2nd infertility and repeated implantation failure_2
Short Summary

41-year-old female who had been attempting to conceive for the past several years. She underwent several failed fertility treatment attempts, and conceived following a clomid /gonadotropin stimulation but it ended with miscarriage.  Following this she underwent five IVF/ intracytoplasmic sperm injection cycles without success.

Patient's Questions Medical Background

Patient is a 41-year-old female who had been attempting to conceive with her husband, for the past several years. The couple underwent several failed fertility treatment attempts, which included a total of five in vitro fertilization (IVF) treatments.
Patient’s past medical history is significant for mild pelvic endometriosis diagnosed during a laparoscopy performed in 2004. She was diagnosed with a cancerous skin mole, which was resected with clear margins in November 2005. 
Patient’s past surgical history consists of an appendectomy in 1987, a laparoscopy (endometriosis) in 2004, a curettage (D&C) procedure for a missed abortion in 2004, and several resections of a skin mole/lymph nodes in 2005. Patient underwent a screening colonoscopy in 2006 as her father passed away from colon cancer at age 47.
Patient’s work-up for infertility included routine lab work from 2002 which revealed unremarkable results for FSH, LH, testosterone, prolactin, TSH, and day 21 serum progesterone levels. No current lab work (day 3 FSH/estradiol) was available. Information regarding a hysterosalpingogram (HSG) or sonohysterogram (SHG) was not available.
Medical history provided for the husband was limited. It is my understanding that he is a 40-year-old smoker who suffers from no significant abnormalities in his semen analysis (mild teratospermia noted in a semen analysis from 2002).
Patient conceived following a clomid/gonadotropin stimulation in 2004 (miscarriage). Following this, the couple underwent five IVF/intracytoplasmic sperm injection (ICSI) cycles from April 2005 through May 2007, for which detailed medical information is only available for four cycles. In summary, each of the IVF/ICSI cycles was a standard long protocol with Buserelin downregulation and gonadotropin stimulation for an average of 11 days of stimulations. Most stimulations included only or mostly recombinant FSH, however in her second and third IVF cycle, Patient was given a mixed protocol which included recombinant FSH + urinary gonadotropins (Menopur). Each stimulation achieved a minimum of 2-5 lead follicles which reached sizes of greater than 18 mm. The average number of oocytes obtained between the four stimulations was 8. Fertilization was achieved with ICSI each time with fair success (degenerating eggs were occasionally encountered). In each of the four IVF cycles all embryos were allowed to grow to the blastocyst stage and between 2 to 3 blastocysts of fair to good quality were transferred.

Expert's Opinion

From the limited information I was provided, it is my understanding that Patient is a smoker. I have not received any information regarding medications Patient may be taking on a regular basis or any pertinent allergies. No information was received regarding Patient’s past gynecological history (aside from mild endometriosis), or past obstetrical history (aside from a first trimester miscarriage, which required a curettage procedure in 2004).
  1. Advanced maternal age.
  2. Mild male factor
  3. Mild endometriosis
  4. Failed IVF/ICSI x 5
  1. Obtain a hysterosalpingogram (HSG) if not previously done to rule-out a uterine abnormality or hydrosalpinx which could have affected implantation. If recently done, obtain films for review.

  2. Obtain menstrual day-3 FSH/estradiol lab work and baseline antral follicle count (AFC) via transvaginal ultrasound.

  3. In light of Gene’s smoking history, obtain Sperm Chromatin Structural Assay (SCSA) testing on Gene’s sperm to determine sperm DNA fragmentation index. Gene to begin using 100% - 200% of recommended daily allowances of antioxidants (Vit C, Vit E, Selenium, Zinc, L-carnitine…).

  4. In vitro fertilization without Buserelin for down-regulation. Stimulate with a mixed gonadotropin protocol in a 1:1 or close to 1:1 purified urinary:recombinant FSH ratio. Attempt to shorten length of stimulation (11 days as previously done is too long and may have led to the degeneration of some of the eggs upon fertilization) by changing stimulation to GnRH-antagonist protocol (or micro-flare). Consider addition of recombinant human Growth Hormone to stimulation to improve egg/embryo quality. Strongly consider avoiding a blastocyst transfer with next embryo transfer, and instead transfer embryos as day-3 cleavage stage embryos. Furthermore, consider initial embryo transfer of day-1 embryos the day following egg retrieval via laparoscopy into fallopian tubes [zygote intra-fallopian transfer (ZIFT)], then a standard day-3 embryo transfer with remaining embryos into uterus two days later. We have shown that in the face of repeated prior implantation failures, the combination ZIFT/IVF may yield superior results than standard IVF alone.