hypothyroidism is most common in women with TPOAb, although some women revert to euthyroidism. The incidence may be as high as 20%, and it may recur in subsequent pregnancies. The hyperthyroid phase may need to be distinguished from Graves’ disease which can present postpartum. Levels of T3 and TRAb can be useful. Symptomatic treatment with beta-blockers usually suf ces for the hyperthyroid phase, whereas the hypothyroid phase should be treated with thyroid hormone. As it can take over a year to determine whether a woman with postpartum thyroiditis requires lifelong thyroid hormone treatment, it is often wise to continue LT4 in women who are planning a subsequent pregnancy relatively soon. Postpartum thyroiditis can also occur after miscarriages, abortions, and ectopic pregnancies.

Summary

\1.\ Trimester and population-speci c normal ranges for TFTs musts be used during pregnancy.

\2.\ The majority of pregnant women with hypothyroidism require increased doses of LT4 throughout pregnancy.

\3.\ Pregnant women should take a prenatal vitamin with 150 μg iodine.

\4.\ The decision whether to screen for hypothyroidism prior to and during pregnancy should be individualized.

\5.\ Adverse pregnancy outcomes including loss and preterm birth are associated with a TSH >2.5 mIU/L and TPOAb positivity.

\6.\ LT4 should be titrated to a TSH <2.5 mIU/L for women with subclinical hypothyroidism undergoing ICSI and IVF.

\7.\ Maternal Graves’ disease should be treated with the lowest effective dose of PTU during the rst trimester, and the lowest effective dose of MMI thereafter, if needed.

\8.\ Transient gestational thyrotoxicosis, which is more common than Graves’ should not be treated with ATD.

References

1.\ Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during pregnancy and the postpartum. Thyroid. 2017;27(3):315–89.

2.\ Glinoer D, de Nayer P, Bourdoux P, Lemone M, Robyn C, van Steirteghem A, et al. Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab. 1990;71(2):276–87.

3.\ Casey BM, Thom ER, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, et al. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med. 2017;376(9):815–25.

Chapter 13

Infertility Evaluation

Owen Davis

Case

A couple presented with an 8-month history of primary infertility and no prior fertility evaluation. The female partner was 38 years old and nulligravid, and her male partner was also 38 and denied fathering any prior pregnancies. They had been engaging in unprotected intercourse of an average of two to three times per week and were trying to have intercourse every other day at mid-cycle. Previously they had used condoms for contraception.

The female partner indicated that her menarche had occurred at age 14 and that her cycles were regular, occurring every 24–25 days. She denied a history of sexually transmitted infections (STIs). She did have a history of one abnormal PAP test with positive HPV when she was in her 20s but with a normal colposcopy at that time and normal PAP tests ever since. She regularly experienced some premenstrual bloating and mild dysmenorrhea, which did not require analgesics. Her medical history was unremarkable except for mild irritable bowel syndrome managed through diet and lifestyle modi cations. Her surgical history was positive for prior wisdom tooth extraction. Her only current medication/supplements consisted of prenatal vitamins, and she denied any allergies. She denied smoking cigarettes or using recreational drugs and consumed an average of 1–2 alcoholic beverages per week. Her family history was noncontributory.

Her partner had a negative medical history; his surgical history was positive for treatment of a wrist fracture. His current medications/supplements included a daily multivitamin and occasional tadala l for situational erectile dysfunction with satisfactory results and no ejaculatory dysfunction. He denied any allergies. He

O. Davis (*)

Reproductive Medicine and Ob/Gyn, The Ronald Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA e-mail: okdavis@med.cornell.edu

P. H. Chung, Z. Rosenwaks (eds.), Problem-Focused Reproductive Endocrinology and Infertility, Contemporary Endocrinology, https://doi.org/10.1007/978-3-031-19443-6_13

pregnancy, pelvic infammatory disease [PID]), irregular cycles, amenorrhea, or a known male factor.

A thorough medical history should be elicited. The duration of infertility should be ascertained; primary infertility is diagnosed in the absence of prior pregnancies. In cases of secondary infertility, the outcomes of previous pregnancies should be noted. Where applicable, any prior fertility evaluation and treatments should be reviewed. A detailed menstrual history encompasses cycle length and regularity and the presence or absence of molimina and dysmenorrhea. The timing and frequency of intercourse should be discussed. A general medical and surgical history should be obtained to establish whether there are any other coexisting chronic or acute conditions and should include speci c inquiry regarding a possible history of STIs and/or PID, prior abdominal or pelvic surgeries, or evidence of endocrinopathies (hirsutism, galactorrhea, history of thyroid disease). Any current medications and supplements should be documented, including whether she is taking prenatal vitamins or supplemental folic acid. The family and social histories focus on genetic diseases, congenital malformations, and substance use/abuse (tobacco, alcohol, recreational drugs). A history should similarly be obtained from the male partner, including whether he had fathered prior pregnancies and additionally with a focus on possible sexual dysfunction and relevant medical conditions and surgeries (including urologic procedures, inguinal hernia repair) in addition to his family and social history.

The physical examination of the female partner includes vital signs and determination of her body mass index (BMI). The presence of hirsutism, acne, thyroid enlargement, and/or galactorrhea should be noted. A pelvic examination should be performed to assess for tenderness, uterine enlargement, or adnexal masses. Transvaginal sonography may be additionally performed to assess for possible ovarian cysts, antral follicle count, and uterine abnormalities (myomas, suspected adenomyosis).

The subsequent diagnostic evaluation should generally include assessment of ovarian function (ovulatory status and reserve), female anatomic factors (uterine and tubal), and the male factor. If indicated by the history or physical examination, further evaluation for peritoneal factors may be considered.

Normal fertility requires intact ovulatory function. Ovulatory dysfunction is diagnosed in approximately 15% of couples experiencing infertility and should be sought as part of the core fertility evaluation. If a patient has a history of regular menstrual cycles, ranging between 21 and 35 days, and experiences molimina (e.g., perimenstrual breast tenderness, bloating) and some degree of menstrual cramping, it is highly likely that she is ovulating, and it is a matter of some debate whether further documentation is necessary [1]. In addition, some patients will report detection of an LH-surge when utilizing home-based ovulation predictor tests. Nonetheless, it is reasonable to document presumptive ovulation with a peripheral serum progesterone determination performed in the expected luteal phase. A progesterone value exceeding 3 ng/mL is considered con rmatory [2]. A progesterone concentration in a higher range is not requisite, as ovarian progesterone secretion is pulsatile with signi cant variability throughout the day. Daily recording of the woman’s basal body temperature (to

and anatomy. Unilateral or bilateral proximal or distal tubal occlusion can be identi ed and speci cally the presence of hydrosalpinx in cases of distal obstruction. False positives are not uncommon, particularly in cases of suspected proximal tubal occlusion, as may occur with transient tubal spasm. Performance of an HSG may, in and of itself, have some therapeutic bene t in the setting of tubal patency, with enhanced pregnancy rates seen in the months following the procedure. The SIS entails the intracavitary instillation of sterile saline with concurrent ultrasound imaging. The SIS is a very sensitive modality for the detection of endometrial polyps, submucous myomas, and other uterine pathology; in contrast with the HSG, the echotexture of any identi ed intrauterine pathology can more speci cally suggest a polyp versus submucous myoma. Tubal patency can be inferred by the accumulation of saline in the cul-de-sac during an SIS, but one cannot as clearly distinguish unilateral versus bilateral tubal patency, and the tubal anatomy is less well de ned than with an HSG. If anatomic abnormalities are identi ed, various therapeutic options may be suggested, ranging from operative hysteroscopy for intrauterine pathology to laparoscopy for suspected endometriosis and/or pelvic adhesions and IVF for occlusive tubal disease. While routinely performed in the past, laparoscopy is no longer recommended as a standard diagnostic component of the female infertility evaluation, with potential exceptions being cases with identi ed pelvic pathology or signi cant symptomatology.

The fundamental initial laboratory evaluation of the male is the standardized semen analysis. The male partner is asked to produce an ejaculated semen sample after a speci ed abstinence interval, generally of 2–3 days. A complete analysis quanti es the volume of the ejaculate and determines the sperm concentration, percentage motility, and proportion of sperm exhibiting normal morphology. Per current World Health Organization criteria, normal semen parameters include: an ejaculate volume of at least 1.5 mL, sperm concentration of at least 15 million/mL, a sperm motility of 40% or greater, progressive motility of 32% or greater, and a morphology of 4% or greater normal forms [4]. Abnormal initial semen analysis bears repeating; when a male factor is identi ed, the male partner should be referred to a urologist or andrologist with a clinical focus on male infertility. Treatment options for the male can range from lifestyle modi cation to hormonal treatment, surgery for large varicoceles or anatomic obstruction, intrauterine insemination (IUI), IVF with intracytoplasmic injection (ICSI), or surgical sperm retrieval for use with IVF in cases of obstructive or non-obstructive azoospermia (absence of sperm in the ejaculate), depending on the underlying etiology and severity of sperm impairment.

In conclusion, in the case outlined at the outset of this chapter, a complete basic infertility evaluation revealed distal tubal occlusion (with hydrosalpinges) as the sole identi able etiology for this couple’s infertility and led to an effective therapeutic strategy, speci cally IVF, to successfully bypass the underlying pathology.