedures performed increased the risk of a complication.”

These procedural factors are surrogates for surgical complexity that more reliably predict complications than disease classification, according to the study. “Our study suggests that intraoperative events are the main driver of postoperative surgical outcomes,” Dr. Clark said. “One could conclude, therefore, that patients who undergo extensive laparoscopic dissection are most at risk of a complication, and thus surgeons should have heightened awareness for potential complications during or after surgery in these women.”

However, because the study did not find any preoperative patient characteristics that predicted a complication, “this limits the ability to apply these findings to patient counseling prior to surgery,” she said.

Future improvements in radiologic imaging, like assessment for deep-infiltrating disease with pelvic ultrasound and magnetic resonance imaging (MRI), “will hopefully improve our ability to identify patients at risk of requiring significant dissection and its associated risks,” he said.

Dr. Clark reports no relevant financial disclosures.

Although patient characteristics may not able to predict postoperative complications from laparoscopic treatment, procedural factors appear to be predictive of perioperative complications.

Predictors of complications for laparoscopic treatment of endometriosis

Both natural and surgical premature menopause before age 40 are associated with a small but statistically significant increased risk for subsequent cardiovascular disease (CVD) compared to that in postmenopausal women without premature menopause, according to a cohort 

The composite outcome included coronary artery disease, heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation, ischemic stroke, peripheral artery disease and venous thromboembolism.

The authors noted that although recent guidelines embrace using history of menopause before age 40 to refine atherosclerotic cardiovascular disease (ASCVD) risk assessments in middle-aged women, “robust data on cardiovascular disease risk in this population is lacking.”


	The cohort of 144,260 eligible women was from the large-scale, long-term observational 

, comprising adult residents of the United Kingdom recruited between 2006 and 2010. All included women were 40 to 69 years old (mean age 59.9) and postmenopausal at study enrollment, with median follow-up of 7 years through August 2016. Natural premature menopause was defined as menopause before age 40 without oophorectomy, while surgical premature menopause was bilateral oophorectomy before age 40.


	Overall, 3.4% (n = 4,903) of women had natural premature menopause and 0.4% (n = 644) had surgical premature menopause. The primary outcome of incidence of composite CVD was 3.9% (n = 5,415) in women with no premature menopause (5.7/1,000 woman-years) and 6.0% (n = 292) in women with natural premature menopause (8.78/1,000 woman-years), representing a difference vs. no premature menopause of +3.08/1,000 woman-years (95% confidence interval [CI]: 2.06 to 4.10; 

Among the 7.6% of women (n = 49) with surgical premature menopause (11.27/1,000 woman-years), the difference vs. no premature menopause was +5.57/1,000 woman-years (95% CI: 2.41 to 8.73; 

 < 0.001). Overall, natural and surgical premature menopause had hazard ratios of 1.36 (95% CI: 1.19 to 1.56; 

 < 0.001) and 1.87 (95% CI: 1.36 to 2.58; 

< 0.001), respectively, after accounting for conventional CVD risk factors and menopausal hormone therapy.

“These results may have implications for understanding and mitigating the long-term risk for cardiovascular disease associated with premature menopause,” wrote the authors from Massachusetts, Connecticut and Florida. For instance, history of premature menopause allows for primordial prevention, which is a targeted nonpharmacologic strategy to reduce the risk of developing cardiovascular risk factors.

 found that a higher premenopausal Framingham risk factor was linked to earlier age at menopause. The current study, though, concluded that premature menopause may not be limited to comorbid with conventional CVD risk factors, but may separately increase odds of developing these risk factors. In addition, the study found that the CVD risk connected to premature menopause extended beyond ASCVD.


	“Postmenopausal state is associated with increase in cytokines and oxidative stress, which may contribute to osteogenesis of valvular interstitial cells,” wrote the authors, noting that it is unknown if this mechanism links premature menopause to aortic stenosis.

Lastly, the form of menopause may be connected to differential cardiovascular risk. Although significant differences in risk between natural and surgical premature menopause were not evident in fully adjusted models, risk differences may arise from differential development of conventional cardiovascular risk facts. There is also the possibility the study had reduced statistical power.

The authors said further research is needed to understand the mechanisms causing the associations between premature menopause and CVD.

Women who reach menopause before age 40 may have an increased risk for subsequent cardiovascular disease, according to research from JAMA.

Premature menopause and cardiovascular disease

’s founding Editor-in-Chief, Dr. John Queenan, to join its Editorial Board. It was an unexpected honor and just a bit intimidating given that the Board was a veritable “who’s who” of ob/gyn greats.  I quickly realized that the twin pillars of the magazine’s success were John’s inspirational leadership and the quality, sagacity, and editorial independence of that board. For 25 years, Dr. Queenan had been a master at picking the 

 board members who, in turn, identified key topics, emerging trends and outstanding authors. John led their deliberations, added his own prescient ideas and, of course, crafted truly memorable editorials.

The next year, I was stunned when John asked me to become 

’s second Editor-in-Chief. I have enjoyed my time in this post immensely. Fortunately, I strictly followed John’s “recipe” by assembling a great board, a number of whom have been with me since the start, including Drs. Joe Leigh Simpson, Paula Adams Hillard, and Sharon Phelan. I was blessed to be able to add other leaders in the field including my old friends Joshua Copel from Yale, one of the true greats in obstetrical ultrasound, and Sarah Kilpatrick, Chair of Obstetrics and Gynecology at Cedars-Sinai in Los Angeles and an expert in medical complications of pregnancy. Newer friends joined including Drs. John Delancey, a pioneer and leader in urogynecology; Ilana Cass, a brilliant gynecologic oncologist and now Chair of the Department  of Obstetrics & Gynecology at Dartmouth; Chris Pettker, a leader in the patient safety movement from Yale; and Steve Ory, a master clinician and reproductive endocrinologist from Florida International University in Miami. I was also lucky enough to recruit Dr. Jon Einarsson, an international authority in minimally invasive gynecological surgery from Harvard, as Deputy Editor. What great success the magazine has enjoyed over the past two decades is largely due to these wonderful folks as well as their predecessors, including giants like Drs. Leon Speroff and Ed Wallach. 

Perhaps the most daunting task over the past two decades has been coming up with ideas for editorials. Some concepts were obvious, like telling the story of 9/11 from the perspective of my patients at NYU and Bellevue Hospital. Others were inspired by the recurrent professional liability crisis, onerous new government regulations, political threats to women’s reproductive health, rapidly changing healthcare financing, physician burnout, and the challenges of residency training. However, most reflected bread and butter clinical topics including the safety of vaginal breech deliveries and trials of labor after prior cesareans, the causes of maternal mortality and preterm birth, the appropriate use of antenatal corticosteroids, misoprostol and low molecular weight heparin, and screening for thrombophilias, genetic disorders, Group B 

 and gestational diabetes. Gyn topics included postmenopausal hormone therapy, new contraceptives, screening for cervical cancer, and the need to encourage human papillomavirus vaccination. While I have not shied away from controversial topics, I have also tried to tell stories from the perspective of busy clinicians. 

Click here to read some of Dr. Lockwood's editorials

And I have been honored to receive a number of national publishing awards for these editorials, including three prestigious Jesse H. Neal Awards from the American Society of Business Publication Editors, as well as two Gold Awards for Editorials and an Award in the Editorial/Editor’s Letter category from the American Society of Healthcare Publication Editors. My approach to writing has been simple: find a topic I was interested in or passionate about, critically review all relevant literature, and then sit down and write. I do hope my editorials have helped shape ob/gyn practice in positive ways. I have certainly enjoyed hearing from readers, who have not been shy about providing feedback in person, by phone, by e-mails, through formal letters to the editor, and more recently, via social media.  

It is hard to imagine it’s been 20 years. I have truly enjoyed every minute. But this seems like a propitious time to pass the Editor-in-Chief “baton” to someone from the next generation of ob/gyn leaders who can provide a different perspective and their own passion. Over the next few months, the magazine will select a new leader and I am sure they can maintain 

’s extraordinary success over the past 45 years if they also follow John Queenan’s tried and true formula. 

In closing, I want to thank our dedicated, brilliant, and very witty past and present editorial board members. I am also incredibly grateful to my terrific managing editors, including Judy Orvos, Paul Cerrato, Susan Olmstead, and Linda Wetzel, whose professionalism and sage counsel have been invaluable. Finally, I want to thank our wonderful readers, who were my inspiration.

After 20 years as editor-in-chief, Dr. Lockwood announces that he has stepped down and reflects on his time with the magazine.

A fond farewell

A 32-year-old G5P4004 with four prior cesarean deliveries underwent an ultrasound at 12 weeks’ gestation, which revealed a pregnancy in the lower uterine segment with a probable placenta previa. An ultrasound at 20 weeks’ gestation revealed a definite placenta previa, with lacunae and hypervascularity suggestive of a morbidly adherent placenta (MAP, now called placenta accreta spectrum). Magnetic resonance imaging (MRI) confirmed the ultrasound findings. 

Although the mother was a long-term patient of the obstetrician, she was transferred from a community setting to a regional perinatal center 40 miles away. Her care continued at the perinatal center with a plan for cesarean hysterectomy at 34 to 35 weeks’ gestation. The patient was instructed to call the perinatal center immediately if she experienced any bleeding or significant contractions prior to the planned delivery date.

At 32 weeks’ gestation, the patient awoke in the night with severe pain and bleeding. She called 911 and was brought by ambulance to the local community hospital at 11:00 pm, where, fortuitously, the original referring physician was on call. Although the physician had not cared for the patient for several months, regular communication had been from the perinatal center. The physician was aware of the plan for cesarean hysterectomy. Although the patient’s vital signs and fetal heart monitor readings were stable, the degree of pain and bleeding necessitated urgent delivery at the community hospital. Anesthesia was consulted, multiple sites of intravenous (IV) access were established, and the blood bank was prepared for possible massive hemorrhage. The patient underwent a low transverse cesarean under general anesthesia and delivered a viable male infant who weighed 1845 g and had Apgar scores of 5 and 7 at 1 and 5 minutes, respectively. The baby did well. The placenta separated “normally,” but significant bleeding was noted at delivery and the estimated blood loss was not documented. Although bleeding initially was brisk, the uterus was deemed “dry” following primary closure. 

Over the next 6 hours, the patient had multiple episodes of hypotension and bleeding. She did not leave the operating room (OR), nor could she be extubated. She received multiple uterotonics, 12 units of packed red blood cells and 10 units of fresh frozen plasma. The community obstetrician consulted with the regional perinatal center, as well as intensivists and hematologists at the community hospital. Subsequently, the patient developed disseminated intravascular coagulation (DIC). She was ultimately transported by helicopter to the regional perinatal center, where she was moribund on arrival and died upon admission to the hospital. Autopsy concluded that death was due to the obstetrical hemorrhage and DIC from a placenta accreta. 

The patient’s family sued for wrongful death of the woman. They sued the community physician for: 

Not offering pregnancy termination at 12 weeks’ gestation, when the placenta accreta first was suspected; 

Not referring the patient to the perinatal center until after 20 weeks, after the time when termination would have been available;

Not transferring the patient to the regional perinatal center after initial stabilization on the night of delivery; 

Not executing the delivery plan, specifically performing a cesarean hysterectomy at the time of delivery; and 

Not reopening the patient while in the OR to perform a life-saving hysterectomy. 

The family also sued the perinatal center for not admitting the patient at 30 to 32 weeks for in-patient observation. They also sued the perinatal center for not recommending a hysterectomy during consultation shortly after delivery, while the patient was in the OR. 

The community physician stated that the patient was happy with the pregnancy and termination was never an issue. Upon admission she was not stable enough for transfer. The cesarean was performed in a timely manner, with delivery of a healthy infant who required only a short stay in the Level II nursery. Further, despite the diagnosis of MAP, the placenta delivered easily, and thus, a cesarean hysterectomy, with its increased morbidity, was not necessary. None of the consultants recommended further surgery. The anesthesiologists opined that the patient was not stable enough for further surgery, throughout the 6 hours that she remained in the OR. Everything possible was done and, despite that, the patient succumbed.

The perinatal center physicians stated it was not the standard of care to admit patients with MAP prophylactically at 30 to 32 weeks’ gestation. Further, although they recommended earlier transfer and hysterectomy, the community physician felt the patient was too unstable for either further surgery or transfer. 

Prior to trial, a large settlement was made on behalf of the community obstetrician. The perinatal center was dismissed from the claim. 

Risk factors for MAP (placenta accreta spectrum) include previous cesarean delivery, with likelihood increasing from 0.3% for one previous cesarean delivery to 6.74% for five or more cesarean deliveries. Placenta previa further increases risk for MAP. Ultrasound remains the mainstay of diagnosis, although there exists significant interobserver variation. In this case, the diagnosis was made by the community physician, confirmed with MRI, with appropriate referral to a higher level of maternal care-the regional perinatal center-although not early enough for pregnancy termination to be considered. For previa pregnancies, counseling for pregnancy termination for material indications should be documented. In this case, the planned timing and location of delivery comported with recommended management.

Regional perinatal centers have multidisciplinary teams, which may include MFM specialists, gynecologic oncology, urology, vascular surgery, trauma surgery, interventional radiology, hematology, intensivists, and a fully functional blood bank with extensive resources. Further, these centers have substantial support services and staff, including more extensively trained nursing staff and OR personnel. This environment enhances favorable outcomes.

This community obstetrician was clearly placed in a difficult situation, which occurs when delivery plans are disrupted by clinical circumstances. The obstetrician could have considered asking for surgical assistance from a general surgeon, trauma surgeon, urologist, or even surgical oncologist. Because the patient was not stable enough for transfer, proceeding with the cesarean delivery was appropriate. Several management options were available following the delivery, including leaving the placenta attached, with subsequent methotrexate, or removing the placenta and using prophylactic or therapeutic tranexamic acid, insertion of a Bakri balloon, or uterine artery embolization. The obstetrician also could have left the placenta attached, closed the uterus, and proceeded with hysterectomy. Alternatively, assuming the patient was stable after leaving the placenta attached, transfer to the regional perinatal center for further care could have been considered. 

In cases refractory to uterotonics, massage, and tamponade, hysterectomy is recommended. Unfortunately, the delay in responding to the ongoing bleeding, e.g. not proceeding with hysterectomy in a prompt fashion, contributed to the patient’s demise. Although the ultimate result may have been unchanged, proceeding with the hysterectomy in a timely manner would have enhanced defensibility in this case.

Dr. Shwayder is extremely grateful to Steven Warsof, MD, who shared this case from his files. The case also appears in a book they coauthored,

Legal Concepts and Best Practices in Obstetrics: The Nuts and Bolts Guide to Mitigating Risk

Did this community physician act accordingly after the patient was diagnosed with MAP?

Disrupted delivery plan leaves OB in difficult situation

Initiating a highly effective method of contraception in the immediate postpartum period has several benefits, including assurance that the woman is not pregnant and avoidance of short interpregnancy intervals. Between 40% and 57% of women report having unprotected intercourse before the routine 6-week postpartum visit and ovulation occurs as early as 25 days, putting postpartum women at risk of unintended pregnancy.

 Several experts have recommended moving the postpartum visit to 2 weeks instead of 6 weeks because of the high risk of unintended pregnancy. Recently, the American College of Obstetricians and Gynecologists (ACOG) has recommended that women have some contact with their obstetrical provider within the first  3 weeks postpartum.

 However, awaiting the postpartum visit to initiate effective contraception can be problematic as approximately 10% to 40% of women do not attend this visit.

In the first year postpartum, 70% of pregnancies are unintended.

 Unintended and short-interval pregnancies are associated with increased rates of preterm birth and adverse maternal and neonatal outcomes.

 The World Health Organization recommends spacing pregnancies at least 18 months apart and in the United States, the Office of Disease Prevention and Health Promotion continues to aim to reduce the proportion of pregnancies conceived within 18 months of a previous birth, per their Healthy People 2020 objectives.


	Intrauterine devices (IUDs) and contraceptive implants, also known as long-acting reversible contraceptives (LARC), are the most effective reversible contraceptives and can be safely initiated immediately postpartum. LARCs have the highest continuation rates among reversible methods with effectiveness greater than 99% (Figure 1). The major advantages of LARCs are that they are not user-dependent and return to fertility is rapid after discontinuation. Placement in the postpartum period is associated with higher continuation rates compared with interval placement. ACOG supports immediate postpartum LARC insertion as a best practice.

LARC methods available in the United States

Currently there are five IUDs and one contraceptive implant available in the United States. 


	Paragard is the copper T380A IUD commercially available in the United States.  It is US Food and Drug Administration-approved for use up to 10 years but has been shown to be effective up to 12 years.

 The T-shaped device is a base of polyethylene wrapped with copper wire around the stem and arms.  Mechanisms of action (MOAs) include inhibition of sperm migration and viability and damage to or destruction of the ovum.

 Postfertilization events may occur, but the copper IUD does not disrupt a pregnancy after implantation. It has a reported 1-year failure rate of 0.8 per 100 women. The most-reported adverse events (AE) are abnormal uterine bleeding and pain.


	There are four levonogestrel intrauterine systems (LNG-IUS) currently available in the United States (Mirena, Liletta, Kyleena, Skyla) (Table 1). All are T-shaped and include a polydimethylsiloxane sleeve containing levonorgestrel in the stem. All LNG-IUS have a similar primary MOA: prevention of fertilization by increasing the amount and viscosity of cervical mucus.

 Most women who use an LNG-IUS ovulate but experience diminished menstrual bleeding due to the local effect of the levonorgestrel on the endometrium.

 LNG-IUS are not abortifacients and do not disrupt pregnancy.  


	The etonogestrel contraceptive implant is placed subdermally and consists of an ethylene vinyl acetate copolymer core containing 68 mg of etonogestrel. The single-rod implant is 4 cm in length and 2 mm in diameter and is preloaded in a disposable sterile applicator. The 2001 version of the implant has been updated and was introduced to the United States in 2011.

 The newer implant is radio-opaque with a new inserter designed to prevent deep placement. Its primary MOA is ovulation suppression, but it also thickens cervical mucus and has endometrial effects.

 After implant insertion, changes in menstrual patterns are common and include amenorrhea, or frequent, infrequent, or prolonged bleeding.  Complications related to implant insertion and removal are rare. 


	ACOG states that immediate postpartum IUD insertion (within 10 minutes after placental delivery in vaginal and cesarean births), should be offered routinely as a safe and effective option for postpartum contraception.

 The Centers for Disease Control and Prevention US Medical Eligibility Criteria (US CDC MEC) classifies immediate postpartum copper IUD insertion as Category 1 (Table 2).  Immediate postpartum insertion of LNG-IUS and the contraceptive implant is MEC Category 1 or 2, depending on breastfeeding status (Table 2). Immediate postpartum IUD insertion is contraindicated for women in whom uterine infection, puerperal sepsis, or ongoing postpartum hemorrhage are diagnosed. Immediate postpartum initiation of the contraceptive implant either before hospital discharge or after a hospital stay for birth should be offered routinely as a safe and effective options regardless of breastfeeding status. The US CDC MEC classifies placement of an implant in non-breastfeeding women less than 21 days postpartum as Category 1 and classifies placement for breastfeeding women as Category 2, given theoretical concerns regarding milk production; after 30 days postpartum, it is classified as US MEC Category 1 in breastfeeding women.

Postplacental IUD perforation and expulsion 


	Uterine perforation at time of postplacental IUD placement is rare. In a prospective study of 8343 women receiving the Copper T380A at different postpartum timings, only one perforation occurred out of 460 postplacental insertions (0.2%).

 This risk is not greater than with interval IUD insertion.

The rate of postplacental IUD expulsion, on the other hand, is higher than after interval insertion. Reported expulsion rates range from 2% to 27% after vaginal delivery and 0% to 20% after cesarean delivery.

 In a large randomized controlled trial (RCT) of postplacental IUD insertion, Chen et al. randomized 102 women to postplacental insertion of the 52-mg LNG-IUS or interval insertion 6 to 8 weeks later. Expulsion was higher with postplacental insertion than with interval insertion. However, 10 of 12 women who experienced expulsion after immediate postpartum placement had a new LNG-IUS inserted and both groups had similar rates of IUS use at 6 months (84% vs. 77%, 

Another study randomized women to immediate IUD placement at cesarean delivery versus interval placement at
	6 weeks postpartum and found that significantly more women in the immediate placement group continued the IUD at 6 months (83% vs. 64%, RR 1.3, CI 1.02-1.66).

 In the interval group, 39% did not obtain the IUD, 25% did not return for the postpartum visit, and 14% either declined the IUD or had an unsuccessful insertion.

 When looking at expulsion rates after postplacental IUD insertion versus after insertions at other postpartum intervals (> 10 min to 48 or 72 hours), data are conflicting. Despite the higher expulsion rate for immediate postpartum IUD placement, evidence from clinical trials and cost-benefit analyses strongly suggest superiority of immediate placement, especially for women at greatest risk of not having recommended postpartum follow-up. Patients should be counseled about the increased expulsion risk, as well as signs and symptoms of expulsion. Given that many women experience barriers to interval LARC placement, advantages of immediate postpartum placement may outweigh disadvantages.


	Postplacental IUD insertion does not appear to cause increased vaginal bleeding.  A Cochrane review of RCTs comparing immediate postpartum versus delayed insertion of the contraceptive implant found that women who received an immediate postpartum implant had a higher mean number of days of abnormal vaginal bleeding and side effects within 6 weeks postpartum but that did not lead to differences in continuation rates at 6 months.

 There appeared to be little or no difference between the groups in heavy irregular vaginal bleeding or associated severe cramping within 12 months. 


	Given that progesterone withdrawal after delivery of the placenta is thought to trigger lactogenesis, there are theoretical concerns about progestin IUDs and implants preventing onset of milk production. Observational studies suggest they have no effect on lactogenesis, successful initiation and continuation of breastfeeding, or on infant growth and development. The Copper-T lacks hormones and thus is classified MEC Category 1 for immediate postpartum use by breastfeeding women. Data on the immediate postpartum use of LNG-IUS are limited to a secondary analysis of a small RCT of immediate versus delayed postpartum placement, which showed no difference in patient-reported breastfeeding at 6 to 8 weeks and 3 months. However, more women in the delayed placement group reported breastfeeding at 6 months.

 Small numbers limit the ability to draw definitive conclusions from this study. 

Given current available evidence, women should be counseled about theoretical risks of reduced duration of breastfeeding with immediate LNG-IUS placement but the majority of evidence has not shown a negative effect on breastfeeding outcomes.

 For this reason, immediate postpartum insertion of an LNG-IUS in breastfeeding women is classified as MEC Category 2.

 Placement of the contraceptive implant in non-breastfeeding women less than 21 days postpartum is Category 1 and placement for breastfeeding women is Category 2; after 30 days postpartum, it is Category 1 in breastfeeding women.


	One of the main considerations for postpartum contraception is risk of venous thromboembolism (VTE), given the already increased risk in this period. The Copper T, LNG-IUS, and implant do not increase risk of VTE and are good options for women with medical problems for which estrogen is contraindicated.


	After vaginal delivery, IUD insertion can be performed manually or with a ring forceps.  The IUD is removed from the inserter and strings are trimmed to 10 cm. Typically, the strings of the Copper T do not need to be trimmed. The arms of the IUD are gently grasped with the forceps and placed at a slight angle to facilitate placement. The IUD is passed through the cervix to the fundus with the other hand applying downward fundal pressure. Ultrasound guidance can be used to ensure appropriate positioning. At time of cesarean delivery, after delivery of the placenta and uterine tone is achieved, the IUD is placed at the fundus with the inserter, manually or with the ring forceps, and the strings are directed through the cervix. The hysterotomy is then closed in the usual fashion. Formalized training is advisable prior to provision of an immediate postpartum IUD; ACOG instructional videos are available.

Currently there is insufficient evidence to support routine use of ultrasound for postplacental placement of IUDs, so it is reasonable not to use the technology this setting. If there is a concern about fundal placement of the IUD, an ultrasound can be used to ensure proper positioning. Lack of ultrasound availability should not prohibit provision of postplacental IUD at time of vaginal delivery.


	ACOG now recommends that, ideally, all women have some contact with an obstetrical provider within the first 3 weeks postpartum; the timing of a comprehensive postpartum visit should be individualized and patient centered.

 Assessment of how a patient is doing with her immediate postpartum LARC should be performed. For patients who have had postplacental IUD placement, a speculum exam can be performed to visualize the IUD strings. The strings can be trimmed as they often lengthen. Routine ultrasound surveillance is not recommended. 

If incidental displacement of the IUD is diagnosed, removal is not mandated but can be considered after appropriate patient counseling, if desired.

 Patients who receive a postpartum implant should be examined like any other patients with an implant, with verification that the device can be palpated and inspection of insertion site.


	Inability to visualize IUD strings after postplacental placement ranges from 5% for LNG-IUS placement after vaginal delivery to 44% to 79% for IUD placement during cesarean delivery.

 If the IUD strings are not visualized or palpated at the external os, it may be necessary to use ultrasound to confirm the intrauterine location. Women who undergo postplacental IUD placement should be counseled that confirmation of the IUD may require ultrasound examination.


	Several studies have shown that postpartum insertion of LARC typically is more expensive up front but is cost-saving overall because of reductions in future unintended pregnancies. A 2015 cost-effectiveness analysis calculated postpartum IUD placement had an estimated cost savings of approximately $282,540 per 1,000 women over a 2-year period. Higher cost was incurred at time of postplacental IUD placement due to more devices used (in part due to expulsion and replacement), but that was offset by prevention of an additional 88 unintended pregnancies over 2 years per 1,000 women.

  Another model found that immediate insertion of contraceptive implants was associated with a higher cost at insertion ($1,091 per patient for immediate placement vs. $650 per patient for delayed placement, likely due to more implants placed in the immediate group) but was more effective in preventing pregnancies, saving $1,263 per patient.

 This prevented 191 unintended pregnancies per 1,000 women with a total savings of $1,263,000 compared with delayed insertion. One caveat is that savings may depend on payor; a 2009 cost-benefit analysis estimated that a postpartum IUD program for patients with Emergency Medicaid would be costly to individual hospitals with a loss of 70 cents per $1 spent.

 Conversely, the same program funded by the state government would save an estimated $2.94 for every $1 spent. This difference was attributed to the likelihood that the state would cover all costs of future unintended pregnancies but hospitals would not see future profits from same-hospital deliveries.

Challenges and barriers to postpartum LARC utilization


	In a 2018 survey of 104 practicing Fellows and Junior Fellows of ACOG, physicians identified lack of access to devices in the hospital, cost or reimbursement issues, and lack of training as perceived barriers to providing immediate postpartum LARC.

 Of those surveyed, only 26.9% were currently offering this service to their patients. Reimbursement can be challenging as compensation for devices and insertion fees are not included in many global payment packages for delivery and postpartum care. Medicaid policies vary widely by state. Policy-level barriers identified in a 2015 survey of 40 Medicaid agencies included lack of accurate understanding of clinical benefits by policymakers; uncertainty about cost-effectiveness, upfront costs, and the overall financial impact of instituting such programs; concerns about making changes to payment methodology from global charges to itemized payments; and competing priorities for Medicaid funds.

Implementing an immediate postpartum LARC program within an individual institution has similar barriers; Hofler et al. in 2017 interviewed personnel from 10 Georgia hospitals working to establish these programs and found that lack of knowledge, financial concerns, and competing clinical and administrative priorities were roadblocks to program success.

 These programs also require collaboration and buy-in at multiple levels by clinicians, patient care team members, pharmacists, administrators, and billing and electronic health record staff, which can be challenging to coordinate. ACOG recognizes these challenges and provides resources through the Postpartum Contraceptive Access Initiative to assist providers who want to implement a postpartum LARC program at their institution.

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Besides routinely offering postpartum LARC to their patients, ob/gyns must advocate for policies that support these devices.

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