Author: Eleni Pap.

Female infertility: What are the causes and how they are treated

Infertility is when a couple cannot get pregnant despite having frequent, unprotected sex for at least a year, and may result from an issue with the woman, with the man, or with both of them. The causes of female infertility include:

1. Age, which is related to a progressive decline in the quantity and quality of oocytes and a parallel increase in the frequency of chromosomal abnormalities.
2. Menstrual irregularities, such as irregular or absent menstrual periods due to anovulation, which are found in women with polycystic ovary syndrome, hyperprolactinemia, severe weight loss or excessive stress.
3. Fallopian tube issues, such as blockage, salpingectomy, wall damage or extended adhesions that alter tubal function and are often caused by inflammation of the fallopian tube or surgery.
4. Endometriosis which can affect the ovaries or/and the fallopian tubes.
5. Ovarian insufficiency, i.e. when ovaries show a reduced or absent ovarian reserve and ovarian function.
6. Uterine abnormalities, including congenital abnormalities, polyps, fibromas, adhesions or an absent uterus.

The treatment of female infertility should take into consideration all the relevant parameters in a couple, such as female age, sperm features, duration of infertility etc.

For menstrual irregularities due to anovulation, ovulation induction with fertility drugs is recommended, in order to conceive after regular sexual intercourse or intrauterine insemination.

Tubal damage, a damaged uterus, as well as endometriosis may require surgery. Laparoscopy or/and hysteroscopy are used to remove polyps and fibromas, divide and remove adhesions, perform resection (e.g. of a uterine septum) and treat endometriosis, whereas in fallopian tube blockage a salpingoplasty may be attempted.

Tubal issues that have never been dealt with or chosen to be dealt with surgically, or infertility that persists despite surgical treatment can be bypassed with IVF. Medically assisted reproduction is also proposed for women of advanced maternal age. IVF is a therapeutic option when all other methods (ovulation induction with sexual intercourse or intrauterine insemination) have not lead to the desired effects.

In patients with premature ovarian failure or early menopause, oocyte donation is the proposed solution, while, in patients that cannot get pregnant due to medical problems that prevent them from conceiving or due to an absent uterus, gestational surrogacy is a feasible method.

Fertility in women above 40

Infertility is defined  by the failure to achieve a clinical pregnancy after one year or more of regular unprotected sexual intercourse. Since 2015 has been described as a disease by the World Health Organization (WHO).

The causes are female (30%), male (30%) , mixed (male and female about 20%) and unexplained when no cause has been found in approximately 20% of cases.

Age is well established as the primary predictor of infertility treatments in women.

Once a woman reaches 40 her chances to achieve pregnancy naturally decline and is only about 5 % per each cycle.

For women ages 40 to 44, almost 30 % are infertile compared to only 15 % of women ages 30 to 34 and 7 % of women ages 20 to 25.

When women are born there ovaries contain a specific number of oocytes that are available in their reproductive age.

The mane reason of infertility regarding the age is the reduction of the number of oocytes available in the ovaries. As the ovarian reserve declines, the quality is also reduced by means of genetic abnormalities which leading to abnormal embryos enable to implant and follow a healthy pregnancy.

In addition, not only it is harder to get pregnant in this group of age but also the risk of miscarriage and give birth to a baby with chromosomal abnormalities is higher. At age 20 – 25, a woman’s risk of miscarriage is 10 %, at 30 – 35 the risk is 12 %, at 40 – 44 the risk 35%, and at over age 45 the risk of miscarriage is almost 55% according to ASRM (American Society of Reproduction Medicine).

The number of women older than 40 years having difficulty to conceive spontaneously and being treated for infertility has increased more than 10-fold in the last 15 years.

Before treatment a detailed investigation should be performed by a specialist. A personal medical history and a family history is imported to detect any personal or hereditary diseases which could be related to infertility. A vaginal ultrasound scan is also important to exclude anatomical pathologies as fibroids, polyps, ovarian cysts e.t.c. In addition a hormonal profile for evaluation of FSH, LH, Estradiol and thyroid function should be performed. Anti Mullerian Hormone (AMH) in combination with the ultrasound scan can give us information about the ovarian reserve.

There are different types of treatment available and should be individualized according to the history of each woman and the cause of infertility.

Intrauterine insemination is relatively painless and non invasive procedure which can be performed in a natural cycle or with ovarian stimulation.

IVF is the most effective and commonly performed treatment in this group of age.  The are different protocols that can be used. With the natural cycle a single oocyte obtained by aspiration of the follicle either with local anesthetic or with sedetion , fertilized in the lab and transferred in to the uterine cavity usually  3 to 5 days afterwards. Embryos that reach in the 5th day (blastocysts) have more chances to implant.

The ovarian stimulation is more effective as we obtain a higher number of oocytes/embryos. The most common protocols are the long one and the short with antagonist with a mean of 9-10 days of stimulation. The embryo transfer in blastocyst stage increasing again the rate of success.

Pre implantation diagnoses for aneuploidy screening (PGS) has been used to detect chromosomally euploid embryos. A biopsy of the embryos performed usually at the blastocysts stage and only the euploid (chromosomally healthy) embryos used. This method increasing the rate of success and decreasing the miscarriage rate in  women with advanced age.

Oocyte donation is a very effective method for women with low quality oocytes, ovarian disfunction or repeated implantation failure.

As fertility decline with age, women in 30-35 years old who do not think to conceive either for medical or social reasons, preservation of oocytes or ovarian tissue is an effective method so that can use them in the future.

Endometriosis and IVF

Endometriosis is a common but still enigmatic gynecological disorder, affecting 3-43% of reproductive age women and is diagnosed in 6-10% of women undergoing assisted reproduction techniques (IVF/ICSI).

The unclear benefit of laparoscopic management of minimal/mild endometriosis associated infertility becomes needless in case of patients with stage I-II undergoing IVF/ICSI, since its application is not associated with increased pregnancy and live birth rates after IVF/ICSI.

As far as the impact of endometriotic cyst (Stage III-IV) on the outcome of in-vitro fertilization is concerned, the most recent meta-analysis (Chun Yang et al., RBM Online, 2015) clearly showed that its presence is associated with lower oocytes, lower MII oocytes and lower number of embryos, although the clinical pregnancy and live birth rates were comparable. On the other hand one should take into account the possible impact of surgery on ovarian reserve and, also, the rupture of the cyst during oocyte retrieval, which may lead to peritonitis.

Laparoscopic management of deep infiltrating endometriosis (DIE) showed inconsistent results with regard to achievement of pregnancy after IVF/ICSI. Obviously, the effective management of chronic pelvic pain in case of DIE represents the main indication for surgical approach.

Management decisions should be individualized, taking into account and other confounding infertility factors, age, ovarian reserve and preference of the patient, while it is more than obvious that the design of prospective, well-designed studies is of utmost importance.