Reproductive Rounds

Top 10 unproven infertility tests and treatments


4. Prescribing clomiphene citrate without IUI

Ovulation dysfunction is found in 40% of female factors for fertility. Provided testing reveals a reasonably normal sperm analysis and hysterosalpingogram, ovulation induction medication with ultrasound monitoring along with an hCG trigger is appropriate. In women who ovulate with unexplained infertility and/or mild male factor, the use of clomiphene citrate or letrozole with timed intercourse is often prescribed, particularly in clinics when IUI preparation is not available. Unfortunately, without including IUI, the use of oral ovarian stimulation has been shown by good evidence to be no more effective than natural cycle attempts at conception.4

5. Thrombophilia testing

Recurrent miscarriage, defined by the spontaneous loss of two or more pregnancies (often during the first trimester but may include up to 20 weeks estimated gestational age), has remained an ill-defined problem that lacks a consensus on the most optimal evaluation and treatment. In 2006, an international consensus statement provided guidance on laboratory testing for antiphospholipid syndrome limited to lupus anticoagulant, anticardiolipin IgG and IgM, and IgG and IgM anti–beta2-glycoprotein I assays.5 ASRM does not recommend additional thrombophilia tests as they are unproven causative factors of recurrent miscarriage.

6. Screening hysteroscopy

A standard infertility evaluation includes ovulation testing, assessment of fallopian tube patency, and a sperm analysis. In a subfertile women with a normal ultrasound or hysterosalpingogram in the basic fertility work‐up, a Cochrane data review concluded there is no definitive evidence for improved outcome with a screening hysteroscopy prior to IUI or IVF.6,7 Two large trials included in the Cochrane review, confirmed similar live birth rates whether or not hysteroscopy was performed before IVF. There may value in screening patients with recurrent implantation failure.

7. PGT-A for all

As the efficacy of the first generation of embryo preimplantation genetic testing, i.e., FISH (fluorescence in situ hybridization) was disproven, so has the same result been determined for PGT-A, specifically in women younger than 35.8 In an elegant randomized prospective trial, Munne and colleagues showed no improvement in the ongoing pregnancy rate (OPR) of study patients of all ages who were enrolled with the intention to treat. However, a subanalysis of patients aged 35-40 who completed the protocol did show an improved OPR and lower miscarriage rate per embryo transfer. While there is no evidence to support improved outcomes with the universal application of PGT-A, there may be some benefit in women older than 35 as well as in certain individual patient circumstances.

8. ICSI for nonmale factor infertility; assisted hatching

In an effort to reduce the risk of fertilization failure, programs have broadened the use of ICSI to nonmale factor infertility. While it has been used in PGT to reduce the risk of DNA contamination, particularly in PGT-M (monogenic disorder) and PGT-SR (structural rearrangement) cases, ICSI has not been shown to improve outcomes when there is a normal sperm analysis.9 During IVF embryo development, assisted hatching involves the thinning and/or opening of the zona pellucida either by chemical, mechanical, or laser means around the embryo before transfer with the intention of facilitating implantation. The routine use of assisted hatching is not recommended based on the lack of increase in live birth rates and because it may increase multiple pregnancy and monozygotic twinning rates.10

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