A 21 year-old Caucasian nulligravida presented with her partner for assessment and treatment of primary male factor infertility of 24 months duration. Both were in good general health and the female's past gynecological history was unremarkable. The wife smoked approximately 1/2 pack of cigarettes daily, and used alcohol only rarely. Her only regular medication was a prenatal vitamin. Physical exam revealed no abnormality; BMI was 20 kg/m2. Her blood type was O positive. Cervical cytology and laboratory tests results were all normal, and saline hysterography identified no intracavitary defects. The patient had never used ovulation induction agents or periovulatory hCG.
The partner was a non-smoker and took no regular medications. He had commissioned no pregnancies in a prior marriage, and had been diagnosed with azoospermia four years earlier. Urological evaluation found no anatomical abnormality. Karyotype was normal 46, XY and Y-chromosome microdeletion analysis via polymerase chain reaction method was negative for any known mutation. Obstructive azoospermia (rete testes obliteration) had been diagnosed after exploratory scrotal surgery four years before presentation. The couple declined intrauterine insemination with anonymous donor sperm for personal reasons. Given the male factor infertility diagnosis necessitating intracytoplasmic injection (ICSI), the couple elected in vitro fertilization utilizing surgically retrieved spermatozoa. Full informed consent was obtained, including a discussion of multiple gestation risk.
Following pituitary downregulation with intranasal nafarelin acetate (0.4 mg/d), controlled ovarian hyperstimulation commenced using a combined FSH+hMG protocol. Subcutaneous hCG was administered on stimulation day 11, when serum estradiol was 2110 pg/ml. Twenty-two oocytes were retrieved via ultrasound-guided transvaginal needle aspiration, undertaken in parallel with spermatozoa collection via testicular biopsy (both procedures performed under intravenous sedation). Utilizing ICSI, 10 oocytes advanced to the 2pn stage. Two embryos (8 and 9-cell stage) were transferred fresh on post-fertilization day three after assisted hatching via acid Tyrode's method. One blastocyst was cryopreserved. Serum hCG was 423 mIU/ml two weeks after embryo transfer.
Transvaginal 4 mHz sonogram (SDU400+, Shimadzu Corp; Kyoto, Japan) performed at eight weeks' gestation demonstrated a single 28 mm intrauterine gestational sac (chorion) with three distinct fetal poles, each with discrete cardiac activity. Amniotic membrane configuration could not be immediately determined. Follow-up transvaginal ultrasound one week later refined the diagnosis as monochorionic-triamniotic triplet pregnancy (Figure ). Total daily folic acid dose was increased to 1 mg/d, and antenatal care was co-managed with periodic perinatal consultation. The obstetrical course was uncomplicated until ~19th gestational week, when cervical funneling became evident via transvaginal sonogram. Based on this finding, the patient was admitted to hospital and a McDonald (rescue) cerclage was placed without difficulty. The post-operative course was uneventful and the patient was discharged home the next day.
Figure 1 Transvaginal sonogram image of intrauterine monochorionic-triamniotic triplet pregnancy at 9 weeks' gestational age, demonstrating three separate embryos, distinct amniotic membranes (A), and unified chorion (C). The conception resulted from a two-embryo (more ...)
At 28 weeks' gestation, the patient was readmitted to hospital for mild preeclampsia with a blood pressure of 140/80. To promote fetal lung maturity, betamethasone (12 mg × 2 doses) was administered via intramuscular injection. The patient had no focal neurological signs and ALT and AST were elevated (97 and 121 u/l, respectively). Liver function tests normalized soon after admission. Platelet count was 157,000 and protein (325 mg) was present in 24 h urine collection. Multifetal biophysical profiles were performed every 48 h with reassuring results. At 305/7 weeks' gestation, serum uric acid was 7.8 mg/dl, platelets had fallen to 115,000, and the patient began to experience visual scotomata. Based on these findings consistent with worsening preeclampsia, the patient underwent a primary low-transverse cesarean delivery (estimated blood loss = 1,000 ml) resulting in the births of three viable female infants (1475, 1021, and 1021 g); one vertex and two breech presentations. Apgar scores were and 8/9, 9/9, and 8/9, respectively. A single three-umbilical cord placenta (weight = 639 g) was delivered without complication, and each umbilical cord was morphologically normal. The patient was discharged home after seven days in good condition, and two of the triplets were discharged home three weeks later. The other infant was discharged home at eight weeks age due to necrotizing enterocolitis that required surgery for intestinal obstruction. At six months follow-up, mother and babies continue to do well.