Showing posts with label corticosteroids. Show all posts
Showing posts with label corticosteroids. Show all posts

Saturday, December 8, 2018

First live birth following a uterine transplant from a deceased donor


A Brazilian woman becomes the first person to successfully give birth to a healthy baby after receiving a uterine transplant from a deceased donor. This comes after a history of previous 10 unsuccessful attempts at live birth after deceased donor transplants in the United States, the Czech Republic, and Turkey.

This is a milestone in the history of uterine transplants as it opens the path forward for achieving successful pregnancies without the need of live donor and donor surgery. The details of the case were published by the Lancet on December 4, 2018, accompanied by an editorial.

Dr. Dani Ejzenberg, PhD, the lead author and researcher from the Department of Obstetrics and Gynecology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, said in a press release by Lancet, "The use of deceased donors could greatly broaden access to this treatment, and our results provide proof-of-concept for a new option for women with uterine infertility."

Ejzenberg and colleagues report that the 32-year old woman was born without a uterus because of congenital uterine agenesis, also called as Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, which affects 1 in 4500 women.

The woman received uterus in September 2016 after 10.5-hour surgery from a 45-year old multiparous woman who died of subarachnoid hemorrhage. After the transplant, the woman was discharged on the 8th postoperative day with immunosuppression achieved and maintained with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF) when at five months post-transplant, azathioprine replaced MMF.

The woman got her first period 37 days after transplant and after that continued to have regular cycles every 26–32 days.  Pregnancy occurred following single embryo-transfer after seven months from cryopreserved blastocyst from a successful in-vitro fertilization four months before the transplant surgery.

The pregnancy progressed uneventfully and was monitored by ultrasound and Doppler flow velocity waveforms of uterine arteries, fetal umbilical, or middle cerebral arteries.

A healthy, female baby weighing 2550 g was delivered by elective cesarean section at 36 weeks on December 15, 2017. At the time of writing the article, the baby is healthy and developing normally.

The uterus was also removed at the time of cesarean section, and immunosuppressive therapy stopped.

Cesar Diaz-Garcia, MD, Nuffield Department of Women's and Reproductive Health, University of Oxford, UK, and Antonio Pellicer, MD, PhD, Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Spain, writes in an accompanying editorial, "In a context in which the scarcity of human data is still the norm, [the report] reveals a breakthrough in the field of uterus transplantation."

The first uterine transplant from a living donor took place in Sweden in 2013, followed by first live-birth after transplant in 2015. Since then, 11 more births have taken place worldwide, albeit all from live donor transplant.

However, uteri from living donors are limited because the person has to a relative of the recipient, thereby, limiting the option for women with uterine factor infertility. If uterine transplant after dead donor becomes successful, uteri will not be in short supply as people are more willing to donate organs after death than when they are alive.

The authors agree that many potential issues need to be addressed before deceased donor transplant becomes a norm. These include standardization of operative procedures, immunosuppressive therapy before and during pregnancy, criteria for rejection if it happens, and long-term outcome of the baby delivered after transplant.



Wednesday, September 28, 2016

ACOG updates the committee opinion and expands antenatal corticosteroids recommendations for late preterm births.

American College of Obstetricians and Gynecologists (ACOG) recently updated its committee opinion for administration of prenatal corticosteroids and expanded it to high risk women for late preterm birth (34 0/7 - 36 6/7 weeks).

“Providing women’s health care providers with evidence-based techniques to successfully manage instances of preterm birth is a top priority for ACOG,” said one of the Committee Opinion authors, 

Dr. Yasser El-Sayed, MD, FACOG. “Through the new committee opinion we are expanding an existing therapy, based on recent data, to improve outcomes in more clinical settings. It’s an important step in getting more mothers and babies the care they need to be healthy.”[1]

This new Committee Opinion replaces ACOG’s Practice Advisory on Antenatal Corticosteroid Administration in the Late Preterm Period, originally issued on April 4, 2016.[2]

These recommendations follow the results of significant Antenatal Late PretermSteroids (ALPS) trial, published earlier this year.[3] The committee opinion now includes recommendations that support the administration of antenatal corticosteroids in certain populations during the late preterm birth period, or between 34 and 37 weeks of gestation.

The recommendation also holds good in multiple gestation.

Corticosteroids given late preterm significantly reduced the rate of neonatal respiratory complications like transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia. Studies also show lower rates of intracranial hemorrhage, necrotizing enterocolitis, and mortality. The only side effect is neonatal hypoglycemia which should be monitored closely.

As per the news release “The document also re-emphasizes ACOG’s recommendation to consider antenatal corticosteroids for pregnant women at risk of preterm delivery starting at 23 weeks of gestation, based on a family’s decision regarding resuscitation.”

The ACOG recommendations in the October issue of journal of Obstetrics and Gynecology[4]: It states: 

  • A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations. It may be considered for women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days, based on a family’s decision regarding resuscitation. 
  • A single course of betamethasone is recommended for pregnant women between 34 0/7 weeks and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.
  • Treatment should consist of either two 12-mg doses of betamethasone given intramuscularly 24 hours apart or four 6-mg doses of dexamethasone administered intramuscularly every 12 hours.
  • Scheduled repeat course or serial courses are not recommended.
  • A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days, and whose prior course of antenatal corticosteroids was administered more than 14 days previously. Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario.
  • Evidence is insufficient at present for giving a rescue or repeat course in patients with preterm pre labor rupture of membranes (PROM), hence no recommendation is made.
  • ACOG advocates continuous long term monitoring of patients who received corticosteroids.  




[1]http://www.acog.org/About-ACOG/News-Room/News-Releases/2016/ACOG-Improves-Outcomes-for-Preterm-Births
[2] http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Antenatal-Corticosteroid-Administration-in-the-Late-Preterm-Period
[3] http://www.nejm.org/doi/full/10.1056/NEJMoa1516783#t=article
[4] http://journals.lww.com/greenjournal/Fulltext/2016/10000/Committee_Opinion_No_677___Antenatal.62.aspx

Thursday, November 19, 2015

Uterine Transplant-------Is this the final frontier!



Cleveland Clinic announced Thursday the launch of a “groundbreaking” research study that will perform uterus transplants in 10 women. The first operation is expected to take place within the next few months, the New York Times reports.

Since the 1970s a number of teams around the world have been researching the possibility of developing a womb transplant procedure.

Transplant research, as a whole, has also tended to focus on life-saving transplantation (heart, kidney, liver) with womb transplant research being rather limited especially following advances in IVF techniques.

We have come a long way since 1905 which saw the first successful corneal transplant.

In 2000 the world’s first womb transplant was performed on a 26 year old woman in Saudi Arabia. But, the transplanted womb only lasted for 99 days.

In December 2010, our colleagues in Sweden were able to report a pregnancy as a result of a womb transplant on a rat.

In September 2014, Mats Brännström and colleagues report the first successful birth of a child following uterus transplantation. The recipient, a 35-year-old woman lacking a uterus (Rokitansky syndrome), received a cryopreserved embryo 1 year after transplantation, leading to a livebirth by caesarean section.
The first uterine transplant baby being delivered by Cesarean Section .    



The donated uterus came from the woman’s own mother, so the baby is also the first born to a woman using the same womb from which she emerged herself.

This team has since performed a total of nine uterus transplants that have resulted in five pregnancies and four live births.

This report marks an important development that will give women with congenital or surgical absence of the uterus an opportunity to give birth to a child.

The first clinical trial of uterus transplantation in the United States has begun at Cleveland Clinic in Ohio, where the process of selecting women to participate in the study is now under way.

The ground-breaking study will include 10 women with uterine factor infertility (UFI), a condition in which a woman was born without a uterus, has lost her uterus, or has a uterus that no longer functions.

It's thought that as many as 50,000 U.S. women might be potential candidates for the procedure.


Complex Protocol of the study 
After being approved for the trial, the woman follows a complicated protocol:
  • Clinicians begin the in vitro fertilization process by stimulating the woman's ovaries to produce multiple eggs.
  •  After retrieval of the woman's eggs, they are fertilized with sperm in a laboratory and frozen.
  •  After 10 embryos have been frozen, Lifebanc, an organ procurement agency, starts searching for a donor.
  •  When a uterus donor has been found, that person's next-of-kin signs an informed consent for the organ donation.
  • The donor uterus is transplanted into the patient's pelvis within 6 to 8 hours after harve
  • The transplanted uterus is allowed to fully heal over 12 months.
  •  After 1 year, the woman's frozen embryos are thawed and implanted, one at a time, into the woman until she becomes pregnant.
  • The woman takes Immunosuppressant drugs during her pregnancy.( tacrolimus, azathioprine, and corticosteroids).
  • A high-risk obstetrics team monitors the woman throughout pregnancy and childbirth.
  • The woman undergoes a cervical biopsy each month to monitor for organ rejection
  • An obstetrician delivers the baby by cesarean section.
  • After the woman has one to two babies, she undergoes a hysterectomy and stops taking Immunosuppressant drugs to reduce her long-term exposure to the medications.

Uterine Transplants are Unique in the sense that unlike any other transplants, they are ‘ephemeral,'” Cleveland Clinic lead researcher Andreas Tzakis said in the release. “They are not intended to last for the duration of the recipient’s life.” 

After 1-2 healthy pregnancies the transplanted uterus is either removed or allowed to disintegrate.

Vincent, One year now

Now, Vincent the first Baby born after uterus transplant is healthy one year old and the team of Dr.  Mats Brännström, the Swedish professor in obstetrics and gynecology of the University of Gothenburg and Sahlgrenska University Hospital, are looking forward to improve the technique and reduce the surgical procedure time.


References:










All Photos courtesy by Martin Valigursky/iStock/Getty Images