Results of preoperative investigations and IVF
The human leukocyte antigen (HLA) mismatch was 1/0, and insignificant anti-HLA antibodies existed but no donor-specific antibodies were detected. Donor and recipient were both seropositive for cytomegalovirus (CMV) and Epstein-Barr virus (EBV).
Examination of donor uterus by TVU showed a normal-sized uterus with a 20 mm subserosal fibroid. The MRI of the donor uterus showed a 7 x 7-mm polyp in the bladder, and she underwent cystoscopy with excision of the polyp. The microscopic examination showed benign inflammatory pseudotumor.
Selective angiography of the uterine arteries showed visible and contrast-enhanced uterine arteries on both sides with a diameter of the lumen of the right and left uterine artery of 2.9–4.4 mm and 3.5–3.9 mm, respectively. Preoperative MRI imaging of the recipient showed a uterine rudiment measuring about 15 x 30 mm; normal ovaries bilaterally, sized 20 × 30 mm; and normal kidneys with normal size, shape, and positions.
Recipient serum level of anti-müllerian hormone (AMH) was 4.2 μg/L. The partner’s semen sample was normal (semen volume was 4 ml, total sperm count in ejaculate was 160 million/ejaculate, sperm concentration was 40 million/ml, total motility was 60%, progressive motility was 40%, non-progressive motility was 20%, and non-motile was 20%). Thirteen oocytes were collected in a single stimulation cycle, 11 were mature (M2), and eight grew to blastocyst stage and were cryopreserved.
Surgery—donor
Donor surgery lasted for 608 min, and estimated blood loss (EBL) was 900 ml. Recovery was complicated by lung atelectasis and increased level of c-reactive protein (CRP) 62 mg/L without fever. It was successfully treated with piperacillin/tazobactam i.v. for 6 days. Length of hospital stay for the donor was 7 days. Anti-thrombotic prophylaxis with low molecular weight heparin (LMWH) Lovenox 4000 IU was initiated on preoperative day 1 and continued for 4 weeks after the surgery. After discharge from the hospital, she was healthy and did not present with any symptoms.
One month after the surgery, she underwent a duplex Doppler ultrasound scan of both lower limb veins with no evidence of any deep vein thrombosis and competent sapheno-femoral junctions on both sides. The urinary tract ultrasound showed a normal urinary tract with normal-sized kidneys on both sides.
Surgery—recipient
Total ischemic time on the back-table was 85 min. Surgical time of the recipient was 363 min (including the anastomosis time 105 min), and EBL was 700 ml. The blood flow of the uterine arteries on both sides was measured before the abdomen was closed. The perioperatively measured (Doppler) blood flow of the uterine artery was 45 ml/min and 46 ml/min on the right and left uterine artery, respectively. The hospital stay was 7 days. No episode of inflammation or rejection has been diagnosed until today. Anti-thrombotic prophylaxis with low molecular weight heparin (LMWH) Lovenox 4000 IU was initiated on preoperative day 1 and continued for 4 weeks after the surgery. She was also treated with 81 mg acetyl salicylic acid (ASA) daily. Two and 4 weeks after UTx, the vaginal culture and urine culture were positive with Enterococcus faecalis and Enterobacter plus Klebsiella pneumoniae, respectively. She was treated with oral antibiotics (levofloxacin 500 mg once a day for 5 days and amoxicillin and clavulanate 1 g twice a day for 7 days) both times with good results. Repeated cultures were normal thereafter.
The first menstrual bleeding occurred 3 weeks after UTx, and menstruations were then regular every 28 to 30 days. The patient developed stenosis over the vaginal-vaginal anastomosis, which tightened gradually after surgery and required manual dilations under sedation three times. Due to persistent anemia, the patient was given erythropoietin 2 times a week 4000 IU s.c. and oral ferrous sulfate with vitamin B12 3 months before embryo transfer due to hemoglobin levels decreasing from 130 g/L before UTx to 95 g/L post UTx and further down to median 77 (77–88) g/L before the treatment. Afterwards, the hemoglobin increased to median level of 95 (88–100) g/L, remained stable during the pregnancy, and declined to 88 g/L at delivery.
Embryo transfer
Ten months after UTx, embryo transfer was performed. A single dose of triptorelin 3 mg was given 7 days before a predicted menstruation. Endometrial thickness of 8.5 mm with triple layers was achieved with a daily administration of estradiol hemihydrate 4 mg per day for 10 days. Embryo transfer was carried out after progesterone supplementation (progesterone in oil 25 mg daily, i.m., and vaginal micronized progesterone 100 mg twice daily) for 6 days. One blastocyst was transferred under abdominal ultrasound guidance. It resulted in a pregnancy confirmed with a positive pregnancy test 14 days after blastocyst transfer. Four weeks later, a viable pregnancy with fetal heartbeat was
Pregnancy
Immunosuppression therapy remained unchanged and consisted of tacrolimus and azathioprine as described above. The concentrations (median (range)) of tacrolimus during pregnancy were 5.5 (3.4–7.9) ng/mL. During the first trimester, anticoagulation prophylaxis consisted of low molecular weight heparin (LMWH) Lovenox 4000 IU once a day and acetyl salicylic acid 81 mg daily which was increased to 160 mg daily from week 12. Progesterone supplementation, both intramuscular injections of progesterone in oil and vaginal micronized progesterone, was gradually tapered by the end of the first trimester. Estradiol 2 mg p.o. once a day was also given during the first trimester. Creatinine levels (median (range)) were normal, with 54.5 (44.2–62.1 μmol/L during the whole pregnancy. Hemoglobin levels (median (range)) were normal to low, with 95 g/L (88–100 g/L) and decreased to 88 g/L at delivery. Hemoglobin increased gradually to 116 (114–118 g/L) after delivery. There were no signs of preeclampsia with normal blood pressure and no significant proteinuria for the duration of pregnancy.
The fetal growth of biparietal diameter, abdominal diameter, femur length, and estimated weight were within the normal range throughout pregnancy as shown in Fig. 1. The pulsatility index (PI) of the umbilical artery and uterine arteries was low to normal, with median PIs of 1.06 (0.7–1.85) and 0.71 (0.7–0.72), of umbilical artery and uterine arteries, respectively.
Cervical length measured on TVU was stable throughout pregnancy with a median length of 30 mm. Cervical biopsies were taken at 16 and 28 weeks. Histology showed no signs of rejection. The patient had minor vaginal bleeding during the 9th week of pregnancy, which led to temporary discontinuation of ASA for 6 days.
The total weight gain was 15 kg. Patient reported perception of fetal movements. Cesarean section was performed at 35 weeks and 1 day due to premature contractions registered on cardiotocography (CTG), and with shortened cervix to 15 mm and dilated at 15 mm. The cesarean section was performed under spinal anesthesia through a midline incision in the abdominal wall and midline incision into the uterus due to big veins in the lower transverse area. The cephalically positioned female fetus was delivered 15 min after skin incision. Apgar score was 9-10-10. Umbilical artery pH was within normal range. Placenta was normal on visual inspection, weighted 472 g and of normal histology. The baby’s weight was 2620 g (within the normal range for the gestational age), and she was 47 cm long (Fig. 2). The total surgery time was 45 min.
No neonatal intensive care was required. The mother and child were discharged from the hospital after 4 days, and breastfeeding was established and continued for 1 month until the patient decided to wean. The baby developed bronchiolitis at the age of 3 weeks and was hospitalized in a neonatal intensive care unit for 2 weeks. Treatment was with i.v. antibiotics and chest physiotherapy. Later development was normal during the 6 months observation, and the weight at 6 months was 7150 g.
Currently, the patient remains on unchanged immunosuppression regime and will undergo another embryo transfer in the upcoming months.