A
55 years old lady, para 1 with no living issue was desperate to have her own
baby. Despite extensive counselling regarding the risk to her life, the
complications that could arise during pregnancy, and the problems of bringing
up a baby later, she was not willing for surrogacy or adoption. The social
stigma attached to infertility in India was probably the reason she was not
willing for anyother option.
She
was postmenopausal for the last 8 years and had no history of postmenopausal
bleeding. There were no other medical problems which would otherwise
contraindicate pregnancy. She was married since 35years. She spontaneously
conceived a year after her marriage. It was an uneventful pregnacy till 30weeks
when she had PPROM and delivered a preterm baby at home. The baby expired an hour
after birth. She had secondary infertility. She complained of heavy periods and
was diagnosed to have fibroids and underwent myomectomy at a private nursing
home 25 years back. Since then, her periods were scanty until her menopause.On
examination, there was a vertical midline infraumbilical scar. An ultasound examination revealed a 3 x 3 cm
fibroid on posterior wall of uterus.
A
hysteroscopy was planned. On hysteroscopy, there were grade 3 adhesions. Hysteroscopic
adhesiolysis was done under general anaesthesia. Cyclic estrogen and
progesterone was started for 3months. A relook hysteroscopy was done which
showed adequate cavity and minimal adhesions at the fundus. Consent for embryodonation was obtained as
her husband was azoospermic. After giving her a cyclic estrogen and
progesterone for inducing withdrawl bleed, we started her on oral estradiol 2mg
per day for three times a day. On day 8, her endometrial thickness on a
transvaginal scan was 4mm and not well defined. The dose was increased to
estradiol 12mg per day, but ET on day 12 was still the same. Vaginal
siladenafil 25mg four times a day was added. The day 14, ET was 5mm and not
well defined. Her cycle was cancelled. In
the next cycle, she was given the same dose of estradiol, but siladenafil was
addded earlier on day 7. However, the ET was 5mm and illdefined. She was
counselled for surrogacy, but refused to agree.
Intrauterine
G-CSF use to improve endometrial thickness was thought as the next step. A
fully informed, detailed consent of the off-label use of G-CSF, the lack of knowledge
about the possible side-effects to the mother and the fetus were explained to
the couple.
In
the next cycle, besides the dose of estradiol and siladenafil, intauterine
G-CSF 0.5ml was instilled with the
intrauterine insemination cannula under ultrasound guidance on day 7. Her ET on
day 10 was 5.6 mm, but not well defined. A repeat instillation was done the
same day and a day 13 ET was 6.2mm, illdefined. A third instillation of G-CSF
was done. Her day 15, ET was 7mm and still illdefined. Progesterone in the form
of intramuscular injection was added on day 15 and day 16. A day 2 transfer was
done on day 17. Luteal support with progesterone was continued. On day 14, her β-hcg
was 1013IU/l. An ultrasound done 2 weeks
later showed twin gestational sac. She had bleeding at 7 weeks, was given
injectable progesterone and bleeding stopped. Pregnancy continued uneventfully.
Her blood pressure at 14weeks was 140/100mm Hg on two occasions. She was
started on alphamethyldopa 250mg three tines a day which was later increase to
500mg four times a day and labetolol was added at 20 weeks. The level II scan
was normal except for placenta anterior and reachng os. At 26 weeks, she complained of breathlessness
and diagnosed to have heart failure. She was referred to a tertiary level
hospital where she was admitted in the Intensive Care Unit. A cardiologist
referral was done. Fetal monitoring was done. At 30 weeks, she developed severe
pre-eclampsia and her blood pressure was 200/120mmg with proteinuria of 3+. She
was taken up for an emegency Lower segment Caesarean Section with a high risk
consent. Both babies were delivered by breech extraction. The first baby was 1300mg
and the second baby was 800gms. At the time of removal of placenta, she was
discovered to have placenta percreta for which a hysterectomy was done. She
received 2 units of blood transfusion.
Her post operative course was uneventful. The second baby expired a week
after birth because of sepsis. The first baby was kept in the NICU for 2 weeks.
Presently the baby is 2.2 kg and is healthy. The lady is doing well on
antihypertensives.
Discussion
This
case teaches us many lessons. First, pregnancy in a 55 year old lady could be
life threatening. Second, a childless women in India suffers ostracism, stigma
and so much discrimination that she is driven to take extreme steps and even risk
her life to get a child.
Third,
in a women with resistant thin endometrium, intrauterine G-CSF could be an
option, although it has to be proved by larger studies. G-CSF has many roles in
human reproduction. It is present in follicular fluid, plays role in ovulation1
as well as in implantation2. It has been studied in recurrent
implantation failure, in poor responders 3and in repeated pregnancy
losses4.
The
role of G-CSF in resistant thin endometrium has been studied in a case series
of four women.5 All four women did not respond to maximum dose of
estrogen and vasodilators in an IVF cycle and were given a single dose of
intauterine G-CSF. In all the four women, the endometrial thickness improved to
7mm and all of them conceived.
Similar
to this study, the result in our case was absolutely unexpected and a miracle
to us and the lady, because despite giving her three doses of G-CSF in contrast
with just a single dose in the above study, her endometrial thickness did
improve but was not a triple layer pattern and was never clearly discernible.
Hence, besides the proliferative action of G-CSF on the endometrium, it has
probably an action on blood flow or other parameters, thereby leading to better
implantation. Both the effects, however need to be confirmed by larger well
designed, double blinded studies and the safety seems to be established, before
drawing any conclusion. In addition, the effects of G-CSF needs to be
elucidated at a molecular level. If this is proved, it will be a breakthrough
for these few yet important group of women with thin endometrium who do not
respond to anything.
And
the last lesson to be learnt is as said by Patricia Neal that “a strong positive mental attitude will create more
miracles than any wonder drug”.
Dr. Priti Gupta is the Senior Consultant in Fertility & IVF
Specialist in Delhi. She is trained and worked at the Best IVF Center in West Delhi, which is quite prominent
& popular in west Delhi.
