Complications of Ovarian Stimulation: Multifollicular Development

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Complications of Ovarian Stimulation: Multifollicular Development



Evert J.P. van Santbrink




Introduction


Ovarian stimulation in patients with chronic anovulation, traditionally classified as WHO classes 1 and 2 (see Chapters 14 through 16), is aiming at restoration of physiology: monthly follicular maturation and ovulation of a single dominant oocyte.


Conventional treatment is considered to be administration of gonadotropin-releasing hormone agonist (GnRH-agonist) or gonadotropins in WHO 1 anovulation and anti-estrogen (clomiphene citrate) followed, in case of treatment failure, by exogenous follicle-stimulating hormone (FSH) in WHO 2 patients. More recently, aromatase inhibitors as a new ovulation induction compound have been introduced for treatment of WHO 2 anovulation.


Regardless of the means used, it is often hard to control ovarian stimulation, resulting in multiple follicle development and ovulation. This may enable chances for complications, such as multiple pregnancy and ovarian hyperstimulation syndrome.


Although multiple follicle development will improve chances of a pregnancy, ovarian stimulation should be discontinued or conception prevented when chances of complications, that is, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS), are too high.




Overview of Existing Evidence


Prevention of Multifollicular Growth


In general, it can be stated that the risk of complications in ovulation induction can be reduced by an individualized treatment schedule, frequent treatment monitoring, and strict cancellation criteria (LOE 4).


GnRH


In WHO 1 anovulation with intact pituitary function, administration of pulsatile GnRH-agonist can restore ovulation (Chapter 14). Although the hormonal feedback loop between pituitary and ovaries remains functional, chances of multifollicular growth and concomitant complications are low (LOE 3). In a relatively large study population, multiple pregnancy rate was 3.2%, and no OHSS was reported (1).


Anti-Estrogens/Aromatase Inhibitors


Possibilities for prevention of multifollicular development during ovulation induction in WHO 2 anovulation using anti-estrogens or aromatase inhibitors are limited: These drugs are administered mostly from day 3 to day 7 after the start of a spontaneous or progestogen-induced withdrawal bleeding. The effect of this treatment can only be determined afterwards, so there is no correction possible during the treatment cycle. Therefore, treatment is started with a low daily dose, which may be increased in a following treatment cycle in case of absence of adequate ovarian response. Although reported chances on complications after ovulation induction with anti-estrogens or aromatase inhibitors are low (LOE 3), one could accept this as a calculated risk without monitoring or decide to prevent conception in case of multi-follicular development during ultrasound or serum estrogen monitoring (Chapters 24 and 25).


Gonadotropins (FSH)


Gonadotropins may be used for ovulation induction in WHO 1 and WHO 2 anovulation. The extended half-life of FSH makes it hard to predict how many follicles are going to reach the dominant status, and sometimes, daily ovarian ultrasound monitoring is required to adjust the treatment dosage before multifollicular development is a fact. This may result in daily hospital visits and increased patient inconvenience.


To prevent multifollicular growth, it is essential to surpass the FSH threshold for such a restricted period that only one follicle is allowed into ongoing development and dominance (2

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May 9, 2017 | Posted by in GYNECOLOGY | Comments Off on Complications of Ovarian Stimulation: Multifollicular Development

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