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Anovulation Treatments

Anovulation (a lack of ovulating) can be caused by a wide range of issues and is affected by lifestyle, diet, medication and exercise. It’s by far the most common condition that affects women who go to fertility clinics, and about 70% of the time, it’s PCOS, but there are five other causes of the condition.

  1. Luteinised unruptured follicle syndrome (LUFS)
  2. Low hormone levels in a condition called “hypogonadotrophic hypogonadism”
  3. High hormone levels in a condition called “hyperprolactinaemia”
  4. Premature ovarian failure (POF)
  5. Genetic conditions can be the cause in exceptional cases

We have built a special package for PCOS, explaining the specific tests, treatments and self-help advice as part of our membership package. There are specific tests to discover the cause of anovulation, as Investigations for anovulation explain. In addition to this, the treatment options for the different conditions are in the articles on these conditions:

  • LUFS
  • POF
  • Hypogonadotrophic hypogonadism
  • Hyperprolactinaemia

10 Treatments for Anovulation

There are effective treatments for anovulation that range from self-help to drugs and surgery. For the majority, improving their health is the most effective thing they can do. There are also supplements and holistic treatments that adjust an imbalanced hormone profile and usually promote ovulation again. For some women, this isn’t enough, and they need extra help to ovulate.

1. Clomifene citrate (clomid)

Clomid is usually the first line of medical treatment, and it’s an anti-estrogen that blocks estrogen receptors in the hypothalamus. The effect is higher Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH) production from the anterior pituitary, which should stimulate at least one dominant follicle to ovulation.

  • The hypothalamic-pituitary axis must be functioning, as is the case with polycystic ovary syndrome (PCOS).
  • 70% of women with PCOS ovulate with Clomid, and 40-60% conceive within six months. About 10% have twins and 1% have triplets.
  • Ultrasound monitoring is advised as Clomid increases the risk of ovarian hyper-stimulation syndrome (OHSS). i

Possible side effects are hot flushes, mood swings, nausea, breast tenderness, insomnia, increased urination, heavy periods, spots, weight gain and OHSS. It’s linked to thinning of the womb lining, less fertile mucus, greater risk of ectopic pregnancy and miscarriage, as well as LUFS. The Committee on Safety of Medicines in the UK recommends taking Clomid for a maximum of six months.

2. Medicinal Herbs

Combinations of medicinal herbs have been used for centuries to promote fertility and trigger ovulation with great success and without significant side effects: ii A meta-analysis of 1850 women who had personalised herbal combinations for unexplained infertility found the herbs were:

  • 1½ times more effective than Clomid at increasing ovulation
  • Over three times more likely to result in pregnancy than standard drug treatments.
  • Achieving pregnancy rates of about 60% in four months, while standard fertility drug treatment or IVF achieved rates of 30% in 12 months. iii
  • Significantly lower miscarriage rates of 20% for those with Clomid.
  • Able to dramatically improve the quality of cervical mucus (crucial for natural pregnancy) compared to Clomid.

3. Metformin

Metformin is an insulin-sensitising agent used in Type II diabetes treatments. It’s often used in PCOS treatments (alongside Clomid) as insulin resistance is an integral part of PCOS development. It’s been an important addition to PCOS management, and two reviews show it reduces menstrual irregularity and improves ovulation rates. However, natural alternatives are as effective without the side effects, and they also improve general health.

Possible side effects are nausea, vomiting, diarrhoea, abdominal pain, a metallic taste, itching, and allergic reactions. These issues can lead to an intolerance to the drug and high dropout rates.

4. N-acetyl-cysteine (NAC)

NAC is a viable alternative to metformin as an insulin-regulating agent. NAC has a traditional use to thin cervical mucus and increases antioxidant levels. Studies have shown it also improves circulating insulin levels and increases insulin sensitivity in women with PCOS. It may improve Clomid treatment for women with PCOS and may be as effective as metformin in reducing insulin levels, restoring menstrual regularity and reducing testosterone. The women also have a significant reduction in total and LDL (bad) cholesterol without adverse side effects. iv

5. Inositols

Inositols are DCI-IPG mediators that control what happens to sugars once they arrive in cells. There’s overwhelming evidence they’re a crucial part of the development of insulin resistance. They can play an essential role in reversing insulin resistance and PCOS. Please see PCOS treatments for excellent information on this.

6. Weight loss

Weight loss is a central part of lifestyle changes for anovulation. It can radically alter the hormone balance of overweight women with PCOS. Losing 5-10% of total body weight reduces central body fat by up to 30%, improves insulin sensitivity and restores ovulation:

  • Overweight women with PCOS need to lose weight until their BMI is below 30 before starting drugs for ovarian stimulation ix
  • Losing weight is usually the best way to improve hormone balance and pregnancy outcomes for women with PCOS x
  • Being overweight (or obese) reduces the chances of getting pregnant or having a healthy pregnancy xi
  • The risks of complications are higher in obese women. Simply because it’s harder to control hormone levels or track follicles with ultrasound

Lifestyle has more information on how weight affects fertility.

7. Weight gain

Gaining weight is crucial for underweight women who don’t ovulate. An illness, anorexia nervosa, or over-exercise can cause weight loss and lower leptin levels. Fat cells release the hormone-like cytokine leptin, so low-weight, vegan or low-fat diets can reduce leptin levels. Leptin is essential to make the hormones needed to trigger new menstrual cycles. Having an adequate intake of healthy fats is essential, and gonadotropin injections to induce ovulation are an option but carry risks to the mother or the baby.

Mothers with low leptin levels have a higher risk of miscarriage, stillbirth, and the chance of a small baby arriving prematurely. Low leptin increases the risks for the long-term health of both the child and mother and highlights the importance of women optimising health before having a family.

8. Follicle-stimulating hormone (FSH)

FSH injections are a treatment option used when the ovaries are working well, but the hypothalamic-pituitary axis isn’t. FSH can also be used when women with PCOS don’t respond successfully to Clomid.

9. Surgical induction

Surgical “drilling” of the ovary requires a laparoscope and a laser to puncture several holes into an ovary to encourage ovulation. The success rates are comparable with FSH injections, but it has lower risks of multiple pregnancies or OHSS. This surgery isn’t without risk, including adhesions following surgery and the increased risk of premature ovarian failure if too much ovarian tissue is removed.

10. Gonadotrophin releasing hormone (GnRH) pump

For women with a purely hypothalamic cause of anovulation, a GnRH pump may be the answer. Examples include women who’ve recovered from weight-related amenorrhoea but aren’t ovulating. They can wear a small patch with a pump syringe that releases GnRH at timed intervals. GnRH pumps usually trigger ovulation, and conception rates are similar to the norm at around 20-30% per cycle and 80-90% in a year.


References
i Royal College of Obstetricans and Gynaecologists’ guidelines, No 3.
ii ‘Chinese herbal medicine for infertility with anovulation: a systematic review.Tan L et al. J Altern Complement Med. 2012 Dec;18(12):1087-100.
iii ‘Efficacy of Traditional Chinese Herbal Medicine in the management of female infertility: A systematic review.’ Karin Ried, Keren Stuart Complementary Therapies in Medicine (2011) 19, 319—331
iv ‘Clinical, endocrine and metabolic effects of metformin vs N-acteyl-cytseine in women with polycystic ovary syndrome’. Oner G, Muderris I. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2011;159:127-131.
vD-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review.’ Galazis N, et al. Gynecol Endocrinol. 2011 Apr;27(4):256-62. doi: 10.3109/09513590.2010.538099. Epub 2010 Dec 10.
viMyo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, rrandomisedtrial.Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, De Santis L. Fertil Steril. 2009 May;91(5):1750-4. doi: 10.1016/j.fertnstert.2008.01.088. Epub 2008 May 7.
vii ‘Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study.’ Lisi F, et al. Reprod Biol Endocrinol. 2012 Jul 23;10:52. doi: 10.1186/1477-7827-10-52.
viiiThe Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients.Minozzi M, Nordio M, Pajalich R. Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):537-40.
ixPCOS, obesity and reproductive function: RCOG Special Study Group on Obesity.’ Balen AH.  2007. London: RCOG Press
x  ‘Improving reproductive performance in overweight/obese women with effective weight management.Norman RJ, Noakes M, Wu R, Davies MJ, Moran L, Wang JX. Hum Reprod Update. 2004 May-Jun;10(3):267-80
xi ‘Should obese women with polycystic ovary syndrome receive treatment for infertility?’ Balen AH, Dresner M, Scott EM, Drife JO. BMJ. 2006 Feb 25;332(7539):434-5.
Photo: “https://unsplash.com/Kajetan Sumila

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