Mesej utama
- 'Ubat kesuburan' ialah rangkaian hormon dan ubat yang digunakan untuk membantu wanita hamil. Ulasan ini menunjukkan bahawa, dalam perbandingan dua ubat kesuburan yang digunakan secara meluas – gonadotropin dan anti-estrogen – gonadotropin mungkin meningkatkan bilangan kelahiran hidup.
- Kami mempunyai sedikit atau tiada keyakinan terhadap bukti yang membandingkan keberkesanan ubat kesuburan lain, untuk kedua-dua kelahiran hidup dan kadar kehamilan berganda (menjangkakan lebih daripada seorang bayi).
- Untuk menambahbaik bukti, kajian masa depan tentang inseminasi intrauterin (di mana sperma diletakkan terus di dalam rahim) harus membandingkan ubat kesuburan dengan plasebo (ubat dummy). Lebih banyak kajian membandingkan anti-estrogen dengan perencat aromatase (satu lagi ubat kesuburan yang digunakan secara meluas) juga diperlukan.
Apakah ketidaksuburan?
Ketidaksuburan ialah apabila seorang wanita tidak dapat hamil selepas 1 tahun (atau lebih lama) selepas hubungan seksual yang berkala, tanpa perlindungan. Kadangkala, doktor membezakan antara wanita yang lebih tua dan lebih muda, kerana kesuburan semula jadi menurun dengan usia. Sesetengah penjagaan kesihatan merawat wanita berumur 35 tahun ke atas untuk ketidaksuburan selepas 6 bulan hubungan seks tanpa perlindungan.
Bagaimana ketidaksuburan dirawat?
Rawatan untuk ketidaksuburan bergantung kepada apa yang mungkin menyebabkannya. Ulasan kami menumpukan pada inseminasi intrauterin yang digabungkan dengan pelbagai ubat kesuburan. Ubat kesuburan berfungsi dengan menyebabkan pembebasan hormon yang mendorong ovulasi – iaitu pembebasan telur dari ovari. Inseminasi intrauterin adalah di mana sperma diletakkan terus ke dalam rahim menggunakan tiub plastik yang nipis, dan fleksibel yang dimasukkan melalui faraj dan serviks.
Terdapat banyak ubat kesuburan yang berbeza. Yang paling biasa diberikan termasuk:
- gonadotropin (hormon suntikan bermula pada awal kitaran haid untuk menyebabkan beberapa telur membesar ke saiz matang);
- perencat anti-estrogen dan aromatase (ubat oral yang digunakan untuk mencetuskan ovulasi);
- agonis dan antagonis hormon pelepas gonadotropin (GnRH) (ubat yang digunakan untuk mengawal perkembangan telur dan ovulasi).
Apakah yang kami ingin ketahui?
Kami ingin mengetahui ubat kesuburan yang mana, digabungkan dengan inseminasi intrauterin, paling berkesan, untuk wanita yang melepaskan telur semasa haid (wanita berovulasi).
Kami berminat dengan kesan ubat kesuburan pada:
- kelahiran hidup;
· kehamilan kembar;
- 'kehamilan klinikal' (ditakrifkan sebagai bukti kantung kehamilan, struktur berisi cecair di sekeliling janin, dengan degupan jantung yang positif);
- keguguran (ditakrifkan sebagai kehilangan kehamilan dalam tempoh 12 minggu pertama);
- sindrom hiperstimulasi ovari (OHSS, keadaan di mana hormon berlebihan boleh merangsang ovari, membawa kepada pelbagai komplikasi); dan
- kehamilan ektopik, ditakrifkan sebagai kehamilan di luar rahim.
Apa yang kami buat?
Kami mencari kajian yang membandingkan ubat kesuburan yang berbeza untuk wanita berovulasi yang menjalani inseminasi intrauterin.
Kami membandingkan dan merumuskan keputusan kajian, dan menilai keyakinan kami terhadap bukti, berdasarkan faktor-faktor seperti kaedah dan saiz kajian.
Apa yang kami temui?
Kami menemui 82 kajian, melibatkan 12,614 wanita. Wanita berumur antara 18 hingga 44 tahun. Lebih daripada dua pertiga (57) kajian memasukkan wanita atau pasangan dengan ketidaksuburan yang tidak dapat dijelaskan (ketiadaan punca ketidaksuburan yang jelas), ketidaksuburan lelaki, endometriosis (keadaan yang menyakitkan apabila tisu yang serupa dengan lapisan rahim tumbuh di luar rahim), atau lebih daripada satu daripada faktor ini.
Kajian telah dijalankan di 17 negara di seluruh dunia, dengan lebih separuh dijalankan di India, Iran, Itali, Sepanyol dan Amerika Syarikat.
Terdapat lebih daripada 20 perbandingan berbeza antara pelbagai ubat kesuburan.
Hanya sekitar satu perlima (17) kajian melaporkan maklumat tentang kadar kelahiran hidup.
Keputusan utama
Gonadotropin berbanding anti-estrogen (13 kajian): mungkin meningkatkan peluang kelahiran hidup. Jika peluang kelahiran hidup berikutan anti-estrogen diandaikan 22.8%, peluang selepas gonadotropin adalah antara 23.7% dan 34.6%.
Kami tidak tahu sama ada gonadotropin membuat sebarang perbezaan kepada kadar kehamilan berganda.
Perencat aromatase berbanding anti-estrogen (8 kajian)
Kami tidak tahu sama ada perencat aromatise membuat apa-apa perbezaan kepada:
· kadar kelahiran hidup; atau
· kadar kehamilan berganda.
Gonadotropin ditambah antagonis GnRH berbanding gonadotropin sahaja (14 kajian)
Kami tidak tahu sama ada gonadotropin ditambah antagonis GnRH membuat apa-apa perbezaan kepada:
· kadar kelahiran hidup; atau
· kadar kehamilan berganda.
Perencat aromatase berbanding gonadotropin (6 kajian): boleh mengurangkan peluang kelahiran hidup. Jika peluang kelahiran hidup berikutan gonadotropin diandaikan 31.9%, peluang selepas perencat aromatase adalah antara 13.7% dan 25%.
Kami tidak tahu sama ada perencat aromatase membuat apa-apa perbezaan kepada kadar kehamilan berganda.
Perencat aromatase ditambah gonadotropin berbanding anti-estrogen ditambah gonadotropin (8 kajian):
Kami tidak tahu sama ada perencat aromatase ditambah gonadotropin membuat apa-apa perbezaan kepada:
· kadar kelahiran hidup; atau
· kadar kehamilan berganda.
Apakah batasan bukti?
Keyakinan terhadap bukti adalah dari sangat rendah hingga sederhana. Lebih daripada tiga perempat kajian mempunyai kelemahan dalam kaedah mereka yang boleh menjejaskan kebolehpercayaan keputusan mereka, dan kebanyakan kajian adalah kecil.
Sejauh mana bukti ini terkini?
Bukti adalah terkini sehingga November 2020.
Based on the available results, gonadotropins probably improve cumulative live birth rate compared with anti-oestrogens (moderate-certainty evidence). Gonadotropins may also improve cumulative live birth rate when compared with aromatase inhibitors (low-certainty evidence). From the available data, there is no convincing evidence that aromatase inhibitors lead to higher live birth rates compared to anti-oestrogens. None of the agents compared lead to significantly higher multiple pregnancy rates. Based on low-certainty evidence, there does not seem to be a role for different combined therapies, nor for adding GnRH agonists or GnRH antagonists in IUI programs.
Intrauterine insemination (IUI), combined with ovarian stimulation (OS), has been demonstrated to be an effective treatment for infertile couples. Several agents for ovarian stimulation, combined with IUI, have been proposed, but it is still not clear which agents for stimulation are the most effective. This is an update of the review, first published in 2007.
To assess the effects of agents for ovarian stimulation for intrauterine insemination in infertile ovulatory women.
We searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trial registers from their inception to November 2020. We performed reference checking and contacted study authors and experts in the field to identify additional studies.
We included truly randomised controlled trials (RCTs) that compared different agents for ovarian stimulation combined with IUI for infertile ovulatory women concerning couples with unexplained infertility. mild male factor infertility and minimal to mild endometriosis.
We used standard methodological procedures recommended by Cochrane.
In this updated review, we have included a total of 82 studies, involving 12,614 women. Due to the multitude of comparisons between different agents for ovarian stimulation, we highlight the seven most often reported here.
Gonadotropins versus anti-oestrogens (13 studies)
For live birth, the results of five studies were pooled and showed a probable improvement in the cumulative live birth rate for gonadotropins compared to anti-oestrogens (odds ratio (OR) 1.37, 95% confidence interval (CI) 1.05 to 1.79; I 2 = 30%; 5 studies, 1924 participants; moderate-certainty evidence). This suggests that if the chance of live birth following anti-oestrogens is assumed to be 22.8%, the chance following gonadotropins would be between 23.7% and 34.6%. The pooled effect of seven studies revealed that we are uncertain whether gonadotropins lead to a higher multiple pregnancy rate compared with anti-oestrogens (OR 1.58, 95% CI 0.60 to 4.17; I 2 = 58%; 7 studies, 2139 participants; low-certainty evidence).
Aromatase inhibitors versus anti-oestrogens (8 studies)
One study reported live birth rates for this comparison. We are uncertain whether aromatase inhibitors improve live birth rate compared with anti-oestrogens (OR 0.75, CI 95% 0.51 to 1.11; 1 study, 599 participants; low-certainty evidence). This suggests that if the chance of live birth following anti-oestrogens is 23.4%, the chance following aromatase inhibitors would be between 13.5% and 25.3%. The results of pooling four studies revealed that we are uncertain whether aromatase inhibitors compared with anti-oestrogens lead to a higher multiple pregnancy rate (OR 1.28, CI 95% 0.61 to 2.68; I 2 = 0%; 4 studies, 1000 participants; low-certainty evidence).
Gonadotropins with GnRH (gonadotropin-releasing hormone) agonist versus gonadotropins alone (4 studies)
No data were available for live birth. The pooled effect of two studies revealed that we are uncertain whether gonadotropins with GnRH agonist lead to a higher multiple pregnancy rate compared to gonadotropins alone (OR 2.53, 95% CI 0.82 to 7.86; I 2 = 0; 2 studies, 264 participants; very low-certainty evidence).
Gonadotropins with GnRH antagonist versus gonadotropins alone (14 studies)
Three studies reported live birth rate per couple, and we are uncertain whether gonadotropins with GnRH antagonist improve live birth rate compared to gonadotropins (OR 1.5, 95% CI 0.52 to 4.39; I 2 = 81%; 3 studies, 419 participants; very low-certainty evidence). This suggests that if the chance of a live birth following gonadotropins alone is 25.7%, the chance following gonadotropins combined with GnRH antagonist would be between 15.2% and 60.3%. We are also uncertain whether gonadotropins combined with GnRH antagonist lead to a higher multiple pregnancy rate compared with gonadotropins alone (OR 1.30, 95% CI 0.74 to 2.28; I 2 = 0%; 10 studies, 2095 participants; moderate-certainty evidence).
Gonadotropins with anti-oestrogens versus gonadotropins alone (2 studies)
Neither of the studies reported data for live birth rate. We are uncertain whether gonadotropins combined with anti-oestrogens lead to a higher multiple pregnancy rate compared with gonadotropins alone, based on one study (OR 3.03, 95% CI 0.12 to 75.1; 1 study, 230 participants; low-certainty evidence).
Aromatase inhibitors versus gonadotropins (6 studies)
Two studies revealed that aromatase inhibitors may decrease live birth rate compared with gonadotropins (OR 0.49, 95% CI 0.34 to 0.71; I 2 =0%; 2 studies, 651 participants; low-certainty evidence). This suggests that if the chance of a live birth following gonadotropins alone is 31.9%, the chance of live birth following aromatase inhibitors would be between 13.7% and 25%. We are uncertain whether aromatase inhibitors compared with gonadotropins lead to a higher multiple pregnancy rate (OR 0.69, 95% CI 0.06 to 8.17; I 2 =77%; 3 studies, 731 participants; very low-certainty evidence).
Aromatase inhibitors with gonadotropins versus anti-oestrogens with gonadotropins (8 studies)
We are uncertain whether aromatase inhibitors combined with gonadotropins improve live birth rate compared with anti-oestrogens plus gonadotropins (OR 0.99, 95% CI 0.3 8 to 2.54; I 2 = 69%; 3 studies, 708 participants; very low-certainty evidence). This suggests that if the chance of a live birth following anti-oestrogens plus gonadotropins is 13.8%, the chance following aromatase inhibitors plus gonadotropins would be between 5.7% and 28.9%. We are uncertain of the effect of aromatase inhibitors combined with gonadotropins compared to anti-oestrogens combined with gonadotropins on multiple pregnancy rate (OR 1.31, 95% CI 0.39 to 4.37; I 2 = 0%; 5 studies, 901 participants; low-certainty evidence).
Diterjemahkan oleh Rahimah Zakaria (Universiti Sains Malaysia). Disunting oleh Shazlin Shaharudin (Universiti Sains Malaysia). Untuk sebarang pertanyaan berkaitan terjemahan ini, sila hubungi cochrane@rcsiucd.edu.my