An extremely rare case of superfetation in a surrogate mother leading to legal custody issues

Jessica Allen with her family, Malachi is on the left side of screen. 

A California woman got pregnant when she was already pregnant under a surrogacy contract that resulted in ‘Twin Pregnancy’ with two different set of parents.

Jessica Allen, 31- year old agreed to be a surrogate for a Chinese couple, through a surrogacy agency in Southern California.  Surrogacy is legal in some states in US, including California, but it is illegal in China. 

In April 2016, Jessica underwent a single embryo transfer with the Chinese couple’s embryo after a successful IVF.

At six weeks of pregnancy, she was told that she is carrying twins. She was a bit scared, but the Chinese couple was thrilled. She and her partner thought that the embryo must have split into two after implantation. Her $30,000 payment, including expenses —was increased by $5,000 for the second child.

She denies that throughout her prenatal period, none of the staff and physician at the hospital told her that the babies were in separate sacs.

In December 2016, she gave births to both babies by C-section at a hospital in Riverside, California. As per her legal contract with the surrogate agency, she was not allowed to see the babies. She did briefly see a cell-phone picture and did notice that they looked different.

On January 2017, she received a message from the Chinese couple that the twins look different, along with a picture.

“They are not the same, right?” the message read, according to the New York Post. “Have you thought about why they are different?”

A DNA test soon followed and revealed that one of the twin was indeed Allen and Jasper’s biological son. Despite using condoms, she has become pregnant with her own son, after being already pregnant with the Chinese couple baby.

Courtesy: Victoria Roberts

What followed was a lengthy, expensive legal battle, but she finally won the case and got her son back in February 2017. She and Jasper renamed their newest family member Malachi, and he is now 10 months old.

Superfetation is common among mammals, but in order for superfetation to occur in humans, three seemingly impossible things need to happen at the same time: ovulation must take place during an ongoing pregnancy, sperms must somehow penetrate the blocked cervical canal with thick mucus plug and travel all the way into the fallopian tube and finally, the embryo should  successfully implant itself in an already-occupied uterus. The odds of all three of them happening together are very rare, making it an extremely rare occurrence.

A 2008 paper in the European Journal of Obstetrics and Gynaecology, mention that this phenomenon is so rare that only 10 documented cases are mentioned in literature so far.

A review of literature showed that superfetation is mentioned in some case of ARTs.

In the meantime, this case should be a "reason for pause and thoughtfulness" among physicians and surrogacy organization to check for superfetation in unexpected twins in a surrogate mother said Dr. Saima Aftab, medical director of the Fetal Care Center at Nicklaus Children's Hospital, who was not involved in Allen's case.

Vaginal Progesterone supplementation decreases preterm births, neonatal morbidity and mortality in women with twin gestation and short cervix: an updated meta-analysis of individual patient data

Administration of vaginal progesterone to asymptomatic women with a twin gestation and a sonographic short cervix (cervical length ≤ 25 mm) in the mid-trimester reduces the risk of preterm birth occurring at < 30 to < 35 gestational weeks, neonatal mortality and some measures of neonatal morbidity, without any demonstrable deleterious effects on childhood neurodevelopment.

The article was published online in Ultrasound in Obstetrics and Gynecology, the official journal of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG).

The meta-analysis included the results of 6 studies, encompassing 303 women pregnant with twins, all of whom had a cervical length of 25 mm or less in the midtrimester. Of these, 159 women received vaginal progesterone and 144 received a placebo or no treatment. Women who received vaginal progesterone were 31 percent less likely to deliver before 33 weeks of pregnancy (31 percent for those receiving vaginal progesterone, compared to 43 percent for those who did not). Vaginal progesterone also reduced the rate of preterm delivery before 32 weeks and 34 weeks. All results were statistically significant.

The risk of preterm birth < 33 weeks was reduced by 31% and neonatal death by 47% and also reduced the rate of respiratory distress syndrome (RDS), birth weight < 1500 g and use of mechanical ventilation.

No significant difference in the risk of neurodevelopmental disability at 4–5 years of age between children exposed prenatally to vaginal progesterone and those exposed to placebo.

“The findings represent persuasive evidence that treatment with vaginal progesterone in women with a short cervix and a twin gestation reduces the frequency of preterm birth, neonatal complications such as respiratory distress syndrome, and importantly, neonatal death,” said the study’s first author, Roberto Romero, M.D., Chief of the Perinatology Research Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD/NIH). Dr. Romero emphasized that individual patient data meta-analyses represent the “gold standard” in the hierarchy of scientific evidence to answer clinical questions.

Access the full article.

Access the press release.

The accompanying videoclip by the  ISUOG summarizes the importance of research. 

Twins with cephalic first is not a Per Se Indication for planned Cesarean Delivery.

http://www.keywordsuggests.com

Vaginal delivery in twins more than 32 weeks is safer and associated with less neonatal morbidity and mortality as compared to cesarean section when the first twin is cephalic reports authors of large prospective population-based cohort study published ahead of print in Journal of Obstetrics and Gynecology.

Dwight J. Rouse, M.D writes in an accompanying editorial that in the year 2014, 75% of more than 135,000 twin deliveries were by cesarean section in USA. The results of the study show   "a lower rate of [caesarean] delivery in women carrying twins is not only achievable, but that it is also safer for their neonates."

This JUmeaux MODe d'Accouchement (JUMODA) study was multicentric, conducted across 176 maternity units in France and recruited patients from February 2014 to March 2015. All women with twin pregnancies and their neonates born at or after 32 weeks of gestation with a cephalic first twin were included in the study. (n= 5,915)  

Maternity units with more than 1500 annual deliveries were called to participate. The obstetrician completed an online survey after the twin delivery categorizing whether it was a planned vaginal or cesarean labor and what was the actual mode of delivery.

Of the total 5915 study participants, 1,454(25%) women were planned to be delivered by cesarean section and 4,461 (75%) were scheduled to undergo a trial of vaginal birth. Of the 4,461 (75%) planned for vaginal births, nearly (3,583 )80% delivered both twins vaginally.

Ultimately, 61% of twins in this large cohort delivered vaginally. The composite study outcome was intrapartum neonatal mortality, Apgar score at 5 minutes < 4, birth trauma or respiratory and neurological complications.

Overall the infants born by cesarean section had 2.38 times higher odds of suffering one or more of the study outcome as compared to infants born by vaginal route. (OR, 2.38; 95% confidence interval [CI], 1.86 - 3.05).

As the patients were not randomized, the researchers did a propensity score matching to eliminate this limitation. In this matched analysis also, infants born by planned cesarean section had 1.85 times higher odds of suffering one or more of the study outcome as compared to vaginal delivery (OR, 1.85; 95% confidence interval 1.29-2.67).

The researchers also did a subgroup analysis by excluding pregnancies who were high risks. The results showed that in these low risk group planned cesarean was associated with increased neonatal mortality and morbidity only between 32 0/7 and 34 6/7 weeks of gestation.

To conclude:  According to the study a planned vaginal delivery rather than a planned cesarean delivery between 32 to 37 weeks of twins’ gestation with cephalic first, can be attempted and it does not result in high neonatal morbidity and mortality, which is in accordance with the recent American College of Obstetricians and Gynecologists recommendations.

ACOG guidelines for twin delivery says “Perinatal outcomes for twin gestations in which the first twin is in cephalic presentation are not improved by cesarean delivery. Thus, women with either cephalic/cephalic-presenting twins or cephalic/noncephalic presenting twins should be counseled to attempt vaginal delivery.”

Planned cesarean delivery is associated with higher neonatal morbidity and mortality only in twins born before 37 weeks of gestation in overall study cohort and less than 35 weeks in low risk cohort.

In a hospital set up where appropriate facilities with skilled personnel are available, in twin pregnancy with cephalic first and gestational age > 32 weeks, the default plan should be an attempt at vaginal delivery, regardless of presentation of the second twin.

ASRM's guidelines for the limits on the number of embryos transferred in In Vitro Fertilization (IVF) cycles.

courtesy: https://sickbayby.wordpress.com/tag/multiple-gestation/

In order to promote singleton pregnancies and bring down the number of multiple pregnancies in patients undergoing IVF, American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) updated the guidelines regarding the upper limit number of embryos transferred in IVF cycle. These guidelines replace the previous guidance issued in 2013.

The guidelines were  published online in the forthcoming issue of Journal of Fertility and Sterility.

The incidence of triplets and higher order multiple births have essentially declined in US for the last 15 years after steadily rising fourfold during the 1980s and 1990s. But, still multiple births are not desirable outcome of ART therapy.

The rise was due to older maternal age and increased use of ARTs, with no guidelines on the number of embryos transferred.

                                                     

Triplets

Triplets and Higher order births continue to have poor prognosis with 7% succumbing in first year of life as compared to .5% of singleton pregnancies. The ideal outcome after an ART procedure is to have a singleton pregnancy.

National data from CDC in 2013 demonstrate that clinics that perform higher rates of elective single-embryo transfer (eSET) in women aged <38 years have decreased rates of multiple gestation, with no significant impact on cumulative live-birth rates.

In women who are 42 years or younger transferring a single euploid blastocyst resulted in pregnancy rates similar to transferring two untested blastocysts while dramatically reducing the risk of twins.

Patient has the choice to choose the number of embryos transferred but it should be a fully informed decision taking into consideration medical, ethical and financial aspects of the procedure.

For drafting the recommendations, the patients have been categorized into favorable prognosis group and all others.

Conditions associated with favorable outcome are young age: euploid embryos, one or more good quality embryo available for cryopreservation and previous history of livebirth after an ART cycle.

For frozen embryo transfer the favorable conditions are when high quality, vitrified, day 5 or 6 blastocysts available.

The number of embryo transferred should be agreed upon by the treating physician and patients, depending upon the patient characteristics, data for the individual procedure and data from the ART services provided by the clinic. The following guidelines recommend the upper limits of the number of embryo transferred.

Patient with favorable prognosis:

A single euploid embryo transferred in patient of any age has the most favorable prognosis.

Patients under the age of 35 are always encouraged to receive one single embryo, irrespective of the embryo stage.  

Similarly, for patients between 35-37 years of age, a single embryo transfer is encouraged.

Patient between 38-40years of age, a single euploid embryo should be transferred, if availability is restricted than three cleavage-stage embryos or two blastocysts should be transferred.

Similarly, for patients between 41-42 years of age, the choice is to transfer single euploid embryo, if not than four cleavage-stage embryos or three blastocysts is the second choice.

Other scenarios:

In each of the above age group, if the patients do not belong to favorable prognosis category they can receive an additional embryo based on individual circumstances.

If patients who are in favorable prognosis category but fail to conceive after repeated cycles than an additional embryo may be transferred. If these patients have some coexisting medical condition that put them at high risk because of multiple gestation, a single embryo transfer is recommended.

In cases where the number of blastocysts transfer exceed the recommended limit, patient should receive counselling and everything should be well documented on the medical record.

Patients who are more than 43 years of age, insufficient data exist for number of embryos to be transferred using her own oocytes. The risk of multiple pregnancy increases dramatically as age increases, so caution must be exercised.

In donor-oocyte cycles decision should be made according to donor's age.

In frozen embryo transfer cycles, the patient should be categorized into favorable/other scenarios  group according to age of women when the embryo was frozen. And the number of frozen embryo transferred should not exceed the number of fresh embryo transfer recommended for each age group.

The full article in the Journal of Fertility and Sterility can be accessed here.

Vaginal delivery in twins increases risk of maternal morbidity as compared to elective C-section.

A 7-year assembled retrospective cohort study of women with vertex presenting twin who underwent vaginal delivery have higher incidence of maternal morbidity as compared to women delivered by C-section.

The findings of this study was published on-line on January 9,2017 in Obstetrics andGynecology Journal.[1]

Guidelines suggest an attempt at vaginal birth if first twin is vertex with no uterine scar or other contraindication exits. Many  studies have compared neonatal mortality and morbidity but not much information is available on maternal morbidities based on route of delivery in twins.

 Dr. Sarah Rae Easter of Brigham and Women's Hospital and Harvard Medical School in Boston is the lead author of the study. She and her colleagues carried out the study from 2007-2014. Out of 2,272 twin pregnancies beyond 32 weeks of gestation, 1,140 (50%) met inclusion criteria of no uterine scar and no other contraindication for vaginal birth.  571 (50%) women chose to have elective cesarean delivery and 569 (50%) underwent a trial of labor to attempt vaginal birth. 

In the trial of vaginal birth group, 74% had an uneventful vaginal delivery, while others required operative assistance or breech extraction.

After adjusting for confounders, trial of labor group  had higher rate of maternal morbidity (12.3%) as compared to elective C-section group (9.1%). The rates of Postpartum hemorrhage were nearly twice in women having vaginal births.3% of women had major lacerations of genital tract.

An earlier RCT published in BJOG by Hutton EK et al did not show any difference in maternal morbidities in elective C-section vs Vaginal delivery group. [2]

Dr. Easter did not advice against trial of labor in twins, but wanted the clinicians to be more cautious while counselling the patients. She quoted. "Though our findings suggest a trend towards increased maternal morbidity in those who labor, we do not see this as a deterrent to twin vaginal delivery, we feel the immediate increased risk of postpartum hemorrhage should be balanced with the benefits of a vaginal birth. We hope clinicians will thoughtfully incorporate our findings into counseling while keeping in mind the known long-term consequences of Cesarean delivery and its impact on future pregnancies."

“Delivery in hospitals equipped to manage postpartum hemorrhage is of equal importance for mothers attempting vaginal birth of twins” she further added.

The authors concluded “In pragmatic terms, the tradeoff for a 74% chance of vaginal delivery is a 4% absolute increase in the rate of serious postpartum hemorrhage.”

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[1] http://journals.lww.com/greenjournal/Abstract/publishahead/Association_of_Intended_Route_of_Delivery_and.98512.aspx

[2] https://www.ncbi.nlm.nih.gov/pubmed/26328526

Predicting spontaneous preterm birth in twin pregnancies utilizing cervical length and gestational age: Individual patient data meta-analysis.

Multiple births are steadily climbing all around the world. Developed countries making a significantly higher contribution to this rising rate because of women delaying childbirth, elderly mothers and increased use of ARTs.

US twinning rate rose by 101% from 1980 – 2006. About 68,339 twins were born in 1980 that doubled to 137,085 in 2006. The US current twin birth rate is 33.9 per 1,000 live births.

 According to WHO the rate of singleton preterm birth ranges between 5% to 18% for singleton pregnancy worldwide, the average being 11%, while almost 60% of twins are delivered preterm. About 13% of twins are born before 34 weeks and 7% before 32 weeks.

A multitude of prophylactic therapies have been in use like to gain valuable gestational weeks by supplementing progesterone, vaginal pessaries and strict bed rest without substantially significant results.

The next step was to develop essential biomarkers that can predict the chances of preterm births. Cervical length(CL) has long   been used as a predictive indicator of preterm birth. An earlier review has shown that a CL < or=20 mm at 20-24 weeks' gestation was the most accurate in predicting preterm birth at <32 and <34 weeks respectively. Many other studies have combined fetal fibronectin with CL. 

Studies in singleton pregnancies have also shown that the relationship between CL and spontaneous preterm birth (sPTB) is dependent on the Gestational age (GA) at which the USG is done, a shorter CL early in pregnancy has greater significance than the same measurement at a later GA.

Such studies in twins are few with small sample size and are not comparable. Previous meta-analysis has shown a relationship between CL and sPTB in twins, but did not correlate the GA at screening with prediction of sPTB.

This recent study published in the May, 2016 issue of BJOG is a meta-analysis of independent patient data(IPD), and provides a new estimate in which CL and GA are treated as continuous variables to predict weeks at delivery.

Specific data collected for each patient from the original authors of the study included the exact GA at CL screening, the CL measurement in millimeters and the exact GA at birth in weeks and days.

23 studies met the inclusion criteria, resulting in a total of 6188 transvaginal scans, performed on 4409 twin pregnancies. 

In the first analysis, univariate regression was performed to see what other confounders like maternal age, ethnicity, smoking, BMI, chorionicity, parity and study location affects the GA at birth. 

As second analysis multinomial logistic regression model was derived predicting the probabilities of very early preterm, early preterm, late preterm, and term birth using GA at USG and CL as continuous variables.

Important study results were:

• BMI was the only other variable that correlated significantly with GA at birth in the univariate analysis, but when it was incorporated into multinomial logistic regression model with CL and GA at ultrasound, prediction of GA at birth did not improve.
• A short CL measured at ≤20⁺⁰ weeks by USG indicates a probability of birth significantly earlier than if the same CL was taken at a later GA.
• When screening before 18⁺⁰ weeks, any cervical length <30 mm has a higher risk of sPTB at ≤28⁺⁰ weeks in twins than in singletons.Whereas the best prediction of birth between 28⁺¹ and 36⁺⁰ weeks was provided by screening at ≥24⁺⁰ weeks.
• A 100% probability of preterm birth not occurring before 28 weeks is achieved by CL of 65 mm and 43 mm at ultrasound GA at ≤18⁺⁰ weeks and at 22⁺¹ to 24⁺⁰ weeks, respectively.

In the third analysis, the accuracy of the model to correctly predict term delivery as compared to preterm was assessed. The model has a 68.2% true negative rate, classifying correctly those who were predicted to deliver at ≥36⁺¹ weeks, compared with 26.2, 13.3 and 36.2% correctly predicted to deliver at ≤28⁺⁰, 28⁺¹ to 32⁺⁰ and 32⁺¹ to 36⁺⁰ weeks, respectively (true positive rate).

Although effective intervention for sPTB in twins are limited, the study provides risks of very early, early and late preterm birth, so a personalized cost effective delivery plan, optimal timing of corticosteroids and referring to neonatal unit can be managed. It also justifies serial CL measurements, so that early and late sPTB could be predicted.

To conclude the authors, recommend to start the screening at ≤18⁺⁰ weeks with repeat screening at >22⁺⁰ weeks; this best identifies the patients that may deliver very early at ≤28⁺⁰ weeks as well as the more common later group of sPTB between 28⁺⁰ to 36⁺⁰ weeks. 

References:

http://www.cdc.gov/nchs/fastats/multiple.htm

http://www.who.int/mediacentre/factsheets/fs363/en/

http://www.ncbi.nlm.nih.gov/pubmed/24360590

http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.13575/full

http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.13710/full