Use of High Cost Monitoring During Letrozole Ovulation Induction

• Cost per conception [ Time Frame: 4 cycles or upon conception ] [ Designated as safety issue: No ]
• Time to conception [ Time Frame: 4 cycles or upon conception ] [ Designated as safety issue: No ]

The purpose of this study is to investigate monitoring methods during ovulation induction cycles with letrozole and their effect on pregnancy rates. Monitoring ovulation induction cycles with letrozole can be done with a variety of methods, the two most commonly utilized are home-based urinary LH kits (or ovulation predictor kits) and office-based midcycle follicular ultrasound. Letrozole coupled with follicular monitoring by ultrasound may add extra cost per cycle with no improvement in fecundability (pregnancy rates per cycle).

The study will be a randomized controlled trial of adult women with primary and secondary infertility seen at the University of Michigan Health System undergoing ovulation induction (OI) with letrozole as part of their standard clinical care. Patients who are undergoing OI with letrozole as per standard clinical care will be randomized to urinary luteinizing hormone (LH) ovulation predictor kit use versus mid-cycle ultrasound with administration of hCG when appropriate for timing of intercourse or intrauterine insemination. Patients who have been prescribed letrozole as per routine clinical care will be approached to determine willingness to participate in this study. Study period involves up to four ovulation induction cycles or until pregnancy occurs.

• Other: Midcycle ultrasound + hCG injection
  Mid-cycle ultrasound with administration of hCG (single dose of standardized pre-filled injection, 250 mcg, at time of ultrasound) when appropriate.
  Other Name: Ovidrel
• Other: Urinary LH kits
  Subjects randomized to monitoring with LH kits at home will keep a monthly calendar documenting when LH testing begins, day LH surge occurs and day(s) of intercourse/insemination.
  Other Name: ClearBlue Easy

• Active Comparator: Group A
  Patients randomized to this arm will monitor ovulation with home-based urinary LH kits (Ovulation Predictor Kits, OPK's).
  Intervention: Other: Urinary LH kits
• Active Comparator: Group B
  Patients randomized to this arm will undergo ovulation monitoring with midcycle ultrasound and receive hCG injection if evidence of a mature size follicle.
  Intervention: Other: Midcycle ultrasound + hCG injection

• Pritts EA. Letrozole for ovulation induction and controlled ovarian hyperstimulation. Curr Opin Obstet Gynecol. 2010 Aug;22(4):289-94. Review.
• Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril. 2001 Feb;75(2):305-9.
• Mitwally MF, Abdel-Razeq S, Casper RF. Human chorionic gonadotropin administration is associated with high pregnancy rates during ovarian stimulation and timed intercourse or intrauterine insemination. Reprod Biol Endocrinol. 2004 Jul 7;2:55.
• Deaton JL, Clark RR, Pittaway DE, Herbst P, Bauguess P. Clomiphene citrate ovulation induction in combination with a timed intrauterine insemination: the value of urinary luteinizing hormone versus human chorionic gonadotropin timing. Fertil Steril. 1997 Jul;68(1):43-7.
• Zreik TG, García-Velasco JA, Habboosh MS, Olive DL, Arici A. Prospective, randomized, crossover study to evaluate the benefit of human chorionic gonadotropin-timed versus urinary luteinizing hormone-timed intrauterine inseminations in clomiphene citrate-stimulated treatment cycles. Fertil Steril. 1999 Jun;71(6):1070-4.
• Lewis V, Queenan J Jr, Hoeger K, Stevens J, Guzick DS. Clomiphene citrate monitoring for intrauterine insemination timing: a randomized trial. Fertil Steril. 2006 Feb;85(2):401-6.
• Smith YR, Randolph JF Jr, Christman GM, Ansbacher R, Howe DM, Hurd WW. Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction. Fertil Steril. 1998 Jul;70(1):165-8.

Inclusion Criteria:

• Women ages 21-39 undergoing letrozole ovulation induction (as part of routine clinical care) at a single academic-infertility center.
• Normal uterus and evidence of at least tubal patency on one side (as assessed by saline-infusion sonography or hysterosalpingogram per clinical care).

Exclusion Criteria:

• Current pregnancy
• Nursing mothers
• Prior hypersensitivity to hCG preparations
• Primary ovarian failure or menopausal levels of FSH (>12 mIU/mL)
• Patients with abnormal uterine bleeding of undetermined origin or ovarian cyst of undetermined origin, sex-hormone dependent tumors, documented bilateral tubal obstruction, uncorrected uterine anomalies,
• Previous letrozole or gonadotropin use and/or previous treatment with in vitro fertilization
• Other uncorrected medical condition that would be a contraindication to attempting elective ovulation induction (e.g., uncontrolled diabetes, intracranial lesion, thyroid or adrenal disease).