A 37 year-old Caucasian nulligravida and her husband presented for evaluation of primary infertility of approximately one year duration. Both were in good general health and neither were smokers. A normal Pap teat was obtained eight months before presentation, and there was no history of any prior cervical cytology abnormality. The provisional diagnosis of cervical stenosis had been made based on an abnormal hysterosalpingogram (HSG) performed approximately six months before referral. Although the radiograph was technically difficult because of the inability to pass the catheter fully through the cervical canal, the study was able to show a pronounced filling defect near the area of the internal cervical os (Figure ). Fallopian tubes were patent bilaterally, and free intraperitoneal spill without peritubal loculation was documented.
Figure 1 Early fill view from hysterosalpingogram obtained from our patient with severe cervical stenosis (arrow). Extensive cervical stricture prohibited passage of insemination or embryo transfer catheters; safe transcervical instrumentation was also impossible. (more ...)
Ovarian reserve was estimated as reported previously [1
], with cycle day #2 serum FSH and E2
measured at 7.0 mIu/ml and <32 pg/ml, respectively. All other laboratory tests were within normal limits. Andrology evaluation consisted of a semen analysis, which showed total spermatozoa concentration of 70.5 M/ml, 60% forward progression motility, and 17% normal forms morphology (1999 WHO criteria). A previous urology consultation had identified a varicocele, which was repaired without complication approximately one month before the couple presented at our center. Four months post-varicocelectomy, repeat semen analysis found total spermatozoa concentration to be 46 M/ml, 70% forward progression motility, and 3% normal forms morphology (Kruger strict criteria).
The couple elected to undergo ovulation induction followed by IUI, with the understanding that should such therapy fail, IVF with intracytoplasmic sperm injection (ICSI) would be considered [2
]. Prior to either therapy however, hysteroscopy was recommended to map cervical anatomy with greater precision. Therefore, about one month after presentation, assessment of cervical and endometrial contours was attempted under general anesthesia, via 3 mm hysteroscope. However, due to extensive cervical fibrosis, instrumentation proximal to the internal cervical os was impossible and hysteroscopy was abandoned.
The defect identified at surgery was consistent with the stricture suggested on HSG, which appeared as a "D"-shaped protrusion into the cervical canal. When the patient was informed of the operative findings, she essentially decompensated and expressed suicidal ideation. The planned outpatient procedure was therefore modified to include a brief hospital stay to facilitate psychiatry consultation and formal mental status examination. She was discharged home in stable condition 14 h after hysteroscopy following psychiatric clearance for continued fertility therapy.
Follow-up consultation two weeks post-hysteroscopy included discussion of controlled ovarian hyperstimulation with gamete intrafallopian transfer [3
]. IVF+ICSI, followed either by tubal embryo transfer [4
] or transmyometrial embryo transfer [5
] was also contemplated, as was ovulation induction with direct intraperitoneal insemination (IPI). After evaluating the risks and benefits of such therapies, the couple elected the latter option. An initial ovulation induction treatment with IPI occurred two months after the aborted hysteroscopy, but the patient did not conceive. The following month, the patient underwent a second gonadotropin ovulation induction sequence using 150 IU/d recombinant FSH (Gonal-F®
, Serono Laboratories; Norwell, Massachusetts USA) plus 150 IU/d human menopausal gonadotropin (Repronex®
, Ferring Pharmaceuticals; Copenhagen, Denmark), both administered subcutaneously [6
]. After a six day follicular recruitment phase, there were 3 follicles with mean diameter >16 mm. Terminal serum estradiol was ~1200 pg/ml, and a 12 mm trilaminar endometrium was noted. Nonrecombinant hCG (10,000 IU; Novarel®
, Ferring) was administered subcutaneously when serum estradiol and transvaginal sonography suggested follicular maturity [7
The patient returned 24 h after hCG injection, where informed consent was again obtained for direct IPI under real-time transvaginal sonographic guidance. On the day of insemination, the partner's semen parameters were 70 M/ml with 60% motile cells (morphology analysis not performed). The specimen was washed twice with human tubal fluid, and then layered upon a dual-density (90%/45%) gradient (PureSperm®
, Nidacon International; Gothenburg, Sweden) and centrifuged at 300 g
]. Resuspended to a volume of 10 ml, the sample was then divided into two components of 5 ml each. These two equivalent samples were injected directly into the intraperitoneal cavity (5 ml to each tubal fimbria). IPI was accomplished by 17 gage single-lumen oocyte retrieval needle (Cook IVF; Spencer, Indiana USA) passed under transvaginal sonographic guidance. No intravenous sedation was administered, but each vaginal fornix was pretreated with 1% lidocaine without epinephrine (AstraZenica Pharmaceuticals LP; Wilmington, Delaware USA) via 25 gage spinal needle. After transvaginal mucosal puncture, the proximal vagina was reexamined and good hemostasis was noted. She tolerated the procedure well and there were no complications. Luteal support commenced the day after IPI, following a 400 mg/d transmucosal protocol as described previously [9
The patient had no menses two weeks post-procedure; she returned for pregnancy test and a serum hCG of 223 mIU/ml was registered. Two days later, the value had increased to 411 mIU/ml. One month after insemination, transvaginal sonogram revealed a single intrauterine gestational sac with mean diameter of 15 mm (5 6/7 weeks gestation). A 5 mm fetal pole (6 0/7 weeks gestation) was also seen, with embryonic cardiac activity documented by B-mode Doppler pulse sonography (rate = 124/min). The intrapartum course remains uncomplicated through the 20th gestational week.