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.
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.