Treating Infertility
/Today we are thrilled to have Dr. Emily Seidler of the Division of Reproductive Endocrinology and Infertility at Beth Israel Deaconess and Boston IVF, come help us revisit Infertility with a discussion on treatment. We start out with definitions of fecundity versus fecundability, meaning:
Fecundity: Fertility; the ability to conceive and produce offspring, vs.
Fecundability = probability of getting pregnant in a single menstrual cycle.
For the first six months of attempted conception, 80% of couples will succeed. After one year, this jumps to about 85%, leaving a 15% rate of infertility overall based on the definitions we reviewed in our prior infertility episode.
Patients/couples should be initially counseled on lifestyle modification to improve fertility:
Stop smoking.
Reducing excessive alcohol/caffeine consumption.
Weight loss to target normal BMI.
Appropriately timing intercourse just before/around time of ovulation.
Use of OPKs starting around CD10
Once health and lifestyle is (reasonably) optimized, treatment may still be needed and varies depending on cause of subfertility/infertility.
We then started to talk about the specific causes of infertility. The first and most broad is ovulatory dysfunction. Ovulatory dysfunction is broken into major categories by the World Health Organization (WHO):
WHO class 1: hypogonadotropic hypogonadal anovulation (5-10%)
Common causes of this include anorexia, over-exercising, or Kallman’s and Sheehan’s syndromes.
These women need extensive nutritional support and hormonal support for bone and heart health.
To conceive, this group of patients will need injectable gonadotropins.
WHO class 2 = Normogonadatropic normoestrogenic (70-85%)
The most common example in this group is PCOS.
Treatment should focus on optimizing health (weight loss, improve/control insulin resistance, etc.) then ovulation induction with timed intercourse.
Letrozole is first line ovulation induction agent with PCOS.
NEJM 2014 comparing Clomiphene and Letrozole for PCOS.
Showed LTZ was associated with higher ovulation rates and higher live brith rates.
Clomiphene can also be used if can’t use letrozole or patient doesn’t respond to letrozole.
Clomiphene & Letrozole have different mechanisms of action but similar end result:
Clomid works at the level the brain as a SERM to inhibit negative feedback of estrogen on GnRH and FSH production/release.
Letrozole works at the level of the ovary and is an aromatase inhibitor, thus reducing the amount of estrogen available and pushing more production of FSH.
Both trick the brain into thinking estrogen is low, so FSH goes up.
WHO class 3 = hypergonadotropic hypoestrogenic anovulation (10-25%)
Classically described as primary ovarian insufficiency (POI)
Some can go through treatment with their own eggs, but often FSH is very elevated and AMH/AFC are very low- these patients generally need IVF donor eggs to conceive.
Next, we moved beyond ovulation to other causes of infertility.
Tubal factor:
I.e., both tubes are blocked.
Treatment is IVF, as this is only way to bypass the tubes in this case.
If hydrosalpinx, consider removing prior to treatment (these reduce pregnancy rate by 50% after embryo transfer when left in situ).
Male factor:
If sperm is present but in low counts (generally under ~4 mil total motile sperm), IVF with ICSI is helpful
ICSI = intracytoplasmic sperm injection.
One sperm injected into each egg under the microscope
If azospermic but male factor is an obstructive cause (i.e., cystic fibrosis patients with congenital absence of vas deferens), can surgically obtain sperm with TESE (testicular sperm extraction).
If azospermic and non-obstructive (i.e., patient isn’t making sperm), need donor sperm for conception.
Uterine factor:
This is generally not an independent cause of infertility or reason, in isolation, for surgical intervention.
However, when uterine factors that affect the cavity are found in an infertility evaluation, these are typically corrected prior to treatment.
Submucosal fibroids and endometrial polyps can be removed hysteroscopically .
Uterine septum or intracavitary adhesions can be resected hysteroscopically with cold scissors or with energy.
Unexplained infertility:
Testing all normal but unable to conceive after 6-12 mos; includes age-related subfertility.
Treatment is empiric (“cover the bases” approach).
Can start with medicated IUI with Clomiphene or Letrozole
If unable to conceive after 3-4 cycles, move on to IVF.
IVF can involve a fresh embryo transfer on day 3 or day 5, or frozen embryo transfers (always day 5).
Prenatal genetic testing for aneuploidy (PGT-A) is an adjunct to treatment (formerly called PGS).
This involves a trophectoderm biopsy at the blastocyst stage
Trophectoderm becomes the placenta; inner cell mass becomes the fetus.
Embryos generally are then frozen and biopsy samples are tested to determine chromosomal status
Used as a selection tool to transfer a single euploid embryo
Theoretically increases pregnancy rate to 60-70% and decreases miscarriage rate to 10%
However, recent studies (i.e., STAR trial) haven’t shown huge benefit to PGT-A over standard morphologic criteria for embryo evaluation.
Same sex couples/single patients:
Same sex female couples have options various therapies vs. traditional IVF
TDI = therapeutic donor insemination.
simply timing insemination with one partner’s menstrual cycle and using donor sperm.
Can also utilize ovulation induction techniques (i.e., letrozole/clomiphene).
Partner-assisted Reproduction (PAR), aka reciprocal IVF = using one partner’s eggs for conception, but the other partner carries the pregnancy.
Ovarian stimulation and egg retrieval on one partner.
Create embryos with donor sperm.
Transfer the embryo(s) into the other partner’s uterus.
Traditional IVF particularly if one partner is unable to conceive using TDI.
Same sex male couples require donor egg + gestational carrier.
Gestational carrier: just carrying the pregnancy.
Donor egg from a different woman; embryos created with one of the male partner’s sperm,
Traditional surrogacy typically refers to using the carrying woman’s egg, as well as her uterus. This has become very complicated legally and ethically and thus is not used with frequency.