Struggling With Infertility? Causes and Treatment Options

Infertility is the failure to conceive after one year of unprotected sexual intercourse. It affects approximately 10-15% of couples trying to conceive. While age decreases the fertility rate in women, there are many other reasons for infertility. And in some cases, fertility is simply unexplainable.

Infertility causes

The following factors can affect female fertility:

  • Cervical abnormalities: A narrowing or abnormality of the passageway through the cervix, which impedes sperm travel.
  • Uterine deformity: Congenital or acquired defects such as a septum or two cavities may cause early pregnancy loss or premature delivery.
  • Ovarian issues: Failure to ovulate is the most common infertility problem.
  • Tubal defects: Abnormalities or damage to the fallopian tube that may be congenital or acquired as in infection or pelvic inflammatory disease.
  • Peritoneal complications: Scarring from an infection, adnexal masses, or endometriosis.

Issues that can affect a male's fertility include:

  • Pretesticular causes: The result of congenital or acquired diseases of the hypothalamus, pituitary, or other organs that alter the hypothalamic-pituitary axis.
  • Testicular problems: These can be genetic or non-genetic.
  • Post-testicular complications: Congenital or acquired factors that disrupt the normal transport of sperm through the ductal system.

Factors that affect the fertility of both sexes include:

  • Environmental/occupational factors
  • Toxic effects from tobacco, marijuana, or other drugs
  • Excessive exercise
  • An inadequate diet is associated with extreme weight loss or gain
  • Advanced age

Treating infertility

Assisted reproductive technologies (ART) used to treat infertility include the following:

  • In vitro fertilization (IVF)
  • Gamete intrafallopian transfer (GIFT)
  • Zygote intrafallopian transfer (ZIFT)
  • Intracytoplasmic sperm injection (ICSI)
  • Intrauterine insemination (IUI)
  • Sperm, oocyte, or embryo cryopreservation

In 2006, 126,726 assisted reproductive technologies procedures were performed in the United States, broken down as:

  • In vitro fertilization: >99%
  • Gamete intrafallopian transfer: < 1.0%
  • Zygote intrafallopian transfer: < 1.0%
  • Cryopreserved embryos: 14%
  • Donor oocyte: 11%

The primary diagnosis leading to treating infertility with assisted reproductive technologies were as follows:

  • Tubal factor: 9.0%
  • Male factor: 17.0%
  • Endometriosis: 5.0%
  • Uterine: 1.0%
  • Ovulatory dysfunction: 6.0%
  • Diminished ovarian reserve: 13.0%
  • Unknown factor: 11.0%
  • Other factors: 9.0%
  • Multiple factors, female-only: 12.0%
  • Multiple factors, male and female: 17.0%

Drug treatments

Clomiphene citrate: Also called Clomid or Serophene, it is an oral pill that helps the ovulatory process. It can cause hot flashes, blurry vision, bloating, headaches, nausea, cervical mucus changes to the sperm’s detriment, and multiple births.

Metformin: A drug used for type II diabetes, it is used in polycystic ovarian syndrome to counter insulin resistance and help women ovulate. Women with polycystic ovarian syndrome have erratic cycles and can't ovulate regularly.

Human chorionic gonadotropin: With examples including Pregnyl, Ovidrel, or Novarel, it is a hormone that stimulates the release of an egg during ovulation. HCG is used to induce ovulation and causes the ovaries to make and release progesterone.

Femara or letrozole: This treatment lowers estrogen levels and is a common off-label drug used for infertility. This drug includes side effects such as:

  • Hot flashes, warmth or redness in your face or chest
  • Headache, dizziness, and weakness
  • Bone, muscle, or joint pain
  • Swelling or weight gain
  • Increased sweating

Gonadotropin-releasing hormones: These hormones are used in women who are not ovulating due to a lack of GnRH from the hypothalamus; GnRH stimulates the pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), both necessary to recruit an egg and cause its release during ovulation.

FSH and LH: Also known as menotropins or human menopausal gonadotropins (HMG), they stimulate the ovaries to produce and release eggs.

Menopur: This drug is a mixture of FSH and LH, which are important in developing follicles (eggs) produced by the ovaries in preparation for in-vitro fertilization.

Urofollitropin, intramuscular, or subcutaneous injection: Examples include Bravelle, Metrodin, and Fertinex, which are purified forms of FSH. This hormone is important in developing follicles (eggs) produced by the ovaries in women. It is used with other medications when there is an FSH deficiency.

FSH: This is for women whose ovaries work but whose eggs can’t mature regularly. Before receiving FSH, the first step is usually being treated with a drug called human chorionic gonadotropin (hCG).

Leuprolide-GNRH antagonists: This drug shuts down the hypothalamus from releasing GNRH and lowers FSH and LH release. It's often used in endometriosis as well as infertility.

GnRH antagonists: They keep the body from producing FSH and LH. These two hormones cause the ovaries to release eggs. By suppressing them, GnRH antagonists prevent spontaneous or early ovulation. These drugs allow the eggs to mature correctly to be used for IVF. GnRH antagonists are typically used with hCG. Two GnRH antagonists are Ganirelix acetate-subcutaneous injections and cetrotide.

Side effects of GnRH antagonists include:

  • Stuffy nose, sneezing, sore throat, cough with or without mucus
  • Fever, tiredness
  • Stomach pain
  • Nausea, vomiting
  • Constipation
  • Wheezing, chest tightness, difficulty breathing
  • Hot flashes, sweating
  • Dizziness, mood changes
  • Headache, pain
  • Vaginal swelling, itching, or discharge

The risk of taking injectable fertility drugs like HCG is ovarian hyperstimulation syndrome, which can be a life-threatening condition. It can cause severe pelvic pain due to large cysts forming on the ovaries, swelling of the hands or legs, stomach pain and swelling, shortness of breath, weight gain, diarrhea, nausea, vomiting, low blood pressure, and urinating less than normal.

In Vitro Fertilization

IVF consists of retrieving a preovulatory oocyte, an egg, from the ovary and fertilizing it with sperm in the laboratory, with subsequent embryo transfer within the uterus.

In the past, the absence of the fallopian tubes and severe pelvic adhesions were the absolute indications for IVF, but now patients with a history of endometriosis unsuccessfully treated medically or surgically can undergo IVF. Patients with a malformation of the uterus related to Diethylstilbestrol exposure, intrauterine adhesions, and septum are candidates. Men with severely low sperm counts or a history of obstruction in the tubes that transport sperm are also candidates for IVF. Couples who have failed more conservative therapies or with an unknown etiology of infertility are candidates for IVF.

IVF Procedure

IVF involves retrieving preovulatory eggs from the ovary and fertilizing them with sperm in the laboratory, with subsequent embryo transfer within the endometrial cavity.

The following steps are required during an IVF cycle:

  1. Ovarian stimulation makes an egg-filled cyst or follicle.
  2. Follicular aspiration, or egg retrieval, occurs. This process describes egg retrieval from the follicle.
  3. Oocyte classification occurs under a microscope.
  4. The sperm is prepared.
  5. Oocyte insemination occurs using sperm.
  6. An embryo culture has an incubation period either until it reaches a certain size or for a specific length of time.
  7. An embryo is transferred into the uterus.

Embryo and egg freezing

The American Society of Clinical Oncology’s guidelines on fertility preservation for adults and children with cancer include recommending that fertility preservation through the freezing of eggs or embryos should be discussed with all patients of reproductive age as early as possible in the treatment process. Oocyte cryopreservation is now considered standard practice. A patient interested in the process should see a reproductive endocrinologist.

Embryo cryopreservation became an important part of assisted reproductive technologies to prevent multiple pregnancies, prevent maternal and fetal complications, and decrease the cost of treatments as patients have the opportunity to achieve a pregnancy from one IVF cycle.

The embryos are stored in liquid nitrogen for an agreed-upon period, usually 3-5 years.

Frozen embryo transfer

Transferring frozen embryos can be performed during a natural menstrual cycle or an artificially stimulated cycle with the drugs described above. The embryos are thawed and then incubated 24 hours before embryo transfer.

Doctors perform pelvic ultrasonography to determine endometrial thickness. The live birth rate from frozen pre-embryos is 28.9%, which is less than the 35.7% rate achieved with a fresh embryo transfer.

The pregnancy rate for fresh cycles by patient age was approximate:

  • 44.7% among women younger than 35 years
  • 37.2% for the group aged 35-37 years
  • 27.6% of women aged 38-40
  • 17.7% of those older than 40 years
  • 9.2% for those aged 43-44 years

Women and men without functioning gonads can use donor eggs and sperm, but the fresh, not frozen protocol is used for eggs. Sperm may be fresh or frozen. When a couple can't use all of their frozen embryos, they may sometimes be donated and used.