Subclinical Hypothyroidism Compared in IUI Cycles

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Normal but elevated thyroid levels compared in IUI cycles

Impact of preconceptional serum thyroid stimulating hormone values ranging between 2.5 and 4.5 mIU/L on live birth rates following ovulation induction and intrauterine insemination treatment for unexplained infertility

A retrospective study was carried out to determine any difference in outcomes for euthyroid (normal thyroid) women, with thyroid stimulating hormone (TSH) levels below 2.5 mIU/L and also between 2.5 to 4.5 mIU/L, with unexplained infertility undergoing ovulation induction (OI) and intrauterine insemination (IUI).

Couples with unexplained infertility who underwent ovulation induction and intrauterine insemination, at the Kanuni Sultan Suleyman Research and Training Hospital, between January 2013 to December 2018 were initially assessed for inclusion in the study.

Exclusion criteria included thyroid medication or disease, thyroid autoimmunity, BMI < 18 or > 35, antral follicle count < 8 or > 24, polycystic ovary syndrome, male factor infertility, endometriosis, tubal pathology, other endocrine or chronic systemic diseases, cancelled cycles or timed intercourse cycles.

Unexplained infertility was defined as normal ovarian reserve and sperm parameters, ovulatory cycles (mid-luteal progesterone), bilateral tubal patency and normal uterine anatomy (hysterosalpingography) who did not conceive following regular sexual intercourse for at least 12 months (or 6 months if woman ≥ 35 years).

Ovarian stimulation was initiated with 50-75 IU/day of subcutaneous recombinant follicle stimulating hormone (rFSH) dependent on patient characteristics (age, AFC, BMI). Transvaginal ultrasound was used to monitor ovarian response and guide dosage levels along with duration of stimulation. Once one or two follicles reached a mean diameter of 18µm, ovulation was induced with a hCG trigger hot followed by IUI 36 hours later. Semen samples were collected 2 hours prior to IUI, following 2-3 days of sexual abstinence, and concentrated using the swim-up technique. Following insemination, luteal support (vaginal progesterone gel) was administered twice a day until the 9th week of gestation.

In this study, clinical pregnancy was defined by ultrasound confirmation of foetal cardiac activity at the 7th week of gestation, while delivery of a viable baby after the 24th week of pregnancy was deemed a live birth.

A total 726 euthyroid women, 543 in Group 1 (TSH 0.27–2.5 mIU/L, 1110 cycles) and 183 in Group 2 (2.51–4.5mIU/L, 355 cycles) were included in the study. Comparison of patient characteristics among the two groups showed no statistically significant difference across all categories including age, BMI, duration of infertility, antral follicle count, total motile sperm count, type of infertility (primary/secondary), history of pelvic surgery, smoking habits and basal assessment.

Analysis of outcomes showed the clinical pregnancy rate per cycle was 8.6% and 7.9%, for Group 1 and Group 2 respectively, with no statistical significance (P=0.74). Similarly live birth rate per cycle was 8.1% and 7.1%, for Group 1 and Group 2 respectively, with again no statistical significance (P=0.38).

Further analysis of secondary outcomes; duration of ovulation induction, total gonadotrophin dose, number of follicles on trigger day and miscarriage rate per cycle, did not show any statistically significant differences between the 2 Groups featuring different TSH levels.

The authors noted that although no difference was found in IUI cycles, TSH levels have been shown to increase in response to supra-physiologic estradiol levels, induced by IVF/ICSI cycles, suggesting treatment may still be beneficial in women with TSH levels > 2.5 mIU/L in such ART cycles.


SUMMARY: IDEAL THYROID LEVELS FOR FERTILITY

According to this study, thyroid (TSH) levels below 4.5mIU/L had no statistically significant effect on fertility outcomes, in women diagnosed with unexplained infertility undergoing IUI, achieving live birth rates per cycle of 8.1% for TSH 0.27–2.5 mIU/L, and 7.1% for TSH 2.51–4.5mIU/L, P=0.38.


Limitations

  1. Retrospective study
  2. Anti-TPO status not evaluated
  3. TSH levels post ovulation induction was not measured


Similar studies

Pekcan M K, et al. (2019). Impact of subclinical hypothyroidism and thyroid autoimmunity on clinical pregnancy rate after intrauterine insemination in Euthyroid women. https://doi.org/10.5935/1518-0557.20190027

Repelaer van Driel-Delprat CC, et al. (2019). Live birth rate after intrauterine insemination is not different between women with lower quartile versus higher quartile normal range thyroid stimulating hormone levels. https://doi.org/10.1093/hropen/hoz002

Turgay B, et al. (2019). The association of thyroid stimulating hormone levels and intrauterine insemination outcomes of euthyroid unexplained subfertile couples. https://doi.org/10.1016/j.ejogrb.2019.06.022

Jokar T O, et al. (2018). Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility. https://doi.org/10.1210/jc.2017-02120

Tuncay G, et al. (2018). The impact of thyroid-stimulating hormone levels in euthyroid women on intrauterine insemination outcome. https://doi.org/10.1186/s12905-018-0541-0

Karmon A E, at al. (2015). Preconceptional thyroid-stimulating hormone levels and outcomes of intrauterine insemination among euthyroid infertile women. https://doi.org/10.1016/j.fertnstert.2014.09.035


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