One week ago I was had an ectopic pregnancy in the left fallopian tube
at the same time a normal twin pregnancy (8 weeks into gestation with
an ultrasound scan a few hours prior to surgery confirmed these facts)
in the uterus.  Bleeding and abdominal pain increasingly presented for
two weeks prior to surgery.  Emergency surgery (3-hour surgery started
as a 1-hour
laproscopic procedure but ultimately required an abdominal incision
for access to all damaged areas)resulted in the removal of the
ruptured fallopian tube, associated blood clot in the abdominal cavity
and loss of one twin (one day after surgery).  Two days after surgery
an ultrasound scan showed normal heart-beat for the surviving twin.  I
have had no prior pregnancies, abdominal surgeries and no history of
ectopic pregnancy in my family.
My questions are:
(1)  What is the probability of this condition (ectopic plus uteran
pregnancy) occuring at the same time?
(2)  What is the probability that the surviving twin will not survive to birth?
(3)  What is the probability that the surviving twin will have been
damaged due to drugs administered during and after surgery, surgical
process, etc?  How can this damage, if any, be determined?
Thank you.
PS:  Please, no lectures or answers that tell me to just "ask my doctor".

---

Clarification of Question by monsterthecat-ga on 18 Sep 2005 20:44 PDT

Would in vitro fertilization (IVF) process make any known (i.e.,
documented) difference in the probability of the ectopic prognancy
occurring with the pregnancy in the uterus?

Also, my question has been locked for over two days, the Google time
limit is 8-hours.  Please unlock it so other researchers can attempt
to answer it and users can post comments.

---

Request for Question Clarification by czh-ga on 19 Sep 2005 00:42 PDT

Hello monsterthecat-ga,

I?m sorry about the medical difficulties you?ve had because of your
ectopic pregnancy and the losses you?ve suffered. My research so far
has led to answers to some, but not all, of your question.

Question 1
I can provide you with fairly detailed information about the
probability of heterotropic pregnancies, i.e., concurrent ectopic and
intrauterine pregnancy. The statistics have been changing in recent
years because of the role of reproductive technologies and IVF
procedures. How old are you? Were you treated for infertility? Is your
pregnancy a result of IVF?

Question 2
I?ve found some studies that provide fairly consistent statistics on
the survival rates for intrauterine pregnancies after the termination
of the concurrent ectopic pregnancy.

Question 3
I believe it would be difficult, if not impossible, to provide you
with meaningful information about the condition of your surviving twin
since you did not say what drugs were administered during and after
the surgery. At best, I can probably find some general information
about what procedures and medications might impact the course of the
pregnancy and the condition of the surviving intrauterine fetus.

Please let me know if the above information will be a satisfactory
answer. I look forward to your clarification.

~ czh ~

---

Clarification of Question by monsterthecat-ga on 20 Sep 2005 11:13 PDT

Questin 1 clarification: 
First, isn't the term "heterotopic" NOT "heterotRopic" (your spelling)
pregnancy, please check your spelling as there are over 47 times (267
versus over 12,000 hits) more information based on the spelling I have
noted.   I am 47 years old.  However, keep in mind failure of the
fallopian tubes to operate properly (sweep embryos down the fallopian
tube to the uterus) is a typical issue with increased age so please do
not mix in the age issue unless you find IVF, age, and heterotopic
pregnancy studies together.  A "frozen cycle" IVF cycle was used,
meaning frozen embryos from a prior ovum retrieval (six months
earlier) were used so at the time of embryo transfer I was NOT
receiving ovarian simulation drugs but instead Lupron, a drug that
supresses normal ovulation.  Due to my numerous IVF/IUI failures where
no pregnancies was achieved, six embryos were transferred.  After the
embryo transfer I was taking significant amounts of progestrogen and
estrogen and continue to do so.  These drugs grossly over stimulate
the body to support a pregnancy such as increasing the lining
thickness of the uterus.  Prior to the cycle my hormone levels were
normal.
Clarification for Question 2:
The studies need to indicate that the ectopic pregnancy was treated
via surgery, laproscopic or laprotomy to provide me with an good
comparison basis to myself.
Clarification for Question 3:
The drugs I was taking after surgery were the same as drugs prior to
surgery with the addition of IV demerol for the day of surgery and one
following day.  I do not know the drugs used during surgery.  I
specifically would like to know what neonatal testing would be
recommended above and beyond the traditional tests to check for fetal
development problems.

---

Request for Question Clarification by czh-ga on 20 Sep 2005 12:57 PDT

Hello again monsterthecat-ga,

Thank you for the extensive clarifications. (I?m sorry about the
misspelling in my prior message. My searches were done with the
correct spelling.) I?m getting closer to getting you additional
relevant information.

Please tell me about the course of Lupron treatment you received.
Which form of the drug did you get and what period of time in relation
to the pregnancy were you taking it? [Lupron can be administered as an
intramuscular injection (into muscle), a subcutaneous injection (under
the skin), as a depot injection (a shot given periodically at a
doctor's office), or as an implant.]

What neonatal testing has your obstetrician recommended for your ongoing pregnancy?

More soon.

~ czh ~

---

Request for Question Clarification by czh-ga on 20 Sep 2005 13:30 PDT

Another question, monsterthecat-ga. Were the eggs used in the IVF your
own? Your age has a bearing on this. Thanks.

~ czh ~

Hello monsterthecat-ga,

My heart goes out to you wishing you well for carrying your pregnancy
to term and having the baby you long for. You?ve asked very specific
questions and I?ve collected a selection of authoritative resources
that should give you sufficient information to draw your own
conclusions. Above all, it?s important that you consult your own
doctors for medical guidance in your own case. I am not a doctor and
cannot give you medical advice.

I will give yoU a short summary of my findings and then you can
explore each topic in depth with the websites I?ve listed.

(1)  What is the probability of this condition (ectopic plus uteran
pregnancy) occuring at the same time?

The probability of heterotopic pregnancy was estimated to be 1/30,000
until the late 1940s. Data in the 1980s showed an increase to 1/10,000
and more recent estimates have shown the range to be 1/4,000-7,000. In
the case of assisted reproduction, the rate of heterotopic pregnancies
is shown as 1-8/100 depending on the study. As you can see, the rate
of heterotopic pregnancy for women receiving IVF treatments is very
high. Please see the articles below for up-to-date information.


(2) What is the probability that the surviving twin will not survive to birth?

I?m very sorry to tell you that this is a very high risk pregnancy. It
is difficult to give you a numerical estimate of the probability for
this twin surviving to birth because there are so many unknown factors
involved regarding your specific situation. I will give you the
general findings from my research but you will have to apply the
information I?ve collected and apply it to yourself using the guidance
of your own doctors.

There are some small studies of successful births after laparoscopic
surgery for ectopic pregnancy concurrent with intrauterine pregnancy.
These studies show healthy births in 67-78% of the cases studied.
There is a major caveat to take into account along with these studies.
This is the issue of the consideration of your age in reaching a
successful delivery of your surviving twin.

In your clarification you explained that you?re 47 years old, that you
used 6 frozen embryos in you IVF procedure, and that you had ?numerous
IVF/IUI failures.? All of these factors add a lot of risk to the
pregnancy. I?ve included lots of resources to help you understand how
these conditions impact the likelihood of a successful pregnancy. I
especially call your attention to a very recent study that directly
addresses your question. "One Last Chance for Pregnancy: A Review of
2,705 In Vitro Fertilization Cycles Initiated in Women Age 40 Years
and Above" concludes that the probability of a woman over 45 having a
baby using her own eggs is extremely slim. This conclusion is reached
even without the complicating factor of the ectopic pregnancy and the
loss of one twin. I am terribly sorry to be the conveyor of such bad
news.


(3)  What is the probability that the surviving twin will have been
damaged due to drugs administered during and after surgery, surgical
process, etc?  How can this damage, if any, be determined? What
neonatal testing would be recommended above and beyond the traditional
tests to check for fetal development problems?

The description of your treatment seems normal and appropriate for
your situation. The surviving twin is likely to have suffered some
stress but this is not the major issue in the likelihood of survival.
I?ve collected a variety of resources for evaluating what kind of
neonatal testing you should consider because of your advanced age for
childbirth. The rate of miscarriage for women over 45 is very high.
Because the quality of a woman?s eggs declines with age, the
probability of genetic conditions that might result in early
miscarriage are high. The articles I?ve collected will give you a good
overview of the issues involved and the common testing guidelines for
high risk pregnancies. I suggest that you discuss your continuing
concerns about further testing with your obstetrician.

Dear monsterthecat-ga, I?m very sorry that most of the information
I?ve found for you is not encouraging. I?m sure you had good reason
for deciding to attempt to have a child at this time so there might be
factors that provide more optimistic indicators for you.

I wish you the fulfillment of your dreams with all my heart.

~ czh ~

=========================================================
PROBABILITY CONCURRENT ECTOPIC AND INTRAUTERINE PREGNANCY
=========================================================

http://www.advancedfertility.com/ectopic.htm
Heterotopic pregnancy: Combined intra- and extra-uterine pregnancy
Old (1940's) literature says the rate is 1/30,000 pregnancies.
Current rate is about 1/4000 pregnancies.
Rate is increased with the use of ovarian stimulation.
With IVF, rate is about 1/35-1/100 clinical pregnancies.

-------------------------------------------------


http://www.hypertension-consult.com/Secure/textbookarticles/Primary_Care_Book/112.htm
Ectopic Pregnancy: Part I

An especially problematic and high risk variation of EP is the
heterotopic pregnancy. In this case, a normal uterine pregnancy
coexists with an EP. In 1948, this was a very rare condition and was
reported in only 1 in 30,000 pregnancies.26 However, the ED physician
should be aware that the heterotopic pregnancy is becoming
increasingly common. In this regard, data from the 1980s show a rate
of 1 in 10,000 pregnancies, and the most recent estimates vary from 1
in 3889 to 1 in 6778 pregnancies.27-29 However, in the case of
assisted reproduction, the heterotopic pregnancy rate soars to a
staggering 1-8 per 100 pregnancies.27

-------------------------------------------------


http://medstat.med.utah.edu/kw/human_reprod/lectures/clin_radiology/
First Trimester Ultrasounds
Ectopic Pregnancy 

The most reassuring sign that an ectopic pregnancy is not present is
the sonographic demonstration of a normal intrauterine pregnancy. The
presence of an intrauterine pregnancy decreases the risk of a
concurrent ectopic pregnancy to 1 in 30,000 for a low risk patient and
1 in 5,000 for a high risk patient (history of pelvic inflammatory
disease (PID), previous ectopic, infertility, tubal surgery).
Transvaginal ultrasound, with a reported accuracy of greater than 90%,
should routinely be used in the evaluation for ectopic pregnancy.

-------------------------------------------------


http://www.aafp.org/afp/20000215/1080.html 
American Family Physician, February 2000
Ectopic Pregnancy

Heterotopic Pregnancy
Any discussion of ectopic pregnancy would be incomplete without
mention of heterotopic pregnancy (coexistence of intrauterine and
ectopic pregnancies). In Europe and the United States, this condition
occurs in one of 2,600 pregnancies.34 With fertility treatments, the
incidence of heterotopic pregnancy increases to as high as 3
percent.34 Heterotopic pregnancy is extremely difficult to diagnose,
and 50 percent of cases are identified only after tubal rupture. If
retention of the intrauterine gestation is desired, the ectopic
pregnancy must be treated surgically.1,12

------------------------------------------------


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11155422&dopt=Abstract
Mayo Clin Proc. 2001 Jan;76(1):90-2. 
Interstitial heterotopic pregnancy in a woman conceiving by in vitro
fertilization after bilateral salpingectomy.

Heterotopic pregnancy, defined as the coexistence of an intrauterine
pregnancy and an ectopic pregnancy, occurs in approximately 1 in 100
pregnancies conceived by in vitro fertilization (IVF), particularly
when multiple embryos are transferred into the uterus. The ectopic
gestation of the combined pregnancy usually occurs within the ampulla
of the fallopian tube. If it implants within the interstitial portion
of the fallopian tube, however, the resulting interstitial pregnancy
eventually can rupture through the uterus, leading to sudden, severe
hemorrhage and maternal death. This article describes the rupture of
an interstitial heterotopic pregnancy in a 37-year-old woman
conceiving by IVF after bilateral salpingectomy. The interstitial
pregnancy was removed by laparotomy to protect the intrauterine
pregnancy from damage. Physicians should consider interstitial ectopic
pregnancy as a cause of abdominal pain, even when a viable pregnancy
occurs by IVF after salpingectomy.

PMID: 11155422 [PubMed - indexed for MEDLINE]


===============================================================
PROBABILITY OF SURVIVAL OF INTRAUTERINE PREGNANCY AFTER SURGERY
===============================================================

http://www.ingentaconnect.com/content/repro/rebi/2002/00000005/00000003/art00016
Heterotopic triplet pregnancy: report and video of a case of a
ruptured tubal implantation with living embryo concurrent with an
intrauterine twin gestation

Abstract:
This report presents a case of triplet heterotopic gestation after
intracytoplasmic sperm injection (ICSI)-IVF treatment, with a left
ruptured ectopic tubal implantation with a living embryo and
successful outcome of the concurrent intrauterine twin gestation. A
couple whose infertility was caused by oligoasthenozoospermia was
referred for ICSI treatment. Three good quality embryos were
transferred at the request of the patient. Early gestational control
was performed by ultrasound at weeks 5 and 7 of gestation. The patient
reported to the centre during week 7 with severe abdominal pain and
with signs of peritoneal irritation. Transvaginal ultrasound revealed
an extra-uterine ruptured implantantion. During the concomitantly
performed laparoscopic procedure, a living embryo was observed after
opening the extra-uterine embryonic sac. Heartbeat activity was
present and lasted for 5 min after surgical resection of the tubal
implantation. The patient was discharged from hospital without
complications. The intrauterine twin gestation was not affected and
two healthy infants were born at week 38 of gestation.

-------------------------------------------------


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10438980&dopt=Abstract
Conservative medical and surgical management of interstitial ectopic pregnancy.

There were nine cases of heterotopic interstitial pregnancy. Seven
patients were managed with potassium chloride injected into the
ectopic pregnancy, and two patients were treated by laparoscopy.
Overall, 67% of the coexisting intrauterine pregnancies resulted in
successful deliveries and the remainder ended in spontaneous
abortions.

-------------------------------------------------


http://www.rscbayarea.com/articles/ectopic_pregnancy.html
Ectopic Pregnancy
Surgical vs. Medical Therapy
Current Evidence-Based Review of the Medical Literature 

Introduction
Any pregnancy located outside of the uterine cavity is defined as an
Ectopic Pregnancy (EP). The vast majority (99%) of EP's occur in the
fallopian tube ("tube") and ectopics currently account for 1-2% of all
pregnancies. Ectopic pregnancies are potentially life-threatening, and
more than 100,000 cases occur annually in the United States 1. The
incidence of EP continues to increase yearly due to the occurrence of
sexually transmitted diseases, prior salpingitis (tubal infections),
IUD use, pelvic adhesions and other causes. The death rate from EP is
about 0.3% 2.

Heterotopic Pregnancy
As mentioned above, the presence of both an intrauterine pregnancy and
an ectopic pregnancy at the same time is termed a heterotopic
pregnancy. Because most of these occur with ART procedures, an
ultrasound exam of the woman's uterus should be done before surgery
for removal of the ectopic pregnancy. This will result in a 67% term
delivery rate of the normal intrauterine pregnancy 19. MTX therapy
cannot be used with heterotopic pregnancies as it will terminate both
gestations.

-------------------------------------------------


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11048410&dopt=Abstract
[Heterotopic pregnancy and its occurrence in assisted reproduction]
[Article in Czech]
Hulvert J, Mardesic T, Voboril J, Muller P.
Sanatorium Pronatal, Praha.

OBJECTIVE: To assess the incidence of heterotopic pregnancy after
infertility treatment using the technology of assisted reproduction.
DESIGN: A prospective study of 618 women who became clinically
pregnant following assisted reproduction technology (ART) procedures.
SETTING: Sanatorium Pronatal, Na dlouhe mezi 4/12, 147 00 Praha 4-Hodkovicky.
METHODS: Study group consists of clinical pregnancies conceived after
ART procedures within the period from January 1, 1997 until June 30,
1998. A condition to be included in survey group was that there was a
gestation sac detected by ultrasound or histological confirmation of
ectopic pregnancy.
RESULTS: Six-hundred-eighteen clinical pregnancies resulted and 23 of
the pregnancies were ectopic gestations (3.7%). Seven out of the 23
(30.5%) ectopic pregnancies were heterotopic. Thus heterotopic
pregnancy rate after ART was, 1.14% (1 in 88).
CONCLUSION: The incidence of heterotopic pregnancy following assisted
reproduction technique is relatively frequent. This condition
represents a live-threatening complications of pregnancy. The
prognosis for intrauterine gestation in case of heterotopic pregnancy
is usually good. About 78% delivered living child at term.

-------------------------------------------------


http://www.liebertonline.com/doi/abs/10.1089/104240603763487186?journalCode=gyn 
Journal of Gynecologic Surgery
Laparoscopic Treatment of Heterotopic Pregnancy
Mar 2003, Vol. 19, No. 1: 49-52 
Savvas Efkarpidis, MD, Evangelos  Alexopoulos, MD, PhD, MRCOG,
Panayiota Antoniadou, MD, David Liu, MD, FRCOG

Heterotopic pregnancy poses difficulty for diagnosis and for
management. The challenge is to treat the ectopic component without
risking the mother and ensuring the intrauterine conception progresses
safely to full term. There are no studies comparing the various
treatment modalities and their outcomes. The authors present a case of
laparoscopic treatment of heterotopic pregnancy and literature review.

-------------------------------------------------


http://www.obgmanagement.com/content/obg_featurexml.asp?file=2002/10/obg_1002_00036.xml
Volume 14, No. 10 October 2002 
Heterotopic pregnancy: an emerging diagnostic challenge 

Due in part to rising rates of in vitro fertilization, heterotopic
pregnancy isn?t nearly as rare a condition as it was in times past.
Here, the authors detail protocols for diagnosing and treating this
challenging disorder.

Final thoughts 
It is important to note that one-third of intrauterine pregnancies
accompanying heterotopic pregnancy miscarry in the first (89%) and
second trimesters (8.5%). Miscarriage beyond the second trimester is
rare, though preterm delivery may occur-particularly when heterotopic
pregnancy is accompanied by multiple births. Still, a full two-thirds
of intrauterine pregnancies accompanying heterotopic pregnancy do
survive to term.

-------------------------------------------------


http://eastcoastivf.com/Super_Ovulation.html
Superovulation/Ovulation Induction

POTENTIAL RISKS AND DISADVANTAGES
The development of a pregnancy following ovulation induction treatment
is dependent on many factors, some of which include: the age of the
woman, the diagnosis, the number of previous cycles of treatment, the
number and quality of the eggs and the quality of the semen sample.
There are many complex and sometimes unknown factors which may prevent
the establishment of pregnancy.


======
LUPRON
======

http://www.stronghealth.com/services/womenshealth/ivf/currentpatients/ovulationinduction/lupron.cfm
Lupron
Description
GnRh agonist

Purpose
Lupron is used to prepare the ovaries for stimulation with fertility
medications. Lupron temporarily shuts down the messages from the brain
to the pituitary gland, which then shuts down FSH and LH production.
Without the production of these hormones, the ovaries can?t produce
the necessary hormones to make eggs. When fertility medications are
added Lupron allows the ovaries to grow multiple eggs and suppresses
the selection process that only permits one egg a month to ovulate. It
also prevents ovulation from occurring before the egg retrieval.

-------------------------------------------------


http://www.havingbabies.com/fertility-drugs-lupron.html
Lupron (leuprolide acetate)

-------------------------------------------------


http://www.advancedfertility.com/ivfstim.htm
Ovarian Stimulation for IVF

-------------------------------------------------


http://www.fertilitynetwork.com/articles/articles-ivf.htm
In Vitro Fertilization (IVF)

-------------------------------------------------


http://www.rxlist.com/cgi/generic/leuprolide_wcp.htm
LUPRON (leuprolide acetate)

Pregnancy, Teratogenic Effects: Pregnancy Category X. (see
CONTRAINDICATIONS section). When administered on day 6 of pregnancy at
test dosages of 0.00024, 0.0024, and 0.024 mg/kg (1/600 to 1/6 the
human dose) to rabbits, LUPRON produced a dose-related increase in
major fetal abnormalities. Similar studies in rats failed to
demonstrate an increase in major fetal malformations. There was
increased fetal mortality and decreased fetal weights with the two
higher doses of LUPRON in rabbits and with the highest dose in rats.
The effects on fetal mortality are expected consequences of the
alterations in hormonal levels brought about by this drug. Therefore,
the possibility exists that spontaneous abortion may occur if the drug
is administered during pregnancy. If this drug is administered during
pregnancy or if the patient becomes pregnant while taking any
formulation of LUPRON, the patient should be apprised of the potential
hazard to the fetus.

-------------------------------------------------


http://www.drugs.com/lupron.html
Lupron
leuprolide (LOO pro lide)
Eligard, Lupron, Viadur

What is Lupron?
 -- Lupron is related to a naturally occurring hormone called
gonadotropin-releasing hormone (GnRH). GnRH influences the release of
the hormones testosterone and estrogen in the body.
 -- Lupron is used to reduce the amount of testosterone or estrogen in
the body. It is used for conditions such as cancer of the prostate,
endometriosis (growth of uterine lining outside of the womb), uterine
fibroids, and early puberty (before 8 years of age in females and 9
years of age in males).
 -- Lupron may also be used for purposes other than those listed in
this medication guide.

What should I discuss with my healthcare provider before using Lupron?
 -- Lupron is in the FDA pregnancy category X. This means that Lupron
is known to cause birth defects in an unborn baby. Do not use this
medication if you are pregnant or could become pregnant during
treatment.

-------------------------------------------------


http://www.fda.gov/cder/foi/nda/2001/20-011S021_Lupron.htm
Lupron Depot (Leuprolide Acetate)
Company:  TAP Pharmaceuticals Products, Inc.
Application No.:  20-011/S021
Approval Date: 9/21/01

-------------------------------------------------


http://www.medicinenet.com/leuprolide/article.htm

PREGNANCY: Leuprolide should not be administered to pregnant women
because there is a high chance of harm to the fetus.


===============================================================
PRECAUTIONS FOR MAINTAINING INTRAUTERINE PREGNANCY AFTER AGE 40
===============================================================

http://www.send2press.com/newswire/2005-08-0831-008.shtml
One Last Chance for Pregnancy: A Review of 2,705 In Vitro
Fertilization Cycles Initiated in Women Age 40 Years and Above
Published: Wed, 31 Aug 2005, 04:56 EDT

HOFFMAN ESTATES, Ill. - August 31 (SEND2PRESS NEWSWIRE) -- Karande &
Associates today announces the recently published article by Sigal
Klipstein, MD in Fertility and Sterility entitled: "One last chance
for pregnancy: a review of 2,705 in vitro fertilization cycles
initiated in women age 40 years and above." This investigation is the
largest and most detailed ever published to look at fertility success
rates within this population.

The study shows that, as women are waiting longer and longer to
attempt pregnancy, they face a significant risk of infertility. While
pregnancy rates in women aged 40-43 remain reasonable, success drops
precipitously from age 44 years and on. By the end of the 45th year,
there are virtually no in vitro fertilization pregnancies.

-------------------------------------------------


http://www.karandeivf.com/Over40.pdf
http://www.karandeivf.com/Over40_PressRelease.pdf
August 2005 
One last chance for pregnancy: a review of 2,705 in vitro
fertilization cycles initiated in women age 40 years and above.
Sigal Klipstein, MD

Full length article (PDF) | WebMD review by Salynn Boyles | Press release (PDF)

***** The full-length article is 11 pages and includes full details
illustrated with tables and graphs.

-------------------------------------------------


http://my.webmd.com/content/article/110/109758.htm
After Age 44, Fertility Successes Are Few 
High-Tech Infertility Rx 'Reasonable' Until Mid-40s 
By Salynn Boyles
WebMD Medical News 

-------------------------------------------------


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16084887&dopt=Citation
Fertil Steril. 2005 Aug;84(2):435-45.
One last chance for pregnancy: a review of 2,705 in vitro
fertilization cycles initiated in women age 40 years and above.
Klipstein S, Regan M, Ryley DA, Goldman MB, Alper MM, Reindollar RH.
Boston IVF, Waltham, Massachusetts, USA. sklipstein@karandeivf.com

OBJECTIVE: To describe live birth rates and predictors of success in
1-year age increments for women > or =40 years when initiating
assisted reproductive technologies (ART).
DESIGN: Retrospective database analysis. 
SETTING: A large university-affiliated infertility center. 
PATIENT(S): One thousand two hundred sixty-three women undergoing
2,705 ART cycles at age 40 or above.
INTERVENTION(S): Couples undergoing ART. 
MAIN OUTCOME MEASURE(S): Pregnancy and live birth rates per cycle
start were determined based on 1-year increments in women aged > or
=40. Predictors of success, including number of embryos transferred,
number of fetal heartbeats, availability of embryos for
cryopreservation, and cycle day 3 FSH levels, were analyzed.
RESULT(S): The overall live birth rate per cycle start was 9.7%.
Cumulative live birth rates in women ranged from 28.4% if starting ART
at age 40 to 0 by age 46. The overall spontaneous abortion rate was
32.6% (range, 23.9%-66.7%). Higher pregnancy rates were predicted by
the greater number of embryos available for transfer, by the
availability of excess embryos for cryopreservation, and by the
presence of two fetal heartbeats on ultrasound. The outcome of the
first IVF cycle did not predict the outcome of subsequent cycles.
CONCLUSION(S): Assisted reproductive technology has a reasonable
chance for success (>5%) up until the end of the forty-third year.
Twins on initial ultrasound, large numbers of embryos available for
transfer, and the presence of excess embryos for cryopreservation
predict higher live birth rates.

PMID: 16084887 [PubMed - in process]

-------------------------------------------------


http://www.fertilityneighborhood.com/content/in_the_news/archive_1263.aspx
Is There Still Hope After 40?
08-24-05

In what's being touted as the largest study to date of assisted
reproductive success in women over 40, doctors have concluded there's
still a "reasonable" chance of success in their efforts to achieve a
pregnancy.1

"The biggest obstacle most women over 40 face is two-fold: diminishing
ovarian reserve coupled with poor embryo quality," explained the
study's first author, reproductive endocrinologist Sigal Klipstein,
MD, who practices at Karande & Associates, a fertility clinic near
Chicago.  This in turn, boosts the risk of miscarriage, the
investigators pointed out.

Examining ART Results
But the research team wanted to know if those challenging prospects
should preclude women over age 40 from undergoing assisted
reproductive technologies (ART). To better clarify this, the
investigators pulled patient records related to more than 2,700 cycles
involving women over 40 using in vitro fertilization (IVF) and/or
intracytoplasmic sperm injection (ICSI) between 1999 and 2002. The
team performed a second analysis, pulling records of a smaller group
of patients whose first IVF or ICSI occurred after age 40, during the
same period. This was done to determine any differences in outcome
between women who started using assisted reproductive technologies
(ART) before age 40, then continued past their 40th birthday, and
those who began ART for the first time in their 40s.

While pregnancy rates weren't much different in those aged 41 through
43, the number of successful outcomes dropped off significantly
starting with women aged 44 and above. In those aged 45, only one
healthy birth resulted, and no births occurred in women beyond that
age.

By comparison, in the smaller group of women who began ART for the
first time after age 40, the trend was the same. About 28 percent of
those aged 40 gave birth (73 of 257 women), but that number slowly
declined with age. By age 44, only one in 62 women had successfully
given birth. Successful outcomes weren't much different for those aged
40 through 42, but were significantly lower in older women.

Setting the Record Straight
Otherwise, "reasonable" success using ART can be expected for women in
their early 40s, they concluded. "Although rare pregnancies will occur
at age 44 years and beyond, women in this age group should be strongly
advised to consider other options, including egg donation and
adoption, as the rates of success quickly fall from below 3% per cycle
at age 44 years, to well below 1% within 1 to 2 years," the
researchers wrote.

-------------------------------------------------


http://cumc.columbia.edu/dept/obgyn/rightbar/newsletters/summer02.html
The Center for Women?s Reproductive Care at Columbia University

What are the success rates for women over 40?
Birth after 40 is rare, but receives much press. You may be surprised
to learn that just 2% of babies born each year in the U.S. are born to
women over 40. And 75% of these are born to 40-year-olds.

Why is it so difficult to conceive at 40 or 45?
Difficulty is normal when trying to conceive after 40. The main
obstacle is the biology of the human egg. Most eggs retrieved for IVF
after 40 are abnormal and don?t lead to pregnancy.

How much does IVF improve success rates?
IVF dramatically improves your chances after 40. Women who are
infertile at age 40 have a less than 1% chance of spontaneous
conception each month. But they achieve a birth following embryo
transfer 15% of the time. Using donated eggs from younger women
improves this success rate to roughly 50%.

What?s the upper age limit for donor egg treatment?
Women up to age 55 can get pregnant at the same rate as younger women
using donated eggs. After age 45, patients undergo screening for high
risk factors.

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http://health.yahoo.com/ency/healthwise/hw227379
In vitro fertilization for infertility
How Well It Works

The number of women who give birth to a live infant after in vitro
fertilization varies depending on the cause of infertility. The
average success rate for IVF is about 25%. 1 However, IVF success
varies widely depending mostly on the woman's age, the cause of the
couple's infertility, and pregnancy history.

The aging of the egg supply has a powerful effect on the chances that
an assisted reproductive technology (ART) procedure will result in
pregnancy and a healthy baby. Many women over age 40 choose to use
donor eggs, which greatly improves their chances of giving birth to a
healthy child.

Age. Per year, birth rates resulting from embryo transfer using
women's own eggs are about: 2
35% for women age 34 and younger. 
28% for women age 35 to 37. 
20% for women age 38 to 40. 
10% for women age 41 to 42. 
4% for women 43 and older. 

Own eggs versus donor eggs. Birth rates are affected by whether ART
procedures use a woman's own eggs or donor eggs. Per embryo transfer:
2

Using her own eggs, a woman's chances of having a live birth decline
from about 40% in her late 20s, to about 30% at age 37, to about 10%
by age 42.

Live birth rates are the same among younger and older women using
donor eggs. At age 30 and at age 45, the average donor egg birth rate
using fresh (not frozen) embryos is 47%.

Frozen IVF embryos that are thawed and transferred to the uterus are
less likely to result in a live birth (average 23% success) than are
newly fertilized IVF embryos (average 33% success). However, frozen
embryos are less expensive and less invasive for a woman, because
superovulation and egg retrieval aren't necessary. 2

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http://www.hypertension-consult.com/Secure/textbookarticles/Primary_Care_Book/113.htm
Ectopic Pregnancy: Part II

Spontaneous Miscarriage
Up to 20% of pregnant women will experience vaginal bleeding during
the first weeks of pregnancy, and as many as 50% of them will progress
to miscarriage.35 The risk of miscarriage varies greatly with age. For
patients younger than 20 years, the risk averages only 12%, whereas in
patients older than 45 years it approaches 50%.36

Pathophysiology. 
Spontaneous miscarriage may result from abnormal embryo development or
from maternal factors. Up to 50% of women with spotting or cramping
early in pregnancy will have an abnormal intrauterine pregnancy on
initial ultrasound, with many of these embryos being morphologically
abnormal.39 Approximately 33% of miscarried specimens lost before 9
weeks are due to anembryonic development, termed a ?blighted ovum.?40
In this case, only an empty gestational sac is seen on ultrasound.

The significant percentage of embryonic abnormalities represents a
natural process that eliminates almost 95% of cytogenetic defects
before birth. The rate of identified chromosome defects in miscarried
embryos from the first trimester approaches 60%, and falls to 7% by
the end of the 24th week.34

Threatened Miscarriage
Up to 95% of pregnancies will continue to live birth if a normal fetal
heart rate is found at 8 weeks gestation.46 The rate of pregnancy loss
is only 1% when a live fetus is present at 14-16 weeks gestation.44 To
date there is no convincing evidence that any treatment will change
the outcome in patients diagnosed with threatened miscarriage.

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http://www.extenza-eps.com/RCOG/doi/full/10.1576/toag.2002.4.3.124?cookieSet=1
Complications of assisted reproduction

EARLY PREGNANCY LOSS
Miscarriage
Several authors have concluded that the incidence of miscarriage is
higher with IVF pregnancies than natural conceptions. ? The fact that
miscarriage rates in IVF pregnancies are high, regardless of the cause
of infertility, suggests a possible relationship to gonadotrophin
therapy or multiple ovulation. ? Therefore, the apparent increase in
miscarriage associated with IVF appears to be multifactorial with
infertility itself, regardless of cause, being of major
significance.30

Ectopic pregnancy
The ectopic pregnancy rate varies between 2?11% in reported series of
IVF pregnancies.31 Ectopic pregnancy rates in the general population
are around 2.5%. The aetiology of ectopic pregnancy after IVF and
embryo transfer is multifactorial with tubal disease being the main
factor. Damaged tubes, unlike normal tubes, may not be able to propel
an embryo that has migrated into the tube back into the uterine
cavity.32 Reverse migration of the embryos may also be associated with
the high concentration of oestradiol or an altered oestrogen:
progesterone ratio.33 In addition to numbers of embryos transferred
the technique of embryo transfer may contribute to the increased risk
of ectopic pregnancy, by forcing the embryos through the tubal ostia
by hydrostatic pressure.34 This could arise if a large volume of
transfer fluid is used or if the embryo transfer catheter was placed
either beyond the mid-cavity of the uterus or into the tube itself.
Heterotopic pregnancy is estimated to occur in 1% of IVF pregnancies
compared with an incidence of 1 in 3889?4778 spontaneous
conceptions.35

OBSTETRIC OUTCOME
Women who become pregnant after IVF or GIFT are at increased risk of
multiple pregnancy, preterm labour, low infant birthweight and
perinatal death.28,37,38, However, of these the major complication is
multiple pregnancy.

Dhont et al47 reported that the perinatal mortality rate in assisted
reproduction singleton pregnancies, even when matched for age, parity
and fetal sex, was more than twice that in control pregnancies (13.4%
vs 5.9%). The incidence of congenital malformations was also
significantly higher (3.1% vs 1.7% in the general population). This
may, however, reflect the older age of women who conceive with IVF as
the difference was lost after matching for age.

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8828432&dopt=Abstract
Am J Obstet Gynecol. 1996 Sep;175(3 Pt 1):668-74.
Very advanced maternal age: pregnancy after age 45.

OBJECTIVE: Our purpose was to describe the maternal and fetal outcomes
of pregnancies in women > or = 45 years old at delivery.
STUDY DESIGN: A retrospective review of in-hospital deliveries after
20 weeks of gestation was performed in four Utah tertiary care
hospitals for the 10-year period between 1985 and 1994.
RESULTS: Seventy-nine cases were identified among 126,500 births, with
an incidence of 0.63 per 1000 births. Maternal ages were 45 (n = 44),
46 (n = 21), and > or = 47 (n = 14) years. Three of the conceptions
were assisted, including both twin gestations. Thirty-seven (46.8%)
had obstetric complications during pregnancy; the most frequent
complications were gestational diabetes (12.7%) and preeclampsia
(10.1%). Median (range) gestational age at delivery was 39 (22.9 to
41.7) weeks; 12 (15.2%) deliveries occurred before 37 weeks. Eight
(9.9%) karyotype abnormalities were diagnosed. The cesarean section
rate was 31.7%; the most frequent indications were abnormal lie (n =
9), fetal distress (n = 5), and previous cesarean delivery (n = 5).
There were no maternal deaths. Median (range) birth weight was 3466
(397 to 5085) gm; 14 (17.3%) were < 2500 gm and 16 (19.8%) were > 4000
gm. Twelve (14.8%) infants were admitted to the neonatal intensive
care unit. The corrected perinatal mortality rate was 1.3% (1/78).
CONCLUSIONS: In women > 45 years old at delivery maternal and fetal
outcomes were generally good, but there was a high incidence of
pregestational (chronic hypertension, hypothyroidism) and gestational
(karyotype abnormalities, gestational diabetes, cesarean section,
macrosomia) complications. This information may be helpful for
counseling women between 45 and 50 years old who are considering
pregnancy.

PMID: 8828432 [PubMed - indexed for MEDLINE]

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http://www.marchofdimes.com/professionals/681_1155.asp
Pregnancy After 35

What is the risk of birth defects in babies of women over 35?
The risk of bearing a child with certain chromosomal disorders
increases as a woman ages. The most common of these disorders is Down
syndrome, a combination of mental retardation and physical
abnormalities caused by the presence of an extra chromosome 21 (humans
have 23 pairs of chromosomes). At age 25, a woman has about a
1-in-1,250 chance of having a baby with Down syndrome; at age 30, a
1-in-1,000 chance; at age 35, a 1-in-400 chance; at age 40, a 1-in-100
chance; and at 45, a 1-in-30 chance.

What is the risk of miscarriage as a woman gets older?
Most miscarriages occur in the first trimester for women of all ages.
The rate of miscarriage in older women is significantly greater than
that in younger women. A 2000 Danish study found that about 9 percent
of recognized pregnancies for women aged 20 to 24 ended in
miscarriage. The risk rose to about 20 percent at age 35 to 39, and
more than 50 percent by age 42. The increased incidence of chromosomal
abnormalities contributes to the agerelated risk of miscarriage.

Does the risk of pregnancy complications and adverse pregnancy
outcomes increase after age 35?
While women in their late 30s and 40s are likely to have a healthy
baby, they do face more complications along the way.


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SEARCH STRATEGY
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concurrent ectopic uterine pregnancy 
Heterotopic pregnancy
heterotopic pregnancy rate 
heterotopic pregnancy successful birth
heterotopic pregnancy survival rate intrauterine 
ivf after age 45
pregnancy after 45