Next Fertility IVF Prof. Zech

Stimulation

Ovarian Stimulation

During the normal menstrual cycle the woman's ovaries tyically produce a single dominant follicle resulting in a single mature egg cell each month (follicle growth / ovary). In each cycle there is a cohort of about 10 follicles competing against one another for dominance. Only one of them is able to develop into the dominant follicle containing the mature egg. This is precisely where hormonal stimulation comes into play: The woman receives appropriate hormonal treatment (e.g. gonadotropins = pituitary hormones) in order to induce the growth and maturation of multiple egg-containing follicles which would otherwise not have reached maturity. In this context, it is reassuring to know that ovarian stimulation is not associated, as is often incorrectly assumed, with premature menopause in women.

Schematic diagram of follicle growth in the female ovary


1. Hormonal treatment
2. Stimulation protocol
3. Intake of medication
4. Ultrasound monitoring
5. Video tutorials


1. Hormonal treatment

Ovarian stimulation requires a suitable preparation. On the one hand, it is necessary to determine the serum levels of specific hormones. On the other hand, it is essential to perform an ultrasound scan to assess the "Antral Follicle Count - AFC" (= number of smaller follicles visible by ultrasonography). In addition, the womb is examined by ultrasound to determine the exact position of the ovaries and to identify the possible presence of myomas and/or polyps. Based on the hormone status, the "Antral Follicle Count" and the ultrasound examination of the uterus, it is possible to make a forecast of the woman's anticipated response to ovarian stimulation.

Schematic diagram of hormonal treatment: period of time, ovarian cycle, active hormones, build up of uterine lining │ © 2022 Next Fertility IVF Prof. Zech • Member of Next Clinics


Controlled ovarian stimulation to induce the growth of multiple follicles (containing the ova) inside the ovaries requires the administration of several drugs or hormones for a certain time. Different stimulation protocols are used depending on the type of treatment, such as, for instance intra-uterine insemination (i.e. the transfer of sperm, also called spermatozoa into the uterine cavity) or the retrieval of oocytes by follicular aspiration (involving the subsequent insemination of the obtained oocytes with sperm in a test tube). In order to stimulate the growth of multiple ovarian follicles, we typically use hormones that are found in the female body (gonadotropins). In the majority of cases, these hormones are administered by injection either into a muscle (i.e. intramuscular) or under the skin (i.e. subcutaneous) (→ see "3. Intake of medication").

2. Stimulation protocol

Before and during the treatment, the couple is often confronted with a multitude of impressions and information. This may be confusing and can at times even provoke fear of doing something wrong. This holds especially true for couples having embarked on ovarian stimulation. After receiving appropriate patient education and relevant instructions at the IVF center, they are expected to carry out the injections themselves at home. Extremely poor response to stimulation could mean having to discontinue the treatment. The presence of ova is required to allow the union of egg and sperm (provided by the male partner). Thus, such hormonal treatments require a high level of patient compliance, which however can be achieved thanks to a customized stimulation protocol. The protocol provides the couple with detailed instructions as to how and when they should administer the prescribed medicines. In addition, video tutorials covering the proper preparation and injection of medications can be very helpful (→ see "5. Video Tutorials").

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3. Intake of medications

Targeted hormonal tratment is aimed at stimulating a woman's ovaries. To this end, different medications are used wherein these hormones are contained. Depending on the individual drug, the route of injection may vary: into the muscle (intramuscular injection) and/or under the skin (subcutaneous injection).

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Intramuscular Injection (IM)

Intramuscular injection delivers a fluid medication deep into a skeletal muscle by means of a syringe and a cannula. The following medications should be administered by intramuscular injection: gonadotropins (e.g. Merional, Menogon, Menopur), human chorionic gonadotropin (e.g. Pregnyl (A, CH) = Predalon (D), Brevactid, Gonasi), progesterone (e.g. Agolutin, Gestone, Prontogest, Progesteron Streuli)

Injection needles:
To dissolve the medication, please use the blunt needles 18G / 1,2 x 40mm. For intramuscular injection, please use the green needles 21G / 0,8 x 40mm.

Performing the intramuscular injection:

  • Locating injection site
  • Preparing injection solutions (in the case of dry substances (powder) e.g. Merional, Fostimon, Menogon, Menopur, Pregnyl etc): The medicine is contained in the powder, the liquid serves as the solvent. Inject the liquid into the powder. The powder dissolves instantly and can be drawn up into the syringe. When preparing the solution, please make sure to use the same number of vials (ampoules) filled with liquid and vials containing powder, e.g. mix 3 x powder with 3 x liquid.
  • Disinfection of the puncture site
  • Required contact time of the disinfectant must be observed (about 30-60 seconds)
  • Replace the injection needle (use green needle for injection, assemble the needle tightly onto the syringe!)
  • Swiftly insert the needle at a 90-degree angle - The cannula (needle) should NOT be inserted completely. Inject slowly!

Subcutaneous injection (SC)

The term subcutaneous refers to the anatomic location of the injection site, i.e. injection into the layer of tissue just "under the skin". This subcutaneous tissue essentially consists of connective and fatty tissues located just beneath the skin. The following medications should be administered by subcutaneous injection: GNRH-Agonist and -Antagonist (e.g. Decapeptyl, Orgalutran, Cetrotide), gonadotropins (e.g. Puregon, Gonal F, Fostimon)

Injection needles:
To dissolve the medication, please use the blunt needles 18G / 1,2 x 40mm. For subcutaneous injection, please use the short needles 27G / 0,40 x 20mm. Puregon and Gonal-F come in a pen, including single-use disposable pen needles (e.g. 29G / 0,33 x 12mm or BD Micro-Fine Pen Needle)

Performing the subcutaneous injection:

  • Locating injection site: You can inject in your abdomen under the level of the belly button or into the front of the thigh. Pinch the skin at the desired puncture site to make sure that the injection is given into the subcutaneous tissue and not the muscle tissue. Insert the needle at a 45-90 degree angle to the skin surface.
  • Preparing the injection solution: for dry substances (powder) see section 1.2 Intramuscular Injection. Some injectable medications are available as ready-to-use injection solutions in a pre-filled drug delivery system. There are specific PENs for the self-administration of Puregon or Gonal-F: see instructions for use (package leaflet)
  • Disinfection of the puncture site
  • Required contact time of the disinfectant must be observed (about 30-60 seconds)
  • Replace the injection needle (use grey needle for injection, assemble the needle tightly onto the syringe!) / for Puregon and Gonal F Pens 29G / 0,33 x 12mm or BD Micro-Fine Pen Needle
  • Swiftly insert the needle at a 45-degree angle, gently press down on the plunger of the syringe to inject the medication at a slow but steady rate.

4. Ultrasound monitoring

We are using cutting-edge 3D ultrasound systems for monitoring follicular growth (follicle monitoring). This is a precise, automated system for measuring the size and volume of developing follicles, whilst at the same time enabling us to make more accurate predictions as to their degree of maturity than would be possible using conventional ultrasound techniques. Scientific evidence suggests that those oocytes retrieved during follicular aspiration following follicle monitoring by 3D ultrasound show a higher fertilization potential. The ultrasound examinations are performed at regular intervals throughout the entire stimulation phase. The aim is to determine the optimum time for the administration of the hCG trigger-shot and the subsequent egg retrieval procedure.

How to administer medicines correctly

Videos and explanatory notes on how to prepare and inject the medications used for ovarian stimulation:

5. Video Tutorials

Ovarian Stimulation | Preparation Merional® | Patient Guide

Ovarian Stimulation | Preparation Pregnyl® | Patient Guide